| 2 | Parkin deficiency accentuates chronic alcohol intake-induced tissue injury and autophagy defects in brain,liver and skeletal muscle显示文摘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 in herited gene for Parkins on's disease and an important member of selective autophagy for mitoch on dria.The associati on between Parkins on's disease and alcoholic injury remains elusive.This study aimed to examine the effect of parki n deficiency on chr onic alcohol in takeinduced 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 toleranee,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 intoleranee,elevated protein carbonyl formation,apoptosis,focal inflammation,necrosis,microvesiculation,autophagy/mitophagy failure and dampened mitochondrial respiration(complexⅣ,complexesⅠandⅢ,and complexesⅡandⅢ)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. | Hu Peng Xing Qin Sainan Chen Asli E Ceylan Maolong Dong Zhaofen Lin Jun Ren | 2020 | Acta Biochimica et Biophysica Sinica2020，52，6： | 3 |
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