Ishemia-Reperfusion enhances GAPDH nitration in aging skeletal muscle

Abstract

Aging and skeletal muscle ischemia/reperfusion (I/R) injury leads to decreased contractile force generation that increases severely with age. Our studies show that glyceraldehyde-3-phosphate dehydrogenase (GAPDH) protein expression is significantly decreased at 3 and 5 days reperfusion in the young mouse muscle and at 1, 3, 5, and 7 days in the aged muscle. Using PCR, we have shown that GAPDH mRNA levels in young and old muscle increase at 5 days reperfusion compared to control, suggesting that the protein deficit is not transcriptional. Furthermore, while total tyrosine nitration did not increase in the young muscle, GAPDH nitration increased significantly at 1 and 3 days reperfusion. In contrast, total tyrosine nitration in aged muscle increased significantly at 1, 3, and 5 days of reperfusion, with increases in GAPDH nitration at the same time points. We conclude that GAPDH protein levels decrease following I/R, that this is not transcriptionally mediated, that the aged muscle experiences greater oxidative stress, protein modification and GAPDH degradation, possibly contributing to decreased muscle function. We propose that tyrosine nitration enhances GAPDH degradation following I/R and that the persistent decrease of GAPDH in aged muscle is due to the prolonged increase in oxidative modification in this age group.

Euphorbia Diterpenes: Isolation, Structure, Biological Activity, and Synthesis (2008–2012)

“…They focused on the anti-MDR and anti-inflammatory activities of the compounds. 105 It was concluded that in case of euphodendroidins a free OH group at C-3, together with the negative effect of this group at C-2 were needed for the anti-MDR activity.…”

“…Finally, in case of pepluane series investigated, pepluanin A with acetyl group at C-8 and nicotinoyl group at C-9 was found to be the most potent inhibitor of Pgp. 105 …”

Skeletal muscle ischemia–reperfusion injury and cyclosporine A in the aging rat

“…Few studies previously examined the effect of hindlimb IR in aged rodents [34,35]. Aged skeletal muscles exhibited more damage and/or defective regeneration following IR [34] and experienced greater oxidative stress, protein modification, and GAPDH degradation, likely contributing to decreased muscle function [35]. Accordingly, the mitochondrial ischemic insult appeared more severe in senescent rats with a more profound decrease in V Max after IR (À70%) as compared to the decreases we previously reported using the same experimental setting in young animals (À36%) [25].…”

Lathyrane diterpenes from Euphorbia lathyris as modulators of multidrug resistance and their crystal structures

“…Recently, considerable attention has been devoted to known compounds jatrophane and lathyrane type which are non-phorboid structures, but have been considered to be potent modulators of MDR. [10][11][12][13][14][15][16][17][18] However, a few types of lathyrane diterpenes were found and only the different substitutions related to anti-MDR bioactivity were focused. 15 The structure-activity relationship has not been elaborated from the aspect of different skeletons.…”