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Probing compartment-specific sphingolipids with targeted bacterial sphingomyelinases and ceramidases

机译:用靶向细菌鞘氨基酶和陶瓷酶探测特异性舱鞘脂素

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摘要

Sphingolipids contribute to the regulation of cell and tissue homeostasis, and disorders of sphingolipid metabolism lead to diseases such as inflammation, stroke, diabetes, and cancer. Sphingolipid metabolic pathways involve an array of enzymes that reside in specific subcellular organelles, resulting in the formation of many diverse sphingolipids with distinct molecular species based on the diversity of the ceramide (Cer) structure. In order to probe compartment-specific metabolism of sphingolipids in this study, we analyzed the Cer and SM species preferentially produced in the inner plasma membrane (PM), Golgi apparatus, ER, mitochondria, nucleus, and cytoplasm by using compartmentally targeted bacterial SMases and ceramidases. The results showed that the length of the acyl chain of Cer becomes longer according to the progress of Cer from synthesis in the ER to the Golgi apparatus, then to the PM. These findings suggest that each organelle shows different properties of SM-derived Cers consistent with its emerging distinct functions in vitro and in vivo.
机译:鞘脂素有助于调节细胞和组织稳态,鞘脂代谢的障碍导致炎症,中风,糖尿病和癌症等疾病。鞘脂代谢途径涉及存在于特定亚细胞细胞器中的酶阵列,导致基于神经酰胺(CER)结构的多样性的不同分子物质形成许多不同的鞘脂。为了在本研究中探测鞘脂素的特异性代谢,通过使用间隔靶向细菌侧隙,分析了在内部质膜(PM),高尔基装置,ER,线粒体,细胞核和细胞质中优先产生的CER和SM物种陶瓷酶。结果表明,CER的酰基链条的长度根据ER到GOLGI装置的合成,然后在GOLGI装置中的进展而变长。这些发现表明每个细胞器显示与其在体外和体内的新出现的不同功能一致的SM衍生的CERS的不同性质。

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