Study of HSPB6: Insights into the Properties of the Multifunctional Protective Agent

Abstract

HSPB6(Heat shock protein B6), is also referred to as P20/HSP20. Unlike other many other members of sHSP(small Heat shock protein) family, which tend to form high-molecular-mass oligomers, in solution, human HSPB6 only forms dimers. However, it still exhibits chaperon-like activity comparable with that of HSPB5. It is expressed ubiquitously, with high and constitutive expression in muscular tissues. sHSPs characteristically function as molecular chaperones and HSPB6 also has a molecular chaperone activity. HSPB6 is up-regulated in response to diverse cellular stress or damage and protect cells from otherwise lethal conditions. HSPB6 is widely recognized as a principle mediator of cardioprotective signaling and recent studies have unraveled the protective role of HSPB6 in disease or injury to the central nervous system. Moreover, accumulating evidence has implicated HSPB6 as a key mediator of diverse vital physiological processes, such as smooth muscle relaxation, platelet aggregation. The versatility of HSPB6 can be explained by its direct involvement in regulating different client proteins and its ability to form heterooligomer with other sHSPs, which seems to be dependent on HSPB6 phosphorylation. This review focuses on the properties including expression and regulation pattern, phosphorylation, chaperon activity, multiple cellular targets of HSPB6, as well as its possible role in physical and pathological conditions.

Skeletal muscle DNMT3A plays a necessary role in endurance exercise by regulating oxidative capacity of red muscles

“…Although the benefits of exercise have long been known, its underlying regulatory mechanisms are still not fully understood. Exercise significantly alters the DNA methylation profile of skeletal muscle [29][30][31][32][33][34][35][36][37]. For example, a single bout of aerobic exercise in human subjects transiently induces promoter DNA hypomethylation in important mitochondriarelated transcripts (e.g., PPARGC1A, PDK4, TFAM, and PPARD), followed by an increase in their expression [29].…”

“…Collectively, these data suggest that changes in promoter methylation are associated with alterations in gene expression following aerobic exercise. By the same token, genome-wide studies have reported that both acute and chronic exercise interventions produce profound changes in CpG methylation [29][30][31][32][33][34][35][36][37]. Some of the alterations are concordant with changes in gene expression [29,34,37,40].…”

“…Exercise significantly alters the DNA methylation profile of skeletal muscle [29][30][31][32][33][34][35][36][37]. DNA methylation, a reversible epigenetic mark that usually occurs on a cytosine residue followed by a guanine (CpG), is mediated by a member of the DNA methyltransferase (DNMT) family [38].…”

“…The resultant potassium influx into the matrix lowers the mitochondrial membrane potential, which causes mitochondrial swelling, opening of permeability transition pores, and elevated ROS production [23][24][25]. In addition, NOX-derived ROS causes leakage of Ca2+ from the sarcoplasmic reticulum or entry of extracellular Ca2+, resulting in mitochondrial Ca2+ overload and mitochondrial ROS emission, which ultimately results in muscle fatigue and dysfunction [13,[17][18][19][26][27][28].Exercise significantly alters the DNA methylation profile of skeletal muscle [29][30][31][32][33][34][35][36][37]. DNA methylation, a reversible epigenetic mark that usually occurs on a cytosine residue followed by a guanine (CpG), is mediated by a member of the DNA methyltransferase (DNMT) family [38].…”

“…Methylation prevents the binding of transcriptional machinery that requires interaction with cytosine, usually resulting in transcriptional silencing [39]. Acute and chronic forms of exercise induce both hyper-and hypo-CpG methylation of target loci [29][30][31][32][33][34][35][36][37], and some of these modifications are inversely correlated with gene expression [29,34,37,40]. For example, a single bout of aerobic endurance exercise in human subjects transiently induces promoter hypomethylation in important mitochondria-related transcripts (e.g., PPARGC1A, PDK4, TFAM, and PPARD), followed by an increase in their expression [29].…”