Protein kinase C and cardiac dysfunction: a review

Abstract

Heart failure (HF) is a physiological state in which cardiac output is insufficient to meet the needs of the body. It is a clinical syndrome characterized by impaired ability of the left ventricle to either fill or eject blood efficiently. HF is a disease of multiple aetiologies leading to progressive cardiac dysfunction and it is the leading cause of deaths in both developed and developing countries. HF is responsible for about 73,000 deaths in the UK each year. In the USA, HF affects 5.8 million people and 550,000 new cases are diagnosed annually. Cardiac remodelling (CD), which plays an important role in pathogenesis of HF, is viewed as stress response to an index event such as myocardial ischaemia or imposition of mechanical load leading to a series of structural and functional changes in the viable myocardium. Protein kinase C (PKC) isozymes are a family of serine/threonine kinases. PKC is a central enzyme in the regulation of growth, hypertrophy, and mediators of signal transduction pathways. In response to circulating hormones, activation of PKC triggers a multitude of intracellular events influencing multiple physiological processes in the heart, including heart rate, contraction, and relaxation. Recent research implicates PKC activation in the pathophysiology of a number of cardiovascular disease states. Few reports are available that examine PKC in normal and diseased human hearts. This review describes the structure, functions, and distribution of PKCs in the healthy and diseased heart with emphasis on the human heart and, also importantly, their regulation in heart failure.

Long-Term Oral Administration of Theaphenon-E Improves Cardiomyocyte Mechanics and Calcium Dynamics by Affecting Phospholamban Phosphorylation and ATP Production

“…It is well known that the cardiac excitation-contraction coupling is highly dependent on Ca 2+ transient, that is handled through an array of ion channels, antiporters and pumps that are finally regulated, at post-translational level, by phosphorylation. Many kinases have been implicated in the regulation of Ca 2+ transient, such as PKA, CamKII and PKC [47][48][49]. New findings highlight the role, overlooked for many years, of phosphatases in the fine tuning of the phosphorylation balance of physiologically relevant targets [45,50,51].…”

De novo variants in exomes of congenital heart disease patients identify risk genes and pathways

“…Interestingly, five of the 23 candidate genes (ROCK2, BRD4, TJP2, MINK1, and CDK13) were kinases (Table 2), a class of proteins that has previously been implicated in cardiac diseases [79][80][81][82][83]. Two of the DNVs, p.D255G in ROCK2 and p.N842S in CDK13, were predicted to alter the protein kinase domains by subRVIS [40] (Additional file 8: Table S39).…”

Diabetes Mellitus and Pulmonary Circulation (Part 1)

“…За гіперглікемії значно зростає синтез діацилгліцеролу, який є активатором класичних ізоформ ферменту протеїнкінази С (-β, -δ, -α) [47]. Загалом протеїнкіназа С має 12 ізоформ [48,49], деякі з них надмірно активуються чи експресується у ГМК судин та ендотеліоцитах за ЦД, а саме ізоформи -a, -b1, -b2, -g, -e, -z та -d [50,51]. Основним механізмом, що запускає активацію протеїнкінази С при цьому захворюванні, вважають збільшення кількості АФК, а підвищення активності цієї кінази додатково посилює окисний стрес [19].…”