Klotho: A Study of Oxidative Stress and Homeostasis

Shashank, S (2017) Klotho: A Study of Oxidative Stress and Homeostasis. Masters thesis, Indian Institute of Science Education and Research Kolkata.

PDF (PhD dissertation of Shashank S (12MS020)) 12MS020_MS_THESIS_SHASHANK_S_APRIL_2017.pdf - Submitted Version Restricted to Repository staff only Download (1MB)

Abstract

Klotho is an anti-ageing gene belonging to the glycosidase family-1 of enzymes, which has been shown to reduce the rate of ageing, in mice, rats, zebrafish, and humans. It acts at the organ as well as at the cellular level, to carry out this anti-ageing function. At the cellular level, it has been shown by overexpression studies that klotho is able to strongly activate the Superoxide dismutase (SOD) mediated reactive oxygen species (ROS) scavenging pathway. Yet, whether this is a homeostatic function of klotho, is not known. We investigated this function of klotho by subjecting HEK293 cells to ROS stress using physiologically observed levels of H2O2 and nicotine. Though low levels of H2O2 stress did elicit activation of homeostatic pathways, physiological levels of nicotine caused an overload of ROS which was too high to elicit a homeostatic response, as evinced by the measurement of ROS levels, using H2DCFDA. Further, measurement of klotho levels indicated that H2O2 caused its upregulation at very low levels, while even low levels of nicotine treatment led to a drastic decrease of klotho expression. Thus, we can conclude that very low levels of ROS stress cause an upregulation of klotho expression and elicit a homeostatic response, while higher levels cause a decrease in its expression and are hence, unable to elicit a homeostatic response.

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