• 主题
高级搜索  >
历史搜索 清空历史

您现在的位置：首页>美国卫生研究院文献>American Journal of Physiology - Renal Physiology

期刊信息

  • 期刊名称：

    -

  • 刊频： Twice monthly, Jan. 2012-
  • NLM标题： Am J Physiol Renal Physiol
  • iso缩写： -
  • ISSN： -

年度选择

更多>>

  • 排序：
  • 显示：
  • 每页：
全选（0）
<1/6>
共112条结果
  • 1.

    【2hr】Rethinking glomerular basement membrane thickening in diabetic nephropathy: adaptive or pathogenic?

    包量

    机译 对糖尿病性肾病中肾小球基底膜增厚的反思：适应性还是病原性？
    • 作者：Caroline B. Marshall
    • 刊名：American Journal of Physiology - Renal Physiology
    • 2016年第5期
    摘要：Diabetic nephropathy (DN) is the leading cause of chronic kidney disease in the United States and is a major cause of cardiovascular disease and death. DN develops insidiously over a span of years before clinical manifestations, including microalbuminuria and declining glomerular filtration rate (GFR), are evident. During the clinically silent period, structural lesions develop, including glomerular basement membrane (GBM) thickening, mesangial expansion, and glomerulosclerosis. Once microalbuminuria is clinically apparent, structural lesions are often considerably advanced, and GFR decline may then proceed rapidly toward end-stage kidney disease. Given the current lack of sensitive biomarkers for detecting early DN, a shift in focus toward examining the cellular and molecular basis for the earliest structural change in DN, i.e., GBM thickening, may be warranted. Observed within one to two years following the onset of diabetes, GBM thickening precedes clinically evident albuminuria. In the mature glomerulus, the podocyte is likely key in modifying the GBM, synthesizing and assembling matrix components, both in physiological and pathological states. Podocytes also secrete matrix metalloproteinases, crucial mediators in extracellular matrix turnover. Studies have shown that the critical podocyte-GBM interface is disrupted in the diabetic milieu. Just as healthy podocytes are essential for maintaining the normal GBM structure and function, injured podocytes likely have a fundamental role in upsetting the balance between the GBM’s synthetic and degradative pathways. This article will explore the biological significance of GBM thickening in DN by reviewing what is known about the GBM’s formation, its maintenance during health, and its disruption in DN.
  • 2.

    【2hr】Carbonic anhydrase II binds to and increases the activity of the epithelial sodium-proton exchanger, NHE3

    包量

    机译 碳酸酐酶II结合并增加上皮钠质子交换器NHE3的活性
    摘要：Two-thirds of sodium filtered by the renal glomerulus is reabsorbed from the proximal tubule via a sodium/proton exchanger isoform 3 (NHE3)-dependent mechanism. Since sodium and bicarbonate reabsorption are coupled, we postulated that the molecules involved in their reabsorption [NHE3 and carbonic anhydrase II (CAII)] might physically and functionally interact. Consistent with this, CAII and NHE3 were closely associated in a renal proximal tubular cell culture model as revealed by a proximity ligation assay. Direct physical interaction was confirmed in solid-phase binding assays with immobilized CAII and C-terminal NHE3 glutathione-S-transferase fusion constructs. To assess the effect of CAII on NHE3 function, we expressed NHE3 in a proximal tubule cell line and measured NHE3 activity as the rate of intracellular pH recovery, following an acid load. NHE3-expressing cells had a significantly greater rate of intracellular pH recovery than controls. Inhibition of endogenous CAII activity with acetazolamide significantly decreased NHE3 activity, indicating that CAII activates NHE3. To ascertain whether CAII binding per se activates NHE3, we expressed NHE3 with wild-type CAII, a catalytically inactive CAII mutant (CAII-V143Y), or a mutant unable to bind other transporters (CAII-HEX). NHE3 activity increased upon wild-type CAII coexpression, but not in the presence of the CAII V143Y or HEX mutant. Together these studies support an association between CAII and NHE3 that alters the transporter’s activity.
  • 3.

    【2hr】Proximal tubular NHEs: sodium, protons and calcium?

    包量

    机译 近端肾小管NHE：钠，质子和钙？
    摘要：Na+/H+ exchange activity in the apical membrane of the proximal tubule is fundamental to the reabsorption of Na+ and water from the filtrate. The role of this exchange process in bicarbonate reclamation and, consequently, the maintenance of acid-base homeostasis has been appreciated for at least half a century and remains a pillar of renal tubular physiology. More recently, apical Na+/H+ exchange, mediated by Na+/H+ exchanger isoform 3 (NHE3), has been implicated in proximal tubular reabsorption of Ca2+ and Ca2+ homeostasis in general. Overexpression of NHE3 increased paracellular Ca2+ flux in a proximal tubular cell model. Consistent with this observation, mice with genetic deletion of Nhe3 have a noticable renal Ca2+ leak. These mice also display decreased intestinal Ca2+ uptake and osteopenia. This review highlights the traditional roles of proximal tubular Na+/H+ exchange and summarizes recent novel findings implicating the predominant isoform, NHE3, in Ca2+ homeostasis.
  • 4.

    【2hr】Activation of the Ca2+-sensing receptor increases renal claudin-14 expression and urinary Ca2+ excretion

    包量

    机译 Ca2 +感应受体的激活增加了肾脏claudin-14的表达和尿中Ca2 +的排泄
    摘要：Kidney stones are a prevalent clinical condition imposing a large economic burden on the health-care system. Hypercalciuria remains the major risk factor for development of a Ca2+-containing stone. The kidney’s ability to alter Ca2+ excretion in response to changes in serum Ca2+ is in part mediated by the Ca2+-sensing receptor (CaSR). Recent studies revealed renal claudin-14 (Cldn14) expression localized to the thick ascending limb (TAL) and its expression to be regulated via the CaSR. We find that Cldn14 expression is increased by high dietary Ca2+ intake and by elevated serum Ca2+ levels induced by prolonged 1,25-dihydroxyvitamin D3 administration. Consistent with this, activation of the CaSR in vivo via administration of the calcimimetic cinacalcet hydrochloride led to a 40-fold increase in Cldn14 mRNA. Moreover, overexpression of Cldn14 in two separate cell culture models decreased paracellular Ca2+ flux by preferentially decreasing cation permeability, thereby increasing transepithelial resistance. These data support the existence of a mechanism whereby activation of the CaSR in the TAL increases Cldn14 expression, which in turn blocks the paracellular reabsorption of Ca2+. This molecular mechanism likely facilitates renal Ca2+ losses in response to elevated serum Ca2+. Moreover, dys-regulation of the newly described CaSR-Cldn14 axis likely contributes to the development of hypercalciuria and kidney stones.
  • 5.

    【2hr】The natriuretic and diuretic response to dopamine is maintained during rat pregnancy

    包量

    机译 大鼠怀孕期间维持对多巴胺的利钠和利尿反应
    摘要：During pregnancy, there is a marked plasma volume expansion due to renal sodium retention. Pregnant rats exhibit a blunted response to natriuretic stimuli that signal via cGMP, and expression and activity of the cGMP phosphodiesterase PDE-5 are upregulated in the inner medullary collecting duct during pregnancy. Here, we tested the hypothesis that the natriuretic response to a cAMP agonist, dopamine, is maintained during pregnancy. Anesthetized pregnant (day 16) and age-matched virgin Sprague-Dawley rats were used to determine whether dopamine-cAMP-mediated natriuresis remains intact in pregnant rats. Blood pressure, renal clearances of inulin and p-aminohippuric acid, and excretion of sodium were measured during baseline and dopamine infusion periods. Pregnant rats had a lower blood pressure and hematocrit at baseline than their age-matched virgin counterparts. Dopamine infusion decreased blood pressure and increased glomerular filtration rate and renal plasma flow in virgin but not pregnant rats. Dopamine infusion also increased urine volume, sodium excretion, and the fractional excretion of sodium to a similar extent in virgin and pregnant rats. These results indicate that a cAMP-mediated natriuresis and diuresis (stimulated by dopamine) persists in pregnant rats.
  • 6.

    【2hr】An Androgen-Inducible Proximal Tubule-Specific Cre-Recombinase Transgenic Model

    包量

    机译 雄激素诱导的近端小管特异性Cre重组酶转基因模型
    摘要：To facilitate the study of renal proximal tubules, we generated a transgenic mouse strain expressing an improved Cre-recombinase (iCre) under the control of the kidney androgen regulated protein (KAP) promoter. The transgene was expressed in the kidney of male mice but not in female mice. Treatment of female transgenic mice with androgen induced robust expression of the transgene in the kidney. We confirmed the presence of Cre-recombinase activity and the cell-specificity by breeding the KAP2-iCRE mice with ROSA26 reporter mice. X-gal staining of kidney sections from male double transgenic mice showed robust staining in the epithelial cells of renal proximal tubules. β-galactosidase staining in female mice became evident in proximal tubules after administration of androgen. This model of inducible Cre-recombinase in the renal proximal tubule should provide a novel useful tool for studying the physiological significance of genes expressed in the renal proximal tubule. This has advantages of other current models where cre-recombinase expression is constitutive, not inducible.
  • 7.

    【2hr】Signaling Pathways Modulated by Fish Oil in Salt-Sensitive Hypertension

    包量

    机译 鱼油调节盐敏感性高血压的信号通路
    摘要：Although many studies have indicated that fish oil (FO) improves cardiovascular risk factors and reduces histopathologic manifestations of injury in experimental renal injury models, potential mechanisms underlying this protective effect have not been adequately defined. The objective of this study was to identify potential signaling pathways that confer protection in the Dahl rat model of salt-sensitive hypertension. Male Dahl salt-sensitive rats (n=10 per group) were provided with formulated diets containing 8% NaCl, 20% protein, and 25% FO or 25% corn oil (CO) for 28 days. FO reduced blood pressure (-11% at 4 weeks, P<0.05), urine protein excretion (-45% at 4 weeks, P<0.05), plasma cholesterol and triglyceride levels (-54%, P<0.001 and -58%, P<0.05), and histopathologic manifestations of renal injury, including vascular hypertrophy, segmental and global glomerular sclerosis, interstitial fibrosis, and tubular atrophy. Interstitial inflammation was significantly reduced by FO (-32%, P<0.001), as assessed by quantitative analysis of ED1-positive cells in sections of renal cortex. FO reduced tubulointerstitial proliferative activity, as assessed by Western blot analysis of cortical homogenates for PCNA (-51%, P<0.01) and quantitative analysis of Mib-1 stained sections of renal cortex (-42%, P<0.001). Decreased proliferative activity was associated with reduced p-ERK expression (-37%, P<0.005) and NF-κB activation (-42%, P<0.05). FO reduced COX-2 expression (-63%, P<0.01) and membrane translocation of the NADPH oxidase subunits p47phox and p67phox (-26% and -34%, P<0.05). We propose that FO ameliorates renal injury in Dahl salt-sensitive rats through inhibition of ERK, decreased NF-κB activation, inhibition of COX-2 expression, and decreased NADPH oxidase activation.
  • 8.

    【2hr】Smad ubiquitination regulatory factor-2 in the fibrotic kidney: regulation, target specificity and functional implication

    包量

    机译 纤维化肾脏中的Smad泛素化调节因子2：调节，靶标特异性和功能暗示
    摘要：Smad ubiquitination regulatory factor-2 (Smurf2) is an E3 ubiqutin ligase that plays a pivotal role in regulating the TGF-β signaling via selectively targeting key components of Smad pathway for degradation. In this study, we have investigated the regulation of Smurf2 expression, its target specificity and the functional implication of its induction in the fibrotic kidney. Immunohistochemical staining revealed that Smurf2 was upregulated specifically in renal tubules of kidney biopsies from patients with various nephropathies. In vitro, Smurf2 mRNA and protein were induced in human proximal tubular epithelial cells (HKC-8) upon TGF-β1 stimulation. Ectopic expression of Smurf2 was sufficient to reduce the steady-state levels of Smad2, but not Smad1, Smad3, Smad4 and Smad7, in HKC-8 cells. Interestingly, Smurf2 was also able to down-regulate the Smad transcriptional corepressors SnoN, Ski and TGIF. Inhibition of the proteasomal pathway prevented Smurf2-mediated down-regulation of Smad2 and Smad corepressors. Functionally, over-expression of Smurf2 enhanced the transcription of TGF-β-responsive promoter and augmented the TGF-β1-mediated E-cadherin suppression, as well as fibronectin and type I collagen induction in HKC-8 cells. These results indicate that Smurf2 specifically targets both positive and negative Smad regulators for destruction in tubular epithelial cells, thereby providing a complex fine-tuning of the TGF-β signaling. It appears that dysregulation of Smurf2 could contribute to an aberrant TGF-β/Smad signaling in the pathogenesis of kidney fibrosis.
  • 9.

    【2hr】Determination of plasma and urinary angiotensinogen levels in rodents by newly developed ELISA

    包量

    机译 通过最新开发的ELISA测定啮齿动物的血浆和尿中血管紧张素原水平
    摘要：We recently reported that urinary excretion rates of angiotensinogen provide a specific index of the intrarenal renin-angiotensin system status in angiotensin II-dependent hypertensive rats. Angiotensinogen concentrations in mouse plasma are thought to be much lower than those in rat plasma; however, detailed information is deficient due to lack of direct quantitative measurements of rodent angiotensinogen. To elucidate this issue, we have developed a quantitative method for measurement of rodent angiotensinogen using a sandwich-type ELISA. The standard curve for mouse and rat angiotensinogen exhibited a high linearity at 0.16–10 and 0.08–5 ng/ml, respectively, with correlation coefficients >0.99. While plasma angiotensinogen concentrations of male high serum IgA (HIGA) mice (IgA nephritis model animals, 1,308 ± 47 ng/ml; n = 10) were lower than those of control BALB/c mice (1,620 ± 384; n = 12), urinary angiotensinogen concentrations of HIGA mice (14.6 ± 1.5 ng/ml; n = 34) were higher than those of BALB/c mice (4.6 ± 0.1; n = 2). In a similar manner, while plasma angiotensinogen concentrations of Zucker diabetic fatty (ZDF) obese rats (type 2 diabetic model animals, 1,789 ± 50 ng/ml; n = 5) were lower than those of control ZDF lean rats (2,296 ± 47; n = 5), urinary angiotensinogen concentrations of ZDF obese rats (88.2 ± 11.4 ng/ml; n = 15) were higher than those of ZDF lean rats (31.3 ± 1.9; n = 15). These data indicate that plasma and urinary angiotensinogen concentrations are less in mice than rats. However, these data suggest that urinary angiotensinogen levels are different from plasma angiotensinogen levels in rodents. The development of rodent angiotensinogen ELISA allows quantitative comparisons in mouse and rat angiotensinogen levels in models of hypertension and cardiovascular and kidney diseases.
  • 10.

    【2hr】Calcium oxalate crystal deposition in kidneys of hypercalciuric mice with disrupted type IIa sodium-phosphate cotransporter

    包量

    机译 草酸钙晶体沉积在IIa型磷酸钠共转运蛋白受损的高钙血症小鼠肾脏中
    摘要：The most common theories about the pathogenesis of idiopathic kidney stones consider precipitation of calcium phosphate (CaP) within the kidneys critical for the development of the disease. We decided to test the hypothesis that a CaP substrate can promote the deposition of calcium oxalate (CaOx) in the kidneys. Experimental hyperoxaluria was induced by feeding glyoxylate to male mice with knockout (KO) of NaPi IIa (Npt2a), a sodium-phosphate cotransporter. Npt2a KO mice are hypercalciuric and produce CaP deposits in their renal tubules. Experimental hyperoxaluria led to CaOx crystalluria in both the hypercalciuric KO mice and the normocalciuric control B6 mice. Only the KO mice produced CaOx crystal deposits in their kidneys, but the CaOx crystals deposited separately from the CaP deposits. Perhaps CaP deposits were not available for a CaOx overgrowth. These results also validate earlier animal model observations that showed that CaP substrate is not required for renal deposition of CaOx and that other factors, such as local supersaturation, may be involved. The absence of CaOx deposition in the B6 mice despite extreme hyperoxaluria also signifies the importance of both calcium and oxalate in the development of CaOx nephrolithiasis.
  • 11.

    【2hr】LOSS OF PROSTAGLANDIN E2 RELEASE FROM IMMORTALIZED UROTHELIAL CELLS OBTAINED FROM INTERSTITIAL CYSTITS PATIENT BLADDERS

    包量

    机译 从间质性囊肿患者膀胱中获得的非正常化的上皮细胞释放前列腺素E2的损失
    摘要：Interstitial cystitis (IC) is associated with increased activated mast cell numbers in the bladder and impairment of the barrier function of the urothelium. We stimulated immortalized urothelial cells derived from the inflamed region of IC bladders (SR22A or SM28 abn) or from healthy bladders (PD07i or PD08i) with tryptase and measured phospholipase A2 (PLA2) activity and the resultant release of arachidonic acid and prostaglandin E2 (PGE2). Tryptase stimulation of either PD07i or SR22A resulted in similar increases in PLA2 activity and arachidonic acid release. However, tryptase stimulation of SR22A and SM28 abn did not result in a significant increase in PGE2 release when compared to the increase in PGE2 release from tryptase-stimulated PD07i and PD08i cells. Expression of mRNA for cyclooxygenase-2 (COX-2) and prostaglandin E synthase was lower and mRNA for 15-hydroxyprostaglandin dehydrogenase was higher in SR22A compared to PD07i, suggesting that both decreased synthesis and increased metabolism is responsible for the lack of a PGE2 response in tryptase stimulated SR22A cells. Since PGE2 is a cytoprotective eicosanoid, the failure to produce this metabolite in cells isolated from the IC bladder may represent an increased susceptibility to damage by pro-inflammatory stimuli.
  • 12.

    【2hr】Nedd4-2 isoforms ubiquitinate individual epithelial sodium channel subunits and reduce surface expression and function of the epithelial sodium channel

    包量

    机译 Nedd4-2亚型泛素化单个上皮钠通道亚基，并降低表面表达和上皮钠通道功能
    摘要：We have previously reported the existence of multiple isoforms of human Nedd4-2 (AJP Renal 2003, 285: F916). When overexpressed in M-1 collecting duct epithelia, full length Nedd4-2 (Nedd4-2), Nedd4-2 lacking the N-terminal C2 domain (Nedd4-2ΔC2) and Nedd4-2 lacking WW domains 2 and 3 (Nedd4-2ΔWW2,3) variably reduce benzamil-sensitive Na+ transport. We investigated the effect of each of the Nedd4-2 isoforms on cell-surface expression and ubiquitination of ENaC subunits. We find that αENaC when transfected alone or with β and γENaC is expressed at the cell surface and this membrane expression is variably reduced by co-expression with each of the Nedd4-2 isoforms. Nedd4-2 reduces the half-life of ENaC subunits and enhances the ubiquitination of α, β and γ ENaC subunits when expressed alone or together suggesting that each subunit is a target for Nedd4-2 mediated ubiquitination. As has been reported recently, we confirm that the surface expressed pool of ENaC is multi-ubiquitinated. Inhibitors of the proteasome increase ubiquitination of ENaC subunits and stimulate Na+ transport in M-1 cells consistent with a role for the ubiquitin-proteasome pathway in regulating Na+ transport in the collecting duct.
  • 13.

    【2hr】Renal medullary ETB receptors produce diuresis and natriuresis via NOS1

    包量

    机译 肾髓质ETB受体通过NOS1产生利尿和利尿作用
    摘要：Endothelin-1 (ET-1) plays an important role in the regulation of salt and water excretion in the kidney. Considerable in vitro evidence suggests that the renal medullary ETB receptor mediates ET-1-induced inhibition of electrolyte reabsorption by stimulating nitric oxide (NO) production. The present study was conducted to test the hypothesis that NO synthase 1 (NOS1) and protein kinase G (PKG) mediate the diuretic and natriuretic effects of ETB receptor stimulation in vivo. Infusion of the ETB receptor agonist, sarafotoxin S6c (S6c: 0.45 μg/kg/h), into the renal medulla of anesthetized, male Sprague-Dawley rats markedly increased the urine flow (UV) and urinary sodium excretion (UNaV) by 67 and 120%, respectively. This was associated with an increase in medullary cGMP content, but did not affect blood pressure. In addition, S6c-induced diuretic and natriuretic responses were absent in ETB receptor-deficient rats. Co-infusion of NG-propyl-l-arginine (10 μg/kg/h), a selective NOS1 inhibitor suppressed S6c-induced increases in UV, UNaV and medullary cGMP concentrations. Rp-8-Br-PET-cGMPS (10 μg/kg/h) or DT-3 (18 μg/kg/h), a PKG inhibitor, also inhibited S6c-induced increases in UV and UNaV. These results demonstrate that renal medullary ETB receptor activation induces diuretic and natriuretic responses through a NOS1, cGMP and PKG pathway.
  • 14.

    【2hr】Chloroquine and inhibition of Toll-like receptor 9 protect from sepsis-induced acute kidney injury

    包量

    机译 氯喹和抑制Toll样受体9可以防止败血症引起的急性肾脏损伤
    摘要：Mortality from sepsis has remained high despite recent advances in supportive and targeted therapies. Toll-like receptors (TLRs) sense bacterial products and stimulate pathogenic innate immune responses. Mice deficient in the common adapter protein MyD88, downstream from most TLRs, have reduced mortality and acute kidney injury (AKI) from polymicrobial sepsis. However, the identity of the TLR(s) responsible for the host response to polymicrobial sepsis is unknown. Here, we show that chloroquine, an inhibitor of endocytic TLRs (TLR3, 7, 8, 9), improves sepsis-induced mortality and acute kidney injury in a clinically relevant polymicrobial sepsis mouse model, even when administered 6h after the septic insult. Chloroquine administration attenuated the decline in renal function, splenic apoptosis, serum markers of damage to other organs, and prototypical serum pro- and anti-inflammatory cytokines TNF-alpha and IL-10. An oligodeoxynucleotide inhibitor (H154) of TLR9 and TLR9-deficient mice mirror the actions of chloroquine in all functional parameters that we tested. In addition, chloroquine decreased TLR9 protein abundance in spleen, further suggesting that TLR9 signaling may be a major target for the protective actions of chloroquine. Our findings indicate that chloroquine improves survival by inhibiting multiple pathways leading to polymicrobial sepsis, and that chloroquine and TLR9 inhibitors represent viable broad-spectrum and targeted therapeutic strategies, respectively, that are promising candidates for further clinical development.
  • 15.

    【2hr】Angiotensin II stimulates elution of Na-K-ATPase from a digoxin-affinity column by increasing the kinetic response to ligands that trigger the decay of E2-P

    包量

    机译 血管紧张素II通过增加对触发E2-P衰变的配体的动力学响应来刺激地高辛亲和柱上的Na-K-ATPase洗脱
    摘要：We earlier observed that treating rat proximal tubules with concentrations of angiotensin II (ANG II) that directly stimulate Na-K-ATPase activity changed how Na-K-ATPase subsequently eluted from an ouabain-affinity column. In this study we tested whether ANG II increases the rate of elution in response to ligands that trigger the decay of E2-P, which implies a change in functional properties of Na-K-ATPase, or by decreasing the amount subsequently eluted with SDS, which suggests a change in how Na-K-ATPase interacts with other proteins. We utilized a new digoxin-affinity column and novel lines of opossum kidney (OK) cells that coexpress the rat AT1a receptor and either the wild-type rat α1-isoform of Na-K-ATPase or a truncation mutant missing the first 32 amino acids of its NH2 terminus. We characterized how rat kidney microsomes bind to and elute from the digoxin-affinity column and demonstrated that they are heterogeneous in the rate at which they release digoxin in response to ligands that trigger the decay of E2-P. Incubating OK cells with ANG II stimulated the ensuing elution of wild-type rat α1-subunit by increasing the kinetic response to ligands that cause a decay of E2-P without affecting the amount later eluted with SDS. In contrast, ANG II had no effect on the kinetic response of the truncation mutant but decreased the amount eluted with SDS. These data suggest that ANG II regulates both the kinetic properties of Na-K-ATPase and its interaction with other proteins by a mechanism(s) involving its NH2 terminus.
  • 16.

    【2hr】Netrin-1 and kidney injury. I. Netrin-1 protects against ischemia-reperfusion injury of the kidney

    包量

    机译 Netrin-1和肾脏损伤。 I. Netrin-1保护肾脏免受缺血再灌注损伤
    摘要：Endogenous mechanisms exist to limit inflammation. One such molecule is netrin. This study examined the impact of ischemia-reperfusion (I/R) on netrin expression and the role of netrin in preventing renal inflammation and injury. All three isoforms of netrin (1, 3, and 4) are expressed in normal kidney. I/R significantly downregulated netrin-1 and -4 mRNA expression, whereas expression of netrin-3 was moderately upregulated at 24 h of reperfusion. The netrin receptor UNC5B mRNA increased at 3 h and but decreased at later time points. Expression of a second netrin receptor, DCC, was not altered significantly. I/R was associated with dramatic changes in netrin-1 protein abundance and localization. Netrin-1 protein levels increased between 3 and 24 h after reperfusion. Immunolocalization showed an interstitial distribution of netrin-1 in sham-operated kidneys which colocalized with Von Willebrand Factor suggesting the presence of netrin-1 in peritubular capillaries. After I/R, interstitial netrin-1 expression decreased and netrin-1 appeared in tubular epithelial cells. By 72 h after reperfusion, netrin-1 reappeared in the interstitium while tubular epithelial staining decreased significantly. Downregulation of netrin-1 in the interstitium corresponded with increased MCP-1 and IL-6 expression and infiltration of leukocytes into the reperfused kidney. Administration of recombinant netrin-1 significantly improved kidney function (blood urea nitrogen: 161 ± 7 vs. 104 ± 24 mg/dl, creatinine: 1.3 ± 0.07 vs. 0.75 ± 0.16 mg/dl, P < 0.05 at 24 h) and reduced tubular damage and leukocyte infiltration in the outer medulla. These results suggest that downregulation of netrin-1 in vascular endothelial cells may promote endothelial cell activation and infiltration of leukocytes into the kidney thereby enhancing tubular injury.
  • 17.

    【2hr】Inhibitory and excitatory perigenital-to-bladder spinal reflexes in the cat

    包量

    机译 猫的抑制性和兴奋性生殖器至膀胱脊柱反射
    摘要：This study revealed that in awake chronic spinal cord-injured (SCI) cats reflexes from perigenital skin area to the bladder can be either inhibitory or excitatory. Electrical perigenital stimulation at frequencies between 5 and 7 Hz significantly inhibited large-amplitude rhythmic reflex bladder activity, whereas frequencies between 20 and 40 Hz induced large-amplitude bladder contractions even at low bladder volumes when reflex bladder activity was absent. Both inhibitory and excitatory effects were enhanced as the stimulation intensity increased (5–30 V, 0.2-ms pulse width). During cystometrograms, the inhibitory stimulation (7 Hz) significantly increased the micturition volume threshold 35 ± 13% above the control volume, while the excitatory stimulation (30 Hz) significantly reduced the threshold 21 ± 3%. Mechanical perigenital stimulation applied by repeated light stroking of the perigenital skin with a cotton swab only induced an excitatory effect on the bladder. Both electrical and mechanical perigenital stimuli induced large-amplitude (>30 cmH2O) bladder contractions that were relatively consistent over a range of bladder volumes (10–90% of the capacity). However, the excitatory electrical stimulation only induced bladder contractions lasting on average 42.2 ± 3.9 s, but the mechanical stimulation induced bladder contractions that lasted as long as the stimulation continued (2–3 min). Excitatory electrical or mechanical perigenital stimulation also induced poststimulus voiding. The ability to either inhibit or excite the bladder by noninvasive methods could significantly transform the current clinical management of bladder function after SCI.
  • 18.

    【2hr】Akt activation improves oxidative phosphorylation in renal proximal tubular cells following nephrotoxicant injury

    包量

    机译 Akt激活可改善肾毒性损伤后肾近端小管细胞的氧化磷酸化
    摘要：Previously, we showed that protein kinase B (Akt) activation increases intracellular ATP levels and decreases necrosis in renal proximal tubular cells (RPTC) injured by the nephrotoxicant S-(1, 2-dichlorovinyl)-L-cysteine (DCVC) (Shaik ZP, Fifer EK, Nowak G. Am J Physiol Renal Physiol 292: F292–F303, 2007). This study examined the role of Akt in improving mitochondrial function in DCVC-injured RPTC. Our data show a novel observation that phosphorylated (active) Akt is localized in mitochondria of noninjured RPTC, both in mitoplasts and the mitochondrial outer membrane. Mitochondrial levels of active Akt decreased in nephrotoxicant-injured RPTC, and this decrease was associated with mitochondrial dysfunction. DCVC decreased basal, uncoupled, and state 3 respirations; ATP production; activities of complexes I, II, and III; the mitochondrial membrane potential (ΔΨm); and F0F1-ATPase activity. Expressing constitutively active Akt in DCVC-injured RPTC increased the levels of phosphorylated Akt in mitochondria, reduced the decreases in basal and uncoupled respirations, increased complex I-coupled state 3 respiration and ATP production, enhanced activities of complex I, complex III, and F0F1-ATPase, and improved ΔΨm. In contrast, inhibiting Akt activation by expressing dominant negative (inactive) Akt or using 20 μM exacerbated decreases in electron transport rate, state 3 respiration, ATP production, ΔΨm, and activities of complex I, complex III, and F0F1-ATPase. In conclusion, our data show that Akt activation promotes mitochondrial respiration and ATP production in toxicant-injured RPTC by 1) improving integrity of the respiratory chain and maintaining activities of complex I and complex III, 2) reducing decreases in ΔΨm, and 3) restoring F0F1-ATPase activity.
  • 19.

    【2hr】In vivo regulation of AT1a receptor-mediated intracellular uptake of [125I]Val5-ANG II in the kidneys and adrenals of AT1a receptor-deficient mice

    包量

    机译 AT1a受体缺陷小鼠的肾脏和肾上腺中AT1a受体介导的[125I] Val5-ANG II细胞内摄取的体内调节
    • 作者：Xiao C. LiJia L. Zhuo
    • 刊名：American Journal of Physiology - Renal Physiology
    • 2008年第2期
    摘要：Using type 1a angiotensin receptor (AT1a) receptor-deficient (Agtr1a−/−) mice and in vivo autoradiography, we tested the hypothesis that intracellular uptake of ANG II in the kidney and adrenal glands is primarily mediated by AT1a receptors and that the response is regulated by prevailing endogenous ANG II. After pretreatment of wild-type (Agtr1a+/+) and Agtr1a−/− mice (n = 6–9 each group) with or without captopril (25 mg·kg−1 ·day−1) or losartan (10 mg·kg−1 ·day−1) for 2 wk, [125I]Val5-ANG II was infused for 60 min. Intracellular uptake of [125I]Val5-ANG II was determined by quantitative in vivo autoradiography after washout of circulating [125I]Val5-ANG II. Basal intracellular ANG II levels were 65% lower in the kidney (P < 0.001), but plasma ANG II levels were threefold higher, in Agtr1a−/− than wild-type mice (P < 0.01). Although plasma [125I]Val5-ANG II levels were similar, urinary excretion of [125I]Val5-ANG II was fourfold higher in Agtr1a−/− mice (P < 0.001). By contrast, intracellular [125I]Val5-ANG II levels were ~80% lower in the kidney and adrenal glands of Agtr1a−/− mice (P < 0.01). Captopril decreased endogenous plasma and renal ANG II levels (P < 0.01) but increased intracellular uptake of [125I]Val5-ANG II in the kidney and adrenal glands of wild-type and Agtr1a−/− mice (P < 0.01). Losartan largely blocked renal and adrenal uptake of [125I]Val5-ANG II in wild-type and Agtr1a−/− mice. Thus 80% of intracellular ANG II uptake in the kidney and adrenal glands is mediated by AT1a receptors, whereas AT1b receptor- and other non-receptor-mediated mechanisms account for 20% of the response. Our results suggest that AT1a receptor-mediated uptake of extracellular ANG II may play a physiological role in the kidney and adrenal glands.
  • 20.

    【2hr】Purinergic receptors contribute to early mesangial cell transformation and renal vessel hypertrophy during angiotensin II-induced hypertension

    包量

    机译 嘌呤能受体有助于血管紧张素II诱发的高血压期间早期系膜细胞转化和肾血管肥大
    摘要：Chronic ANG II infusions lead to increases in intrarenal ANG II levels, hypertension, and tissue injury. Increased blood pressure also elicits increases in renal interstitial fluid (RIF) ATP concentrations that stimulate cell proliferation. We evaluated the contribution of purinergic receptor activation to ANG II-induced renal injury in rats by treating with clopidogrel, a P2Y12 receptor blocker, or with PPADS, a nonselective P2 receptor blocker. α-Actin expression in mesangial cells, afferent arteriolar wall thickness (AAWT), cortical cell proliferation, and macrophage infiltration were used as early markers of renal injury. Clopidogrel and PPADS did not alter blood pressure, renin or kidney ANG II content. α-Actin expression increased from control of 0.6 ± 0.4% of mesangial area to 6.3 ± 1.9% in ANG II-infused rats and this response was prevented by clopidogrel (0.4 ± 0.2%) and PPADS. The increase in AAWT from 4.7 ± 0.1 to 6.0 ± 0.1 mm in ANG II rats was also prevented by clopidogrel (4.8 ± 0.1 mm) and PPADS. ANG II infusion led to interstitial macrophage infiltration (105 ± 16 vs. 62 ± 4 cell/mm2) and tubular proliferation (71 ± 15 vs. 20 ± 4 cell/mm2) and these effects were prevented by clopidogrel (52 ± 4 and 36 ± 3 cell/mm2) and PPADS. RIF ATP levels were higher in ANG II-infused rats than in control rats (11.8 ± 1.9 vs. 5.6 ± 0.6 nmol/l, P < 0.05). The results suggest that activation of vascular and glomerular purinergic P2 receptors may contribute to the mesangial cell transformation, renal inflammation, and vascular hypertrophy observed in ANG II-dependent hypertension.
题名 作者 来源 发表时间

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号