Parkin deficiency accentuates chronic alcohol intake-induced tissue injury and autophagy defects in brain, liver and skeletal muscle

• 作者: Asli F.Ceylan Hu Peng Jun Ren Maolong Dong Sainan Chen Xing Qin Zhaofen Lin
• 来源期刊: 生物化学与生物物理学报（英文版）
• 关键词: parkin chronic alcohol intake tissue damage mitochondria autophagy
• 年，卷（期）: 2020,（6）
• 页码范围: 665-674
• 页数: 10页
• 语种: 英文
• DOI: 10.1093/abbs/gmaa041

摘要

Alcoholism leads to organ injury including mitochondrial defect and apoptosis with evidence favoring a role for autophagy dysregulation in alcoholic damage.Parkin represents an autosomal recessive inherited gene for Parkinson's disease and an important member of selective autophagy for mitochondria.The association between Parkinson's disease and alcoholic injury remains elusive.This study aimed to examine the effect of parkin deficiency on chronic alcohol intake-induced organ injury in brain,liver and skeletal muscle (rectus femoris muscle).Adult parkinknockout (PRK-/-) and wild-type mice were placed on Liber-De Carli alcohol liquid diet (4％) for 12 weeks prior to assessment of liver enzymes,intraperitoneal glucose tolerance,protein carbonyl content,apoptosis,hematoxylin and eosin morphological staining,and mitochondrial respiration (cytochrome c oxidase,NADH:cytochrome c reductase and succinate:cytochrome c reductase).Autophagy protein markers were monitored by western blot analysis.Our data revealed that chronic alcohol intake imposed liver injury as evidenced by elevated aspartate aminotransferase and alanine transaminase,glucose intolerance,elevated protein carbonyl formation,apoptosis,focal inflammation,necrosis,microvesiculation,autophagy/mitophagy failure and dampened mitochondrial respiration (complex Ⅳ,complexes Ⅰ and Ⅲ,and complexes Ⅱ and Ⅲ) in the brain,liver and rectus femoris skeletal muscle.Although parkin ablation itself did not generate any notable effects on liver enzymes,insulin sensitivity,tissue carbonyl damage,apoptosis,tissue morphology,autophagy or mitochondrial respiration,it accentuated alcohol intake-induced tissue damage,apoptosis,morphological change,autophagy/mitophagy failure and mitochondrial injury without affecting insulin sensitivity.These data suggest that parkin plays an integral role in the preservation against alcohol-induced organ injury,apoptosis and mitochondrial damage.