Differential suitability of reactive oxygen species and the role of glutathione in regulating paradoxical behavior in gliomas: A mathematical perspective

PLoS One. 2020 Jun 25;15(6):e0235204. doi: 10.1371/journal.pone.0235204. eCollection 2020.

Abstract

Manipulative strategies of ROS in cancer are often exhibited as changes in the redox and thiol ratio of the cells. Cellular responses to oxidative insults are generated in response to these changes which are triggered due to the rerouting of the metabolic framework to maintain survival under stress. However, mechanisms of these metabolic re-routing are not clearly understood and remained debatable. In the present work, we have designed a context-based dynamic metabolic model to establish that the coordinated functioning of glutathione peroxidase (GTHP), glutathione oxidoreductase (GTHO) and NADPH oxidase (NOX) is crucial in determining cancerous transformation, specifically in gliomas. Further, we propose that the puzzling duality of ROS (represented by changes in h2o2 in the present model) in exhibiting varying cellular fates can be determined by considering simultaneous changes in nadph/nadp+ and gsh/gssg that occur during the reprogramming of metabolic reactions. This will be helpful in determining the pro-apoptotic or anti-apoptotic fate of gliomas and can be useful in designing effective pro-oxidant and/or anti-oxidant therapeutic approaches against gliomas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • Glioma / metabolism*
  • Glioma / pathology
  • Glutathione / metabolism*
  • Humans
  • Models, Biological*
  • Neoplasm Proteins / metabolism
  • Oxidoreductases / metabolism
  • Reactive Oxygen Species / metabolism*

Substances

  • Neoplasm Proteins
  • Reactive Oxygen Species
  • Oxidoreductases
  • Glutathione

Grants and funding

We thank SERB, Department of Science and Technology, Govt. of India (File No. EMR/2016/000516) and (DST/ICPS/EDA/2018), for providing financial support to Ram Rup Sarkar. Rupa Bhowmick acknowledges the Council of Scientific & Industrial Research (CSIR) for the Senior Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.