In praise of H₂O₂, the versatile ROS, and its vanadium complexes

Abstract

Hydrogen peroxide (H₂O₂) is generated in mitochondria in aerobic cells as a minor product of electron transport, is inhibited selectively by phenolic acids (in animals) or salicylhydroxamate (in plants) and is regulated by hormones and environmental conditions. Failure to detect this activity is due to presence of H₂O₂-consuming reactions or inhibitors present in the reaction mixture. H₂O₂ has a role in metabolic regulation and signal transduction reactions. A number of enzymes and cellular activities are modified, mostly by oxidizing the protein-thiol groups, on adding H₂O₂ in mM concentrations. On complexing with vanadate, also occurring in traces, H₂O₂ forms diperoxovanadate (DPV), stable at physiological pH and resistant to degradation by catalase. DPV was found to substitute for H₂O₂ at concentrations orders of magnitude lower, and in presence of catalase, as a substrate for user reaction, horseradish peroxidase (HRP), and in inactivating glyceraldehyde-3-phosphate dehydrogenase. superoxide dismutase (SOD) -sensitive oxidation of NADH was found to operate as peroxovanadate cycle using traces of DPV and decameric vanadate (V₁₀) and reduces O₂ to peroxide (DPV in presence of free vanadate). This offers a model for respiratory burst. Diperoxovanadate reproduces several actions of H₂O₂ at low concentrations: enhances protein tyrosine phosphorylation, activates phospholipase D, produces smooth muscle contraction, and accelerates stress induced premature senescence (SIPS) and rounding in fibroblasts. Peroxovanadates can be useful tools in the studies on H₂O₂ in cellular activities and regulation.

Keywords::

• Mitochondrial H₂O₂ generation
• alternative oxidase produces H₂O₂
• peroxovanadate substitutes H₂O₂
• H₂O₂ regulates enzymes
• phospholipase D activation
• smooth muscle contraction
• fibroblasts rounding

Acknowledgments

I thank the organizers of the annual meeting of the Society of Free Radicals Research in India held in January 2011 in Chennai, India, particularly, Dr. E. Padmini and Dr. T. P. A. Devasagayam, for giving me an opportunity to present my work and views on H₂O₂. This article closely follows my presentation and is planned to be a brief global perspective of the rapid progress in the field but with an overview of our own contributions with data from our laboratories. My thanks to my colleagues over many years whose work is referred in this article: H. N. Aithal, A. Swaroop, M. S. Patole, P. Kalyani, B. S. Sekhar, R. S. Puranam, Amos Gaikawad, R. V. Omkumar, V. S. Vaidyanathan, H. N. Ravishankar, and V. S. Aparna Rao. Collaborations with many scientists helped our work a great deal: F. L. Crane, Purdue University, West Lafayette, IN, USA; V. Natarajan, Indiana University, Indianapolis, IN, USA; Jeffrey Kanofsky, Layola University, Maywood, IL, USA; Kaleysa Raj, Kerala University, Trivandrum, India; Nashreen Islam, Tezpur University, Tezpur, India; Radha Bhate, Agharkar Research Institute, Pune, India; R. Gayatri, Centre for DNA Fingerprinting & Diagnostics, Hyderabad, India; and Madhu Dikshit, Central Drug Research Institute, Lucknow, India. C. K. R. Kurup of was associated with this work in many ways at Indian Institute of Science, Bangalore, India.

Declaration of interest

The author declares no conflicts of interest. The author alone is responsible for the content and writing of the paper.