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Inactivation of Ras1 in Fission Yeast Aggravates the Oxidative Stress Response Induced by Tert Butyl Hydroperoxide (tBHP)

  • MOLECULAR BIOLOGY OF THE CELL
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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.

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ACKNOWLEDGMENTS

This work was supported by grants from the Science and Engineering Research Board (SERB), India (PDF/2016/001797) and Council of Scientific and Industrial Research New Delhi, India. Simmi Anjum acknowledges University Grant Commission (UGC), India for providing the research fellowship. The CDRI manuscript number for this manuscript is 10521.

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Authors and Affiliations

  1. Biochemistry and Structural Biology Division, CSIR—Central Drug Research Institute, Sector 10, Jankipuram Extension, 226031, Lucknow, India

    N. Masood

  2. Academy of Scientific and Innovative Research (AcSIR), 201002, Ghaziabad, India

    S. Anjum & S. Ahmed

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  1. N. Masood
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  2. S. Anjum
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N. Masood conceived the study protocol; N. Masood and S. Anjum performed the experiment; S. Anjum assisted to prepare the manuscript; S. Ahmed supervised the study and wrote the manuscript.

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Correspondence to S. Ahmed.

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The authors declare that they have no conflicts of interest with the contents of this article. This article does not contain any studies with animal or human participants performed by any of the authors.

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Masood, N., Anjum, S. & Ahmed, S. Inactivation of Ras1 in Fission Yeast Aggravates the Oxidative Stress Response Induced by Tert Butyl Hydroperoxide (tBHP). Mol Biol 57, 692–699 (2023). https://doi.org/10.1134/S002689332304012X

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