Targeting Calcium and the Mitochondria in Prevention of Pathology in the Heart

Author(s): Helena M. Viola, Livia C. Hool.

Journal Name: Current Drug Targets

Volume 12 , Issue 5 , 2011

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Abstract:

Calcium is a key determinant of cardiac excitation, contraction and relaxation. Cardiac excitation and contraction are powered by ATP that is synthesized within mitochondria via a calcium-dependent process known as oxidative phosphorylation. During this process oxygen molecules within the mitochondria are converted to superoxide. Under physiological conditions, low levels of ROS are required to maintain normal cellular function. This is achieved as a result of a balance between ROS formation and amelioration by antioxidants. Uninhibited increases in ROS production lead to oxidative stress. Large increases in ROS are associated with damage to mitochondria, DNA, proteins and lipids. In the heart this ultimately leads to apoptosis and loss of myocytes. However sub-lethal increases in ROS can activate hypertrophic signaling kinases and transcription factors including NFAT, CaMK and serine-threonine and tyrosine kinases. Calcium is also an important signaling molecule and a mediator of hypertrophic signaling pathways. ROS and calcium appear to participate as partners in pathological remodeling but their interaction and early mechanisms associated with the development of cardiac hypertrophy are poorly understood. An increase in cytoplasmic calcium can potentiate cellular oxidative stress via effects on mitochondrial metabolism. In addition oxidative stress can regulate the function of calcium channels and transporters. We discuss the evidence for calcium transporting proteins and the mitochondria in oxidative stress responses and propose sites to target in the prevention of cardiac hypertrophy.

Keywords: Calcium, mitochondria, reactive oxygen species, cardiac hypertrophy, heart, redox regulation, transporters, pathological growth, antioxidants, TRP channels

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Article Details

VOLUME: 12
ISSUE: 5
Year: 2011
Page: [748 - 760]
Pages: 13
DOI: 10.2174/138945011795378603
Price: $58

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