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Published on: May 21, 2020
[Inactivation of Ras1 in Fission Yeast Aggravates the Oxidative Stress Response Induced by Tert Butyl Hydroperoxide
N Masood1, S Anjum2, S Ahmed2,3
1Biochemistry and Structural Biology Division, CSIR-Central Drug Research Institute, Sector 10, Jankipuram Extension, Lucknow, 226031 India.
Abstract:
Ras proteins are small GTPases and function as molecular switches to regulate cellular homeostasis. Ras-dependent signalling pathways regulate several essential processes such as cell cycle progression, growth, migration, apoptosis, and senescence. The dysregulation of Ras signaling pathway has been linked to several pathological outcomes. A potential role of RAS in regulating the redox signalling pathway has been established that includes the manipulation of ROS levels to provide a redox milieu that might be conducive to carcinogenesis. Reactive oxygen species (ROS) and mitochondrial impairment have been proposed as major factors affecting the physiology of cells and implicated in several pathologies. The present study was conducted to evaluate the role of Ras1, tert Butyl hydroperoxide (tBHP), and antimycin A in oxidative stress response in Schizosaccharomyces pombe cells. We observed decreased cell survival, higher levels of ROS, and mitochondrial dysfunctionality in ras1Δ cells and tBHP as well as respiratory inhibitor, antimycin A treated wild type cells. Furthermore, these defects were more profound in ras1Δ cells treated with tBHP or antimycin A. Additionally, Ras1 also has been shown to regulate the expression and activity of several antioxidant enzymes like glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and catalase. Together, these results suggest the potential role of S. pombe Ras1 in mitigating oxidative stress response.
Insights
Schizosaccharomyces pombe Ras1 protein helps cells manage oxidative stress. Ras1 mitigates reactive oxygen species (ROS) and maintains mitochondrial function, protecting against cellular damage.
Area of Science:
- Cell Biology
- Molecular Biology
- Biochemistry
Context:
- Ras proteins are GTPases regulating cellular homeostasis.
- Dysregulated Ras signaling is linked to pathologies.
- Ras proteins influence redox signaling and reactive oxygen species (ROS) levels.
Purpose:
- To investigate the role of Ras1 in oxidative stress response in Schizosaccharomyces pombe.
- To evaluate the effects of tert-Butyl hydroperoxide (tBHP) and antimycin A on Ras1 function.
Summary:
- Ras1 deletion (ras1Δ) and treatment with tBHP or antimycin A decreased cell survival and increased ROS levels and mitochondrial dysfunction.
- These defects were exacerbated in ras1Δ cells under oxidative stress.
- Ras1 regulates antioxidant enzymes including glutathione peroxidase (GSH-Px), glutathione-S-transferase (GST), and catalase.
Impact:
- S. pombe Ras1 plays a significant role in mitigating oxidative stress.
- Findings suggest Ras1's involvement in cellular defense mechanisms against ROS-induced damage.
- This study provides insights into the molecular mechanisms underlying oxidative stress response in yeast.
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