Protein kinase C in heart failure: a therapeutic target?

Abstract

Heart failure (HF) afflicts about 5 million people and causes 300 000 deaths a year in the United States alone. An integral part of the pathogenesis of HF is cardiac remodelling, and the signalling events that regulate it are a subject of intense research. Cardiac remodelling is the sum of responses of the heart to causes of HF, such as ischaemia, myocardial infarction, volume and pressure overload, infection, inflammation, and mechanical injury. These responses, including cardiomyocyte hypertrophy, myocardial fibrosis, and inflammation, involve numerous cellular and structural changes and ultimately result in a progressive decline in cardiac performance. Pharmacological and genetic manipulation of cultured heart cells and animal models of HF and the analysis of cardiac samples from patients with HF are all used to identify the molecular and cellular mechanisms leading to the disease. Protein kinase C (PKC) isozymes, a family of serine–threonine protein kinase enzymes, were found to regulate a number of cardiac responses, including those associated with HF. In this review, we describe the PKC isozymes that play critical roles in specific aspects of cardiac remodelling and dysfunction in HF.

Novel Drp1 inhibitor diminishes aberrant mitochondrial fission and neurotoxicity

“…Our previous studies showed that short peptides derived from interaction sites between two proteins act as highly specific inhibitors and are effective drugs in basic research and in animal models of human diseases, such as myocardial infarction and hypertension (Inagaki et al, 2003;Palaniyandi et al, 2009;Qi et al, 2008). We proposed that because the peptides are flexible and represent part of the natural binding site, they may be superior and more selective inhibitors of PPI as compared with more rigid small molecules (Qvit and Mochly-Rosen, 2010;Ron and Mochly-Rosen, 1995;Souroujon and Mochly-Rosen, 1998).…”

RhoA protects the mouse heart against ischemia/reperfusion injury

“…PKC regulates many cardiac functions, including cardiomyocyte survival (20). To determine the activation status of conventional and novel PKC (nPKC) isozymes, we assessed the membrane and cytosolic localization of 3 representative PKC isozymes.…”

PKC Proteins and Muscular Dystrophy

“…A fundamental role of PKC isoforms has been shown in ischemic preconditioning [52,53]. Moreover, involvement of PKCs in cardiac arrhythmia [54] and heart failure [55] has been recently described. In detail, activation of the epsilon isoform of PKC prevented arrhythmia post ischemic injury [56].…”