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Nuclear complex of glyceraldehyde‐3‐phosphate dehydrogenase and DNA repair enzyme apurinic/apyrimidinic endonuclease I protect smooth muscle cells against oxidant‐induced cell death
Author(s) -
Hou Xuwei,
Snarski Patricia,
Higashi Yusuke,
Yoshida Tadashi,
Jurkevich Alexander,
Delafontaine Patrick,
Sukhanov Sergiy
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201601082r
Subject(s) - ap site , endonuclease , chemistry , glyceraldehyde 3 phosphate dehydrogenase , dehydrogenase , dna repair , dna , enzyme , proliferating cell nuclear antigen , dna (apurinic or apyrimidinic site) lyase , biochemistry , base excision repair , microbiology and biotechnology , biology
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 H 2 O 2 ‐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 upregulated Ape1 via 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. FASEB J. 31, 3179–3192 (2017). www.fasebj.org