Satellite cell activation in stretched skeletal muscle and the role of nitric oxide and hepatocyte growth factor

Abstract

In the present study, we examined the roles of hepatocyte growth factor (HGF) and nitric oxide (NO) in the activation of satellite cells in passively stretched rat skeletal muscle. A hindlimb suspension model was developed in which the vastus, adductor, and gracilis muscles were subjected to stretch for 1 h. Satellite cells were activated by stretch determined on the basis of 5-bromo-2'-deoxyuridine (BrdU) incorporation in vivo. Extracts from stretched muscles stimulated BrdU incorporation in freshly isolated control rat satellite cells in a concentration-dependent manner. Extracts from stretched muscles contained the active form of HGF, and the satellite cell-activating activity could be neutralized by incubation with anti-HGF antibody. The involvement of NO was investigated by administering nitro-L-arginine methyl ester (L-NAME) or the inactive enantiomer N(G)-nitro-D-arginine methyl ester HCl (D-NAME) before stretch treatment. In vivo activation of satellite cells in stretched muscle was not inhibited by D-NAME but was inhibited by L-NAME. The activity of stretched muscle extract was abolished by L-NAME treatment but could be restored by the addition of HGF, indicating that the extract was not inhibitory. Finally, NO synthase activity in stretched and unstretched muscles was assayed in muscle extracts immediately after 2-h stretch treatment and was found to be elevated in stretched muscle but not in stretched muscle from L-NAME-treated rats. The results of these experiments demonstrate that stretching muscle liberates HGF in a NO-dependent manner, which can activate satellite cells.

Facioscapulohumeral muscular dystrophy region gene 1 over-expression causes primary defects of myogenic stem cells

“…Interestingly, nitric oxide synthase 1 (Nos1) was found to be downregulated in FRG1 muscles. Nos1 activity inhibition by pharmacological treatment or a knockout approach reduces the activation of satellite cells and leads to muscle regeneration deficit (Anderson, 2000;Tatsumi et al, 2002;Tatsumi et al, 2006). Therefore, it is tempting to speculate that the FRG1 satellite cell defects could be associated with this pathway.…”

Satellite cell activation and populations on single muscle-fiber cultures from adult zebrafish (Danio rerio)

“…Two chemical mediators, nitric oxide (NO) and hepatocyte growth factor (HGF), and mechanical stretch (a culture model of exercise) activate SCs in mammals, as shown in cultures of dispersed SCs (Tatsumi et al, 2001;Tatsumi et al, 2002;Tatsumi et al, 2006;Tatsumi and Allen, 2008) and isolated fibers (Wozniak et al, 2003;Anderson and Wozniak, 2004;Wozniak and Anderson, 2007;Anderson et al, 2012;Anderson and Pilipowicz, 2002;Bischoff, 1975;Bischoff, 1986;Bischoff, 1990) and in vivo (Anderson, 2000;Anderson and Wozniak, 2004;Tatsumi and Allen, 2008). Calcium-dependent stretch-activated signals release NO from mechano-sensitive NOS-1μ, which induces HGF release from the extracellular matrix (Tatsumi et al, 2002;Yamada et al, 2006;Tatsumi et al, 2009;Hara et al, 2012).…”

Suplementação proteica não aumenta a concentração plasmática de óxido nítrico em homens saudáveis

“…Ambas as isoformas apresentaram aumento de expressão da NOS após o modelo de sobrecarga mecânica (18) . O NO também é um potente estimulador das células-satélite (19,20) . Consequentemente, além da hipótese da supercirculação, outro provável efeito da estimulação da síntese de NO sobre o processo de hipertrofia poderia ser modulado pela ativação das células-satélite.…”