ABSTRACT
Mitophagy is the process of selective clearance of damaged mitochondria by autophagy. There are several regulatory mechanisms for mitophagy, and the PINK1/Parkin pathway is considered the main pathway for mitophagy. Recent studies have shown that PINK1/Parkin-mediated mitophagy plays an important role in the pathogenesis of various diseases including Parkinson’s disease. This article introduces the mechanism of PINK1/Parkin-mediated mitophagy and its role in various liver diseases including nonalcoholic fatty liver disease, liver fibrosis, and hepatocellular carcinoma, in order to provide new clues and ideas for the treatment of diseases.
ABSTRACT
Hyperhomocysteinemia, which is an independent risk factor for atherosclerosis, may cause aberrant methylation and dysregulation of gene expression, but the characteristics of the aberrant methylation and its key links involved in its pathogenic mechanisms are still poorly understood. The effect of hyperhomocysteine on DNA methylation in vascular smooth muscle cells, its characteristics and the underlying mechanism of Hcy-induced changing in DNA methylation patterns were investigated. Clinical relevant concentrations of homocysteine was added into the cultured vascular smooth muscle cells of the Homo sapien umbilical vein for 24 h. The level of SAM and SAH was detected by HPLC. The activity of SAH Hydrolase was detected by real-time quantitative reverse transcription-PCR and Western blotting analysis. The level and patterns of DNA methylation were measured by endogenous C-5 DNA methyltransferase(C-5 MT-ase) activity and capacity of genomic DNA to accept methyl groups and methylation-dependent restriction analysis. The results indicated that an increased Hcy concentration induced elevated SAH, declined SAM and the ratio of SAM/SAH, reduced expression of SAH Hydrolase, but increased activity of C-5MT-ase. The methylation status of gDNA analyzed by methyl-accepting capacity of gDNA uncovered a demethylation process in gDNA, or homocysteine-caused hypomethylation in gDNA.With different methylation-dependent restriction endonucleases, the aberrant demethylation was found to prefer C↓CGG sequences to CpG islands. The impacts of different dosage of Hcy showed that the varied detrimental effects of Hcy could be attributed to different concentrations via different mechanisms. In mild and moderate hyperhomocysteinemia, the Hcy may primarily influence the epigenetic regulation of gene expression through the interference of transferring methyl-group metabolism, while in more higher Hcy concentration, the notorious impacts may be more directly caused via oxidative stress, apoptosis, inflammation etc.
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Objective To observe the effects of homocysteine on the expression of estrogen receptor alpha(ER?) mRNA and the CpG island methylation of ER? gene promotor region in rats.Methods The serum level of homocysteine in rats was measured by reversed-phase HPLC.RT-PCR and methylated specific PCR(MSP) were applied to assay mRNA expression and the methylation status in promoter CpG island of ER? gene in aorta and cultured rat aortic smooth muscle cells(RASMCs).Results The homocysteine level was increased in ove and ove+H groups(P
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AIM: To observe the effect of platelet-activating factor (PAF) on cultured neuronal viability and glial fibrillary acidic protein (GFAP) expression in cultured astrocytes. METHODS: Neurons and astrocytes obtained from the brain cortex of the embryo and newborn mice respectively were cultured and purified, and they were divided into the control and experimental groups. PAF was added into the experimental groups at concentrations of 4, 8 and 16 ?mol/L. Each group was cultured for 4 h, 24 h and 72 h, respectively. MTT method and immunohistochemistry were used to observe the neuronal viability and GFAP expression in astrocytes, respectively. RESULTS: During different time after adding PAF at different concentrations into cultured neurons and astrocytes, respectively, neuronal viability declined, and the number of astrocytes decreased, but GFAP expression in survival astrocytes increased. The effects were shown to be in a concentration-dependent manner. CONCLUSION: PAF decreases the neuronal viability directly and influences the neuronal survival indirectly by astrocytes.
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AIM: The present study was designed to ex amin e the changes in glial fibrillary acidic protein (GFAP) expression during cerebr al ischemia and the effects of ginkgolide B on GFAP expression. METHODS: The focal thrombotic cerebral ischemia was formed by ph otochemistry-induced in tree shrews. GFAP stained by ABC immunohistochemistry an d absorbance were measured with image analyze system. RESULTS: GFAP expression in astrocytes increased significantly ( P