Document Details

Document Type:   Thesis
Title:   Effects of Tamoxifen on Mitochondrial NOS Activity: Alteration in the Intramitochondrial Ca2+ Homeostasis
Author:   Sandeep Sudhakar Joshi
College:   Science
Degree Program:   Biological Sciences, M.S.
Degree:   Master of Science
Committee Director:   Dr. Eric Blough
Document Availability:   Document available for World-Wide access.
Date of Defense:   04/25/2005

Tamoxifen (Tam) is an anticancer drug that induces oxidative stress and apoptosis via mitochondria- and nitric oxide (NO)-dependent pathways. Here, we report that therapeutic concentrations of Tam stimulate the mitochondrial NO synthase (mtNOS) activity of isolated rat liver mitochondria by increasing the intramitochondrial ionized Ca2+ concentration ([Ca2+]m). Tam decreases transmembrane potential () due to increased [Ca2+]m that neutralizes the negative charges of the inner mitochondrial membrane. Thus, the present study reports a novel mechanism for the widely used anti-caner drug, Tam. 

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