Mechanism of the Regulation of Plasma Cholesterol Levels by PI(4,5)P2.
Mechanism of the Regulation of Plasma Cholesterol Levels by PI(4,5)P2.
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PI(4,5)P2 调节血浆胆固醇水平的机制。
DOI：
10.1007/978-3-031-21547-6_3
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发表时间：
2023
影响因子：
--
通讯作者：
Medina,MarisaW
中科院分区：
文献类型：
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作者：
Qin,Yuanyuan;Medina,MarisaW
低密度脂蛋白（LDL）胆固醇（LDLc）升高是心血管疾病最公认的危险因素之一，而高密度脂蛋白（HDL）胆固醇（HDLc）水平与心血管疾病的保护有关。心血管疾病仍然是全球主要的死亡原因之一;因此，了解影响LDL c和HDL c代谢的机制非常重要。在本章中，我们将讨论磷脂酰肌醇-（4，5）-二磷酸，PI（4，5）P2，被认为是调节LDL c或HDL c的分子过程。第1节将提供循环中胆固醇的概述，讨论调节携带胆固醇的各种形式的脂蛋白（LDL和HDL）的过程。第2节将描述PI（4，5）P2磷酸酶、跨膜蛋白55 B（TMEM 55 B）如何通过其调节低密度脂蛋白受体（LDLR）（肝脏LDL摄取的主要受体）的溶酶体衰变的能力影响循环LDLc水平。第三部分将讨论PI（4，5）P2与HDL中关键载脂蛋白apoA 1的相互作用。除了PI（4，5）P2对循环胆固醇作用的直接机制外，第4节还将回顾PI（4，5）P2如何通过影响胰岛素作用间接影响LDLc和HDLc。最后，由于胆固醇是通过复杂的负反馈回路控制的，第5节将描述PI（4，5）P2是如何受胆固醇调节的。
Elevated low-density lipoprotein (LDL) cholesterol (LDLc) is one of the most well-established risk factors for cardiovascular disease, while high levels of high-density lipoprotein (HDL) cholesterol (HDLc) have been associated with protection from cardiovascular disease. Cardiovascular disease remains one of the leading causes of death worldwide; thus it is important to understand mechanisms that impact LDLc and HDLc metabolism. In this chapter, we will discuss molecular processes by which phosphatidylinositol-(4,5)-bisphosphate, PI(4,5)P2, is thought to modulate LDLc or HDLc. Section 1 will provide an overview of cholesterol in the circulation, discussing processes that modulate the various forms of lipoproteins (LDL and HDL) carrying cholesterol. Section 2 will describe how a PI(4,5)P2phosphatase, transmembrane protein 55B (TMEM55B), impacts circulating LDLc levels through its ability to regulate lysosomal decay of the low-density lipoprotein receptor (LDLR), the primary receptor for hepatic LDL uptake. Section 3 will discuss how PI(4,5)P2interacts with apolipoprotein A-I (apoA1), the key apolipoprotein on HDL. In addition to direct mechanisms of PI(4,5)P2action on circulating cholesterol, Sect. 4 will review how PI(4,5)P2may indirectly impact LDLc and HDLc by affecting insulin action. Last, as cholesterol is controlled through intricate negative feedback loops, Sect. 5 will describe how PI(4,5)P2is regulated by cholesterol.