Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1990078 | The Journal of Nutritional Biochemistry | 2011 | 8 Pages |
Abstract
The genetic deletion of the senescence marker protein 30 (SMP30) gene results in ascorbate deficiency and the premature aging processes in mice. Apparent liver injury of SMP30â/â mice was less severe than those of wild type (WT) mice, upon chronic CCl4 injection. The purpose of this study was to investigate the pathophysiology underlying the mild CCl4 toxicity in SMP30â/â mice. Along with the lower level of serum alanine aminotransferase, the livers of SMP30â/â mice revealed a lesser glycogen depletion, a decrease in c-Jun N-terminal kinase (JNK)-mediated inflammatory signaling in parallel with tumor necrosis factor-alpha and interleukin-1 beta, inducible nitric oxide synthase and glutathione peroxidase, and the lower lipid peroxidation as compared to those of WT mice. CCl4-induced proliferation, measured by the expression of proliferating cell nuclear antigen, was low in SMP30â/â mice as compared with that of WT mice whereas the levels of p21 and Bax were comparable to those of the CCl4-treated WT mice. Moreover, CCl4 toxicity in ascorbate-fed SMP30â/â mice was comparable to that of the CCl4-alone treated WT mice, accompanied by an increase in the above mentioned factors. Conversely, ascorbate partly compensated for the CCl4-induced oxidative stress in WT mice, indicating that sufficient ascorbate may be required for an antioxidant function under severe levels of oxidative stress. Our data suggest that the restoration of ascorbate-deficiency reverses a sluggish immune system into an activated condition by an increase in JNK-mediated inflammation and free radical cascade; thus leading to accelerated hepatic damage in SMP30â/â mice.
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Authors
Mi-Ran Ki, Hye-Rim Lee, Jin-Kyu Park, Il-Hwa Hong, Seon-Young Han, Sang-Young You, Eun-Mi Lee, Ah-Young Kim, Seung-Sook Lee, Kyu-Shik Jeong,