Acta physiologica
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Doxorubicin, a potent chemotherapeutic drug, has been demonstrated previously as an inducer of apoptosis in muscle cells. Extensive induction of apoptosis may cause excessive loss of muscle cells and subsequent functional decline in skeletal muscle. This study examined the effects of acylated ghrelin, a potential agent for treating cancer cachexia, on inhibiting apoptotic signalling in doxorubicin-treated skeletal muscle. Unacylated ghrelin, a form of ghrelin that does not bind to GHSR-1a, is also employed in this study to examine the GHSR-1a signalling dependency of the effects of ghrelin. ⋯ Collectively, our data demonstrated that acylated ghrelin administration suppresses the doxorubicin-induced activation of apoptosis and enhances the cellular signalling of autophagy. The treatment of unacylated ghrelin has similar effects as acylated ghrelin on apoptotic and autophagic signalling, suggesting that the effects of ghrelin are probably mediated through a signalling pathway that is independent of GHSR-1a. These findings were consistent with the hypothesis that acylated ghrelin inhibits doxorubicin-induced upregulation of apoptosis in skeletal muscle while treatment of unacylated ghrelin can achieve similar effects as the treatment of acylated ghrelin. The inhibition of apoptosis and enhancement of autophagy induced by acylated and unacylated ghrelin might exert myoprotective effects on doxorubicin-induced toxicity in skeletal muscle.
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It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha-calcitonin-gene-related peptide (αCGRP), known to be released from contracting skeletal muscles, is key at this remodelling. ⋯ Alpha-calcitonin-gene-related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, αCGRP agonists might be beneficial in heart failure patients.
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This study investigated the effects of ageing on the excitability of soleus homonymous Ia afferents and corticospinal pathways during bipedal upright standing. ⋯ This is the first study that clearly indicates lower efficacy of Ia afferents to discharge spinal motor neurones accompanied by greater corticospinal excitability in elderly adults, suggesting an increased contribution of the descending drive in controlling soleus activity during upright standing with ageing.
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To investigate the impact of ischaemic pre-conditioning (Ipre) and post-conditioning (Ipost) on expression of nuclear factor erythroid 2-related factor 2 (Nrf2) gene and its dependent genes, haem oxygenase-1 (HO-1) and NADPH-quinone oxidoreductase-1 (NQO-1); inflammatory cytokines TNF-α, IL1β and ICAM-1; and apoptotic markers such as caspase-3 in renal ischaemia/reperfusion (I/R) injury. ⋯ The renoprotective action of Ipre might include early activation and enhanced expression of Nrf2 gene and its dependent antioxidant genes, HO-1 and NOQ1, as endogenous adaptive renoprotective genes, as well as reduction in TNF-α, IL-1β, ICAM-1 and caspase-3.
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To investigate an interaction between the calcium and sulphide signalling pathways, particularly effects of the slow H2 S release donor morpholin-4-ium-4-methoxyphenyl-(morpholino)-phosphinodithioate (GYY4137) on the expression of inositol 1,4,5-trisphosphate receptors (IP3 R) with the possible impact on the apoptosis induction in HeLa cells. ⋯ These results suggest an involvement of H2 S in both IP3 -induced calcium signalling and induction of apoptosis, possibly through the activation of ER stress.