Redox regulation kinase activity

Moreover GSH concentration indirectly controls a host of redox-sensitive transcription factors such as NF-kB and AP-1, modulates the genes for pro-inflammatory mediators as well as protective antioxidant genes such as y-GCS, Mn-superoxide dismutase, and heme oxygenase-1. Also TNF-a, p38 MAP kinase activation and p38 MAP kinase-mediated RANTES (regulated upon activation, normal T-cells expressed and secreted ) production is redox regulated [24]. The role of RANTES in the inflammatory and allergic response has been recently elucidated [25], indicating a role of intracellular GSH also in this particular field of inflammation. 

It does not seem feasible to us that modulation of kinase activity by regulation of proton flow in membrane-associated electric fields can be the sole determinant of the directionality and flux of metabolic pathways. If, as suggested by others, " dehydrogenase-catalyzed reactions were to be poised close to chemical equilibrium, the inevitable consequence would be a pooling of the components of these reactions and proticity would be ineffective as a driving force over the total pathway. It seems reasonable to assume, therefore, that cellular redox reactions are also driven.The electrochemical interpretation of metabolism presented here provides a straightforward mechanism for explaining how this could come about. 

The molecular mechanism by which curcumin can inhibit these transcription frictors is complex. Since they are redox-regulated, curcumin may suppress tiieir activation by removing free radicals. At another level, curciunin may block activaticm by blocking signal transducticm. Curcumin inhibits activation of protein kinase C and phosphotylase kinase (23, 26). It also inhibits inhibitor kappa B (IkB) kinases 1 and 2 (IKKl and 2), blocks phosphoiylaticm of IkB, and suppresses IkB dissociaticm from the p6S submit of NFkB (23, 27). 

Kim JH, Na HJ, Kim CK, Kim JY, Ha KS, Lee H, Chung HT, Kwon HJ, Kwon YG and Kim YM. 2008. The non-provitamin A carotenoid, lutein, inhibits NF-KB-dependent gene expression through redox-based regulation of the phosphatidylinositol 3-kinase/PTEN/Akt and NF-KB-inducing kinase pathways role of H2O2 in NF-kB activation. Free Radic Biol Med 45(6) 885-896. 

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