Sodium pyruvate
"We recently reported that pyruvate inhibited translocation and activation of p53 caused by DNA damage due to oxidant injury (Lee YJ, Kang IJ, Bunger R, and Kang YH. Microvasc Res 66: 91-101, 2003); this was associated with increased expression of apoptosis-related bcl-2 and decreased expression of bax gene."
"Activation of caspase-3 and the cleavage of procaspase-6 and procaspase-7 were strongly inhibited by pyruvate but markedly enhanced by l-lactate and aminooxyacetate, implicating redox-related antiapoptotic mechanisms of pyruvate."
"In addition, H2O2 downregulated extracellular signal-regulated kinase (ERK1/2) and phosphorylated p38 mitogen-activated protein kinase (MAPK), effects that were fully reversed by pyruvate within 2 h."
"Collectively, these findings indicate that pyruvate can protect cellular glutathione, thus enhancing cellular antioxidant potential, and that enhanced antioxidant potential can desensitize NF-kappaB transactivation due to reactive oxygen species, suggesting possible metabolic redox relations to NF-kappaB. Furthermore, pyruvate blocked the p38 MAPK pathway and activated the ERK pathway in an apparently redox-sensitive manner, which may regulate expression of genes believed to prevent apoptosis and promote cell survival. Thus pyruvate may have therapeutic potential for reducing endothelial dysfunction and improving survival during oxidative stress."
“Pyruvat does very much for us. Especially the p38 MAPK pathway inhibtion is of extraordenary value for us. TGF-beta not only activates the SMAD pathway to signal to the nucleus. It also acitvates the TAK1 MAPK pathway and both pathways merge on DNA transcription level in the nucleus and the TAK1 pathway potentiates the actions of the SMADs synergistically (not bare addition), I can proof this with articles and will do so. So inhibition of the TAK1 p38 MAPK pathway will inhibit this synergism and the bare SMAD part will stay. But even if some signals manage to get through ... pyruvate also acts after transcription of the TGF-beta target genes has occured. TGF-beta causes apoptosis by generating ROS (reactive oxigen spezies), I have articles on that. But pyruvate can counteract ROS itself and by preventing glutathione from depletion (very likely it prevents glutathione from depletion because it scavenges the ROS itself (see link above)), thereby protecting the mitochondria from the attack of the ROS and thereby preventing release of cytochrome c and caspase activation and apoptosis.â€
The last one is a comment from Fred.
