Cycloheximide promotes type I collagen maturation mainly via collagen prolyl 4-hydroxylase subunitα2  

作　　者：Run Shi Miao Xu Huazhe Ye Shanshan Gao Jingfeng Li Huan Li Chaoyang Li 

机构地区：[1]Affiliated Cancer Hospital&Institute of Guangzhou Medical University,State Key Laboratory of Respiratory Disease,Guangzhou 510095,China

出　　处：《Acta Biochimica et Biophysica Sinica》2022年第12期1832-1840,共9页生物化学与生物物理学报（英文版）

基　　金：supported by grants from the National Natural Science Foundation of China(Nos.32070147 and 30670170 to C.L.);the Guangzhou Key Medical Discipline Construction Project.

摘　　要：Aberrant deposition of collagen is associated with cancer development and tissue fibrosis.Proline hydroxylation,catalyzed by collagen prolyl 4-hydroxylases(C-P4Hs),is necessary for collagen maturation and secretion.Here,we try to evaluate the mechanism of the regulation of CHX on collagen maturation.Using pepsin digestion,liquid chromatograph mass spectrometry and gene knockout,we find that treatment of mouse embryonic fibroblasts with cycloheximide(CHX)increases type I collagen proline hydroxylation partially via P4HA1 and mainly via P4HA2.Western blot analysis results show that CHX treatment reduces type I collagen but does not obviously impact the level of P4HA1/2 protein in the endoplasmic reticulum,which enhances the molar ratio of P4HA1/2 to type I collagen,and coimmunoprecipitation results confirm that more P4HA1/2 can bind to each type I collagen.Since C-P4Hs possess the capability to hydroxylate proline independent of ascorbate for a few cycles,this enhanced binding between P4HA1/2 and type I collagen can partially explain how CHX stimulates type I collagen maturation.

关 键 词：CYCLOHEXIMIDE type I collagen collagen prolyl 4-hydroxylases proline hydroxylation 

分 类 号：O64[理学—物理化学]