Attenuation of oxidative stress in HL-1 cardiomyocytes improves mitochondrial function and stabilizes Hif-1alpha

Athanassios Vassilopoulos; Panagiota Papazafiri

doi:10.1080/10715760500166685

Attenuation of oxidative stress in HL-1 cardiomyocytes improves mitochondrial function and stabilizes Hif-1alpha

Free Radic Res. 2005 Dec;39(12):1273-84. doi: 10.1080/10715760500166685.

Authors

Athanassios Vassilopoulos¹, Panagiota Papazafiri

Affiliation

¹ Department of Animal and Human Physiology, School of Biology, Faculty of Sciences, University of Athens, Panepistimioupolis, 15784 Athens, Greece.

PMID: 16298857
DOI: 10.1080/10715760500166685

Abstract

HL-1 cardiomyocytes were subjected to simulated hypoxia, in the presence of cobalt chloride, which resulted in reduction of cell viability and induction of DNA laddering, indicating the activation of the apoptotic cascade. In the presence of trolox, ascorbic acid, melatonin and the hybrid compound of trolox and lipoic acid (LaT 3a), cell viability was increased, with LaT 3a exhibiting the best effect. Antioxidant treatment restored ATP levels, abolished laddering of DNA, abrogated MPTP opening, Bax translocation to the mitochondria and cytochrome c release to the cytoplasm. Moreover, severe hypoxia, was found to destabilize hypoxia inducible factor-1alpha (Hif-1alpha) mRNA. Reduction of oxidative stress attenuated this effect, implying a possible anti-apoptotic action of the master regulator of hypoxia response. Our data suggest that antioxidants can maintain cell function and survival by inhibiting the mitochondrial apoptotic pathway and stabilizing Hif-1alpha.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenosine Triphosphate / metabolism
Antioxidants / pharmacology
Apoptosis
Cell Hypoxia
Cell Line
Cobalt / toxicity
Cytochromes c / metabolism
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / genetics
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Ion Channels / metabolism
Mitochondria, Heart / physiology*
Mitochondrial Membrane Transport Proteins
Mitochondrial Permeability Transition Pore
Myocytes, Cardiac / metabolism*
Myocytes, Cardiac / ultrastructure
Oxidative Stress / drug effects*
Protein Transport / drug effects
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism
bcl-2-Associated X Protein / metabolism
bcl-X Protein / metabolism

Substances

Antioxidants
BAX protein, human
BCL2L1 protein, human
HIF1A protein, human
Hypoxia-Inducible Factor 1, alpha Subunit
Ion Channels
Mitochondrial Membrane Transport Proteins
Mitochondrial Permeability Transition Pore
RNA, Messenger
Reactive Oxygen Species
bcl-2-Associated X Protein
bcl-X Protein
Cobalt
Adenosine Triphosphate
Cytochromes c
cobaltous chloride