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Reactive oxygen species induce cardiomyocyte apoptosis partly through TNF-alpha
Ryuichi Aikawa1, Yuko Nitta-Komatsubara, Sumiyo Kudoh
1Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan.
Abstract:
Many studies have indicated that oxidative stress induces apoptosis in cardiomyocytes, but its mechanism remains unknown. We examined whether tumor necrosis factor-alpha (TNF-alpha) is involved in oxidative stress-induced cardiomyocyte apoptosis. Pretreatment with anti-TNF-alpha antibody significantly decreased the number of H(2)O(2)-induced TUNEL-positive cardiomyocytes. Expression of TNF-alpha gene was upregulated by H(2)O(2), and H(2)O(2) mildly but significantly increased the concentration of TNF-alpha in the culture medium. Although neither low dose of H(2)O(2) nor TNF-alpha induced apoptosis, stimulation with H(2)O(2) and TNF-alpha synergistically increased apoptosis. These results suggest that oxidative stress induces apoptosis of cardiac myocytes partly through TNF-alpha.
Insights
Oxidative stress triggers cardiomyocyte apoptosis, partly via tumor necrosis factor-alpha (TNF-alpha). Blocking TNF-alpha reduced H(2)O(2)-induced cell death, suggesting its role in this process.
Area of Science:
- Cardiology
- Molecular Biology
- Cell Biology
Background:
- Oxidative stress is known to induce apoptosis in cardiomyocytes.
- The precise molecular mechanisms underlying this process remain largely unelucidated.
Purpose of the Study:
- To investigate the potential role of tumor necrosis factor-alpha (TNF-alpha) in oxidative stress-induced cardiomyocyte apoptosis.
- To determine if TNF-alpha mediates the apoptotic effects of hydrogen peroxide (H(2)O(2)) in cardiac myocytes.
Main Methods:
- Utilized TUNEL assay to quantify apoptosis in cardiomyocytes exposed to H(2)O(2).
- Assessed the effect of anti-TNF-alpha antibody pretreatment on H(2)O(2)-induced apoptosis.
- Measured TNF-alpha gene expression and protein levels in response to H(2)O(2) stimulation.
Main Results:
- H(2)O(2) upregulated TNF-alpha gene expression and increased its concentration in the culture medium.
- Pretreatment with anti-TNF-alpha antibody significantly reduced the number of apoptotic cardiomyocytes induced by H(2)O(2).
- Combined stimulation with H(2)O(2) and TNF-alpha synergistically enhanced cardiomyocyte apoptosis compared to individual treatments.
Conclusions:
- Oxidative stress, specifically H(2)O(2), induces apoptosis in cardiomyocytes partially through the involvement of TNF-alpha.
- TNF-alpha acts as a mediator in the apoptotic pathway initiated by oxidative stress in cardiac myocytes.