Sphingomyelinases and Liver Diseases.
Sphingomyelinases and Liver Diseases.
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DOI：
10.3390/biom10111497
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发表时间：
2020-10-30
期刊：
影响因子：
5.5
通讯作者：
Fernandez-Checa JC
中科院分区：
文献类型：
--
作者：
Insausti-Urkia N;Solsona-Vilarrasa E;Garcia-Ruiz C;Fernandez-Checa JC
鞘脂（SL）是膜双层的关键组成部分，在其物理化学性质中起着至关重要的作用。神经酰胺是SL的原型，并且由于其作为第二信使在多种信号传导途径和细胞过程的调节中的作用而被研究得最多。神经酰胺是一种异质脂质实体，由与其碳骨架鞘氨醇连接的脂肪酰基链的长度决定，其可以通过内质网中丝氨酸和棕榈酰辅酶A的从头合成或通过鞘磷脂酶（SM酶）水解鞘磷脂（SM）产生。与从头合成不同，SMase诱导的SM水解代表了神经酰胺在特定细胞内位点产生的快速和瞬时机制，其解释了神经酰胺的多种生物学效应。已经在分子水平上描述了几种SM酶，其表现出不同的活性pH要求：中性、酸性或碱性。在SM酶中，中性（NSM酶）和酸性（ASM酶）是最好的特征，因为它们对信号传导途径的贡献和在包括肝脏疾病在内的多种病理学中的作用。作为特刊（磷脂酶：从结构到生物学功能）的一部分，目前邀请的综述总结了NSMase和ASMase的生理功能及其在慢性和代谢性肝病中的作用，其中最相关的是非酒精性脂肪性肝炎及其进展为肝细胞癌，由于与肥胖和2型糖尿病流行相关。更好地了解SMases在肝脏病理学中的调节和作用可能为肝脏疾病的新治疗提供机会。
Sphingolipids (SLs) are critical components of membrane bilayers that play a crucial role in their physico-chemical properties. Ceramide is the prototype and most studied SL due to its role as a second messenger in the regulation of multiple signaling pathways and cellular processes. Ceramide is a heterogeneous lipid entity determined by the length of the fatty acyl chain linked to its carbon backbone sphingosine, which can be generated either by de novo synthesis from serine and palmitoyl-CoA in the endoplasmic reticulum or via sphingomyelin (SM) hydrolysis by sphingomyelinases (SMases). Unlike de novo synthesis, SMase-induced SM hydrolysis represents a rapid and transient mechanism of ceramide generation in specific intracellular sites that accounts for the diverse biological effects of ceramide. Several SMases have been described at the molecular level, which exhibit different pH requirements for activity: neutral, acid or alkaline. Among the SMases, the neutral (NSMase) and acid (ASMase) are the best characterized for their contribution to signaling pathways and role in diverse pathologies, including liver diseases. As part of a Special Issue (Phospholipases: From Structure to Biological Function), the present invited review summarizes the physiological functions of NSMase and ASMase and their role in chronic and metabolic liver diseases, of which the most relevant is nonalcoholic steatohepatitis and its progression to hepatocellular carcinoma, due to the association with the obesity and type 2 diabetes epidemic. A better understanding of the regulation and role of SMases in liver pathology may offer the opportunity for novel treatments of liver diseases.
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