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Uncoupling Protein Overexpression in Metabolic Disease and the Risk of Uncontrolled Cell Proliferation and Tumorigenesis

[ Vol. 17 , Issue. 9 ]

Author(s):

A. Ruiz-Ramirez, O. Lopez-Acosta, M. Barrios-Maya and M. El-Hafidi*   Pages 598 - 607 ( 10 )

Abstract:


In metabolic diseases such as obesity, metabolic syndrome and type II diabetes, the over-expression of uncoupling proteins (UCPs) in a response to increased reactive oxygen species (ROS) generation by mitochondrial respiratory complexes, and to the excess of free fatty acid (FFA) supply from adipose tissue, may protect cells from oxidative stress, lipotoxicity and in turn from death. UCPs by reducing superoxide anion and H2O2 generation trigger several signals to cell for their adaptation to the lipotoxic microenvironment. In mitochondria, a decrease of cytochrome c (cyt c) and proapoptotic protein release promotes cell survival and proliferation. The altered lipid metabolism also affects cardiolipin susceptibility to the peroxidation, a process involved in the dissociation of cyt c from mitochondrial inner membrane and its release, a key step of apoptosis. Therefore, UCPs by attenuating ROS generation and lipotoxicity may downregulate programmed cell death, a well-known physiological process controlling cell proliferation contributing to uncontrolled cell proliferation and tumorigenesis. In addition, tumor cells over-expressed UCPs, by inhibiting ROS generation acquire resistance to death during pharmacological treatment with oxidative stress drug inducers. Therefore, the aim of this review is to discuss recent findings regarding the role that UCPs play in cell survival by protecting against ROS generation and maintaining bioenergetic metabolism homeostasis to promote cell proliferation.

Keywords:

Apoptosis, cyt c release, oxidative stress, uncoupling proteins, obesity, cancer.

Affiliation:

Depto. de Biomedicina Cardiovascular, Instituto Nacional de Cardiologia Ignacio Chavez, Juan Badiano No. 1, Colonia Seccion XVI, Tlalpan 14080, Ciudad de Mexico, Depto. de Biomedicina Cardiovascular, Instituto Nacional de Cardiologia Ignacio Chavez, Juan Badiano No. 1, Colonia Seccion XVI, Tlalpan 14080, Ciudad de Mexico, Depto. de Biomedicina Cardiovascular, Instituto Nacional de Cardiologia Ignacio Chavez, Juan Badiano No. 1, Colonia Seccion XVI, Tlalpan 14080, Ciudad de Mexico, Depto. de Biomedicina Cardiovascular, Instituto Nacional de Cardiologia Ignacio Chavez, Juan Badiano No. 1, Colonia Seccion XVI, Tlalpan 14080, Ciudad de Mexico



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