Impact of Dysfunctional Protein Catabolism on Macrophage Cholesterol Handling.

Impact of Dysfunctional Protein Catabolism on Macrophage Cholesterol Handling.
Curr Med Chem. 2018 Mar 26;:
Authors: Miyazaki T, Miyazaki A
Abstract
Protein catabolism in macrophages, which is accomplished mainly through autophagy-lysosomal degradation, ubiquitin-proteasome system, and calpains, is disturbed in atheroprone vessels. Moreover, growing evidence suggests that defects in protein catabolism interfere with cholesterol handling in macrophages. Indeed, decreases in autophagy facilitate the deposition of cholesterol in atheroprone macrophages and the subsequent development of vulnerable atherosclerotic plaques due to impaired catabolism of lipid droplets and limited efferocytic clearance of deadly cells. The proteasome is responsible for the degradation of ATP-binding cassette transporters, which leads to impaired cholesterol efflux from macrophages. Overactivation of conventional calpains contributes to the excessive processing of functional proteins, thereby accelerating receptor-mediated uptake of oxidized low-density lipoproteins (LDLs) and slowing cholesterol efflux. Furthermore, calpain-6, an unconventional nonproteolytic calpain in macrophages, potentiates pinocytotic uptake of native LDL and attenuates the efferocytic clearance of deadly cells. Herein, we focus on recent progress in understanding how defective protein catabolism is associated with macrophage cholesterol handling and subsequent atherogenesis.
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Source: Current Medicinal Chemistry - March 26, 2018 Category: Chemistry Authors: Miyazaki T, Miyazaki A Tags: Curr Med Chem Source Type: research