Effects of Tamoxifen on Mitochondrial NOS activity: alteration in the intramitochondrial Ca2+ homeostasis

Author

Sandeep S. Joshi

Date of Award

2005

Degree Name

Biological Sciences

College

College of Science

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Eric Blough

Second Advisor

Pedram Ghafourifar

Third Advisor

Simon Collier

Abstract

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 (∆ψ) 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.

Subject(s)

Tamoxifen.

Mitrochondria.

Recommended Citation

Joshi, Sandeep S., "Effects of Tamoxifen on Mitochondrial NOS activity: alteration in the intramitochondrial Ca2+ homeostasis" (2005). Theses, Dissertations and Capstones. 678.
https://mds.marshall.edu/etd/678