Ascorbate promotes carbon tetrachloride-induced hepatic injury in senescence marker protein 30-deficient mice by enhancing inflammation
| Autor: | Jin-Kyu Park, Kyu-Shik Jeong, Ah Young Kim, Eun-Mi Lee, Mi-Ran Ki, Hye-Rim Lee, Seung-Sook Lee, Seon-Young Han, Il-Hwa Hong, Sang-Young You |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Premature aging
medicine.medical_specialty Endocrinology Diabetes and Metabolism Clinical Biochemistry Mice Inbred Strains Ascorbic Acid Biology medicine.disease_cause Biochemistry Antioxidants Lipid peroxidation Mice chemistry.chemical_compound Internal medicine medicine Animals Carbon Tetrachloride Molecular Biology Liver injury chemistry.chemical_classification Nutrition and Dietetics Carbon Tetrachloride Poisoning Tumor Necrosis Factor-alpha Glutathione peroxidase Calcium-Binding Proteins Intracellular Signaling Peptides and Proteins JNK Mitogen-Activated Protein Kinases Ascorbic acid medicine.disease Up-Regulation Nitric oxide synthase Oxidative Stress Endocrinology Liver chemistry Toxicity biology.protein Chemical and Drug Induced Liver Injury Inflammation Mediators Oxidative stress |
| Zdroj: | The Journal of Nutritional Biochemistry. 22:535-542 |
| ISSN: | 0955-2863 |
| DOI: | 10.1016/j.jnutbio.2010.04.008 |
| Popis: | 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 SMP30(-/-) mice was less severe than those of wild type (WT) mice, upon chronic CCl(4) injection. The purpose of this study was to investigate the pathophysiology underlying the mild CCl(4) toxicity in SMP30(-/-) mice. Along with the lower level of serum alanine aminotransferase, the livers of SMP30(-/-) 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. CCl(4)-induced proliferation, measured by the expression of proliferating cell nuclear antigen, was low in SMP30(-/-) mice as compared with that of WT mice whereas the levels of p21 and Bax were comparable to those of the CCl(4)-treated WT mice. Moreover, CCl(4) toxicity in ascorbate-fed SMP30(-/-) mice was comparable to that of the CCl(4)-alone treated WT mice, accompanied by an increase in the above mentioned factors. Conversely, ascorbate partly compensated for the CCl(4)-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 SMP30(-/-) mice. |
| Databáze: | OpenAIRE |
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