Nuclear complex of glyceraldehyde‐3‐phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant‐induced cell death

Abstract

Atherosclerotic plaque destabilization is the major determinant of most acute coronary events. Smooth muscle cell (SMC) death contributes to plaque destabilization. Here, we describe a novel antiapoptotic mechanism in vascular SMCs that involves interaction of nuclear glyceraldehyde-3-phosphate dehydrogenase (GAPDH) with apurinic/apyrimidinic endonuclease 1 (Ape1), the major oxidized DNA repair enzyme. GAPDH down-regulation potentiated HO-induced DNA damage and SMC apoptosis. Conversely, GAPDH overexpression decreased DNA damage and protected SMCs against apoptosis. Ape1 down-regulation reversed the resistance of GAPDH-overexpressing cells to DNA damage and apoptosis, which indicated that Ape1 is indispensable for GAPDH-dependent protective effects. GAPDH bound Ape1 in the SMC nucleus, and blocking (or oxidation) of GAPDH active site cysteines suppressed GAPDH/Ape1 interaction and potentiated apoptosis. GAPDH up-regulated Ape1 a transcription factor homeobox protein Hox-A5-dependent mechanism. GAPDH levels were reduced in atherosclerotic plaque SMCs, and this effect correlated with oxidative stress and SMC apoptosis. Thus, we demonstrated that nuclear GAPDH/Ape1 interaction preserved Ape1 activity, reduced DNA damage, and prevented SMC apoptosis. Suppression of SMC apoptosis by maintenance of nuclear GAPDH/Ape1 interactions may be a novel therapy to increase atherosclerotic plaque stability.-Hou, X., Snarski, P., Higashi, Y., Yoshida, T., Jurkevich, A., Delafontaine, P., Sukhanov, S. Nuclear complex of glyceraldehyde-3-phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant-induced cell death.

Anti‐human serum albumin autoantibody may be involved in the pathogenesis of autoimmune bullous skin diseases

“…Inconsistent results have been reported on the possible enhancement of DNA damage by GAPDH downregulation 44‐46 . The present study showed that GAPDH protein was downregulated in HSA pAb‐treated human skin, and GAPDH gene expression was downregulated in HSA pAb‐treated human skin and HaCaT.…”

Absolute expressions of hypoxia-inducible factor-1 alpha (HIF1A) transcript and the associated genes in chicken skeletal muscle with white striping and wooden breast myopathies

“…Decreased GAPDH protein level has been shown to induce cell cycle arrest and hinder cell proliferation in carcinoma cell lines, suggesting a regulatory role [67]. The protective effect of GAPDH against oxidative-stress-induced apoptosis has been demonstrated in vascular smooth muscle cells [68]. Taken together, down-regulation of GAPDH within the WS and WB samples may link to other cellular roles of GAPDH in response to the hypoxic condition within the muscle.…”

HOXA5 Is Recognized as a Prognostic-Related Biomarker and Promotes Glioma Progression Through Affecting Cell Cycle

“…The product of HOXA5 is a DNA-binding transcription factor and able to regulate multiple gene expression, including TP53. Previous study reported that HOXA5 can bind to the promoter of TP53 to activate its transcription and affect corresponded pathways (16,37). HOXA5 affected tumor progression through influencing TP53 homeostasis in breast cancer (10,38), TP53-dependent apoptosis in liposarcomas (39), and TP53-mediated cell proliferation in cervical cancer (16).…”