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Hydrogen peroxide-dependent declines in Bcl-2 induces apoptosis in hypoxic liver1 <FN ID="FN1"><NO>1</NO>This work was supported in part by Grant-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan.</FN>
- Source :
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Journal of Surgical Research . Mar2003, Vol. 110 Issue 1, p211. 6p. - Publication Year :
- 2003
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Abstract
- Background. Low-flow hypoxia induces xanthine oxidase-dependent hydrogen peroxide production by hepatocytes in the midzone of blood-perfused rat livers and apoptosis in sinusoidal endothelial cells (SECs). As Bcl-2 is a potent inhibitor of apoptotic cell death and is localized mainly in the inner mitochondrial membrane and crista, the purpose of this study was to determine whether cell-specific changes in mitochondrial Bcl-2 levels could account for the hypoxia-induced apoptosis in SECs.Materials and methods. A low-flow hypoxia model was generated in isolated rat livers by reducing perfusate inflow pressure from 10 to 2.5 cmH2O for 2 h. Apoptosis was then evaluated using the TdT-mediated dUTP-digoxigenin nick end-labeling (TUNEL) method. Mitochondrial Bcl-2 protein levels were determined in hepatocytes and SECs using cryosectioning immunogold labeling electron microscopy.Results. TUNEL-positive nonparenchymal cells, identified as SECs, were observed predominantly in the midzone of low-flow hypoxic rat livers, whereas few parenchymal cells were stained. Mitochondrial Bcl-2 levels were higher in SECs than in hepatocytes under control conditions, but they declined significantly during hypoxia, though no morphological signs of apoptosis were apparent. In hepatocytes, by contrast, Bcl-2 levels were unaffected by hypoxia. Pretreatment with a specific xanthine oxidase inhibitor, sodium (-)-8-(3-methoxy-4-phenylsulfinylphenyl) pyrazolo [1,5-a]-1,3,5-triazine-4-olate monohydrate, which blocks production of hydrogen peroxide, also blocked both the hypoxia-induced apoptosis and the decline in mitochondrial Bcl-2 in SECs.Conclusion. Hydrogen peroxide-dependent declines in Bcl-2 induce apoptosis in SECs in the hypoxic rat liver. [Copyright &y& Elsevier]
- Subjects :
- *LIVER
*HYPOXEMIA
*HYDROGEN peroxide
Subjects
Details
- Language :
- English
- ISSN :
- 00224804
- Volume :
- 110
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Surgical Research
- Publication Type :
- Academic Journal
- Accession number :
- 9496287
- Full Text :
- https://doi.org/10.1016/S0022-4804(03)00006-4