1/2/2023 0 Comments Differentiation rc wingIn vitro, GHR inhibits apoptosis of cardiomyocytes and endothelial cells as well as apoptosis of preadipocytic and preosteoblastic cells, through activation of extracellular signal-regulated kinase (ERK)-1/2 and phosphoinositide 3-kinase/Akt pathways ( Baldanzi et al., 2002 Kim et al., 2004 Kim et al., 2005). Moreover, GHR acts as a vasodilator, enhancing nitric oxide bioactivity in metabolic syndrome patients ( Tesauro et al., 2005). In addition to its endocrine activities, GHR features several activities in the cardiovascular system in vivo, as it improves cardiac performances after heart damage ( Nagaya et al., 2001, 2004). GHR exerts these activities through binding and activation of growth hormone secretagogue receptor (GHSR)-1a, a G protein-coupled receptor identified previously as the receptor for synthetic growth hormone secretagogues (GHSs) ( Howard et al., 1996). Ghrelin (GHR) is a circulating peptidyl hormone, octanoylated on Ser3, mainly produced by the stomach, which, by acting on the hypothalamus and the pituitary, induces a strong release of growth hormone (GH) and stimulates food intake and adiposity ( Kojima et al., 1999 Kohno et al., 2003 Reimer et al., 2003). Finally, we show that C2C12 cells do not express GHSR-1a, but they do contain a common high-affinity binding site recognized by both acylated and des-acylated ghrelin, suggesting that the described activities on C2C12 are likely mediated by this novel, yet unidentified receptor for both ghrelin forms. Moreover, the ectopic expression of ghrelin in C2C12 enhances differentiation and fusion of these myoblasts in differentiation medium. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12 proliferation in growth medium. Inhere we show that both ghrelin and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to differentiate and to fuse into multinucleated myotubes in vitro through activation of p38. However, the unacylated ghrelin form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any endocrine activity, is far more abundant than ghrelin in plasma, and it shares with ghrelin some of its cellular activities. Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities. Moreover, ghrelin features several activities such as inhibition of apoptosis, regulation of differentiation, and stimulation or inhibition of proliferation of several cell types. Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and hypothalamus to stimulate appetite, adiposity, and growth hormone release, through activation of growth hormone secretagogue receptor (GHSR)-1a receptor.
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