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Role of TRPM7 in cerebral ischaemia and hypoxia

机译:TRPM7在脑缺血和缺氧中的作用

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摘要

Transient receptor potential melastatin 7 (TRPM7) channel, a calcium‐permeable non‐selective divalent cation channel, is broadly expressed in various cells and tissues, including the brain. TRPM7 is thought to be coupled to the metabolic state and regulate calcium homeostasis in the cell. TRPM7 takes part in a wide range of cell biology processes that affect cell growth and proliferation, as well as in embryonic development and skeleton formation. TRPM7 plays a significant role in ischaemic and hypoxic brain injury and neuronal cell death. TRPM7, as a key non‐glutamate mechanism of cerebral ischaemia, also triggers an intracellular ionic imbalance and neuronal cell death in ischaemia and hypoxia. We have reported that TRPM7 is expressed in neurons of the hippocampus and cortex and activation of TRPM7 induced ischaemic neuronal cell death; suppression of TRPM7 with virally mediated gene silencing using siRNA reduced ischaemic neuronal cell death and improved neurobehavioural outcomes in vivo. Recently, we also demonstrated that inhibition of TRPM7 using pharmacological means promoted neuronal outgrowth in vitro and provided neuroprotection against brain injury to hypoxia in vivo. Thus, we have shown the contributions of TRPM7 in many physiological and pathophysiological processes, including hypoxia and ischaemia.
机译:瞬态受体电位褪黑素7(TRPM7)通道是钙可渗透的非选择性二价阳离子通道,广泛表达于包括大脑在内的各种细胞和组织中。 TRPM7被认为与代谢状态相关,并调节细胞中的钙稳态。 TRPM7参与了影响细胞生长和增殖以及胚胎发育和骨骼形成的广泛细胞生物学过程。 TRPM7在缺血和缺氧性脑损伤以及神经元细胞死亡中起重要作用。 TRPM7是脑缺血的关键非谷氨酸机制,在缺血和缺氧时也触发细胞内离子失衡和神经元细胞死亡。我们已经报道TRPM7在海马和皮层神经元中表达,并且激活TRPM7诱导缺血性神经元细胞死亡。使用siRNA抑制病毒介导的基因沉默对TRPM7的抑制作用可减少体内缺血性神经元细胞死亡并改善神经行为。最近,我们还证明了使用药理学方法抑制TRPM7可以促进体外神经元的生长,并为体内针对缺氧的脑损伤提供神经保护。因此,我们已经显示了TRPM7在许多生理和病理生理过程中的贡献,包括缺氧和局部缺血。

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