RENALASE: DISCOVERY, BIOLOGY, AND THERAPEUTIC APPLICATIONS.
RENALASE: DISCOVERY, BIOLOGY, AND THERAPEUTIC APPLICATIONS.
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发表时间：
2022
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通讯作者：
G. Desir
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作者：
G. Desir
在研究可能介导慢性肾病（CKD）和终末期肾病（ESRD）患者心血管并发症显著负担的机制时，我们发现了一种以前未知的蛋白质，我们将其命名为肾酶（RNLS）。在过去的15年里，我们对RNLS的生物学、生理学和病理生理学的理解已经成熟。在这里，我们的目的是强调RNLS是一种双功能蛋白质。它代谢细胞内的烟酰胺腺嘌呤二核苷酸（NADH），调节线粒体功能，并保护能量代谢。当分泌到细胞外时，不依赖于其酶特性，它作为信号分子发挥作用，介导对应激刺激的抵抗力并促进细胞和器官存活。RNLS已被证明可以调节胰腺、肝脏、肾脏和心脏急性损伤的严重程度。它还可以防止慢性损伤的发展，在这里，我们强调了外源性RNLS肽激动剂预防顺铂介导的CKD（CP-CKD）的潜在用途。
While investigating the mechanisms that could mediate the significant burden of cardiovascular complications observed in persons with chronic kidney disease (CKD) and end stage renal disease (ESRD), we identified a previously unknown protein, which we named renalase (RNLS). Over the past 15 years, our understanding of the biology, physiology, and pathophysiology of RNLS has matured. Here we aim to highlight that RNLS is a bifunctional protein. It metabolizes intracellular nicotinamide adenine dinucleotide (NADH), modulates mitochondrial function, and protects energy metabolism. When secreted outside the cell, independent of its enzymatic properties, it functions as a signaling molecule that mediates resistance to stressful stimuli and promotes cell and organ survival. RNLS has been shown to modulate the severity of acute injury to the pancreas, liver, kidney, and heart. It also protects against the development of chronic injury, and here we highlight the potential use of exogenous RNLS peptide agonists to prevent cisplatin-mediated CKD (CP-CKD).