Caspase 2 activation and ER stress drive rapid Jurkat cell apoptosis by clofibrate.

Differently from the antiapoptotic action most commonly assigned to peroxisome proliferators (PPs), we demonstrated that some of them, clofibrate (CF) in particular, display clearcut apoptogenic properties on rat hepatoma cell lines. We and others could confirm that CF as well as various other PPs can induce apoptosis in a variety of cells, including human liver, breast and lung cancer cell lines. The present study was aimed at investigating the cytotoxic action of CF on a neoplastic line of different origin, the human T leukemia Jurkat cells.

Glutamine prevents myostatin hyperexpression and protein hypercatabolism induced in C2C12 myotubes by tumor necrosis factor-α.

Depletion of skeletal muscle protein mainly results from enhanced protein breakdown, caused by activation of proteolytic systems such as the Ca2+-dependent and the ATP-ubiquitin-dependent ones. In the last few years, enhanced expression and bioactivity of myostatin have been reported in several pathologies characterized by marked skeletal muscle depletion. More recently, high myostatin levels have been associated with glucocorticoid-induced hypercatabolism.

Deacetylase inhibitors modulate the myostatin/follistatin axis without improving cachexia in tumor-bearing mice.

Muscle wasting, as occurring in cancer cachexia, is primarily characterized by protein hypercatabolism and increased expression of ubiquitin ligases, such as atrogin-1/MAFbx and MuRF-1. Myostatin, a member of the TGFbeta superfamily, negatively regulates skeletal muscle mass and we showed that increased myostatin signaling occurs in experimental cancer cachexia. On the other hand, enhanced expression of follistatin, an antagonist of myostatin, by inhibitors of histone deacetylases, such as valproic acid or trichostatin-A, has been shown to increase myogenesis and myofiber size in mdx mice.

Mechanisms of clofibrate-induced apoptosis in Yoshida AH-130 hepatoma cells.

Peroxisome proliferators (PPs) are a class of compounds that exert their nominal effects through the peroxisome proliferator-activated receptors. PPs, among which clofibrate (CF), have been extensively studied for their hepatocarcinogenic properties in rodents, generally ascribed to their antiapoptotic action. However, previous results demonstrated that various PPs may also have apoptogenic properties.

Muscle myostatin signalling is enhanced in experimental cancer cachexia.

Background/aims: Myostatin belongs to the transforming growth factor-beta superfamily and negatively regulates skeletal muscle mass. Its deletion induces muscle overgrowth, while, on the contrary, its overexpression or systemic administration cause muscle atrophy. The present study was aimed at investigating whether muscle depletion as occurring in an experimental model of cancer cachexia, the rat bearing the Yoshida AH-130 hepatoma, is associated with modulations of myostatin signalling and whether the cytokine tumour necrosis factor-alpha may be relevant in this regard.