Interaction of glyceraldehyde-3-phosphate dehydrogenase and heme: The relevance of its biological function.
GAPDH was speculated to function as a transient trap to reduce the potential toxicity of free heme by a specific and reversible binding with heme. Up to now, there has been lack of studies focused on this effect. In this paper, the efficiency of GAPDH-heme complex on catalyzing protein carbonylation and nitration, the cross-linking of heme to protein formation, and cytotoxicity of GAPDH-heme were studied. It was found that the binding of GAPDH could inhibit H2O2-mediated degradation of heme. Peroxidase activity of GAPDH-heme complex was higher than that of free heme, but significantly lower than that of HSA-heme. Catalytic activity of heme corresponded complex toward tyrosine oxidation/nitration was decreased in the order of HSA-heme, heme and GAPDH-heme. GAPDH also inhibited heme-H2O2-NO2-induced protein carbonylation. No covalent bond was formed between heme and GAPDH after treated with H2O2. GAPDH was more effective than HSA on protecting cells against heme-NO2--H2O2induced cytotoxicity. These results indicate that binding of GAPDH inhibits the activity of heme in catalyzing tyrosine nitration and protects the coexistent protein against oxidative damage, and the mechanism is different from that of HSA. This study may help clarifying the protective role of GAPDH acting as a chaperone in heme transfer to downstream areas.
School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China.
Yi
Y
Huang
School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China.
Pengfei
P
Zhang
Department of Chemical and Biomolecular Engineering, University of Houston, Houston, TX 77004, United States.
Zhen
Z
Yang
School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China.
Peipei
P
Wang
School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Wuhan, 430074, PR China.
Hailing
H
Li
School of Chemistry and Chemical Engineering, Huazhong University of Science & Technology, Wuhan, 430074, PR China; Hubei Key Laboratory of Bioinorganic Chemistry & Materia Medica, Wuhan, 430074, PR China. Electronic address: zhgao144@hust.edu.cn.
Zhonghong
Z
Gao
D002244:Carbon / Q000737:chemistry; D002384:Catalysis; D045744:Cell Line, Tumor; D002470:Cell Survival; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000737:chemistry*; D006418:Heme / Q000737:chemistry*; D006801:Humans; D006861:Hydrogen Peroxide / Q000737:chemistry; D010084:Oxidation-Reduction; D010100:Oxygen / Q000737:chemistry; D009195:Peroxidase / Q000737:chemistry; D011485:Protein Binding; D050050:Protein Carbonylation; D012709:Serum Albumin / Q000737:chemistry; D014443:Tyrosine / Q000737:chemistry
D012709:Serum Albumin; D014443:Tyrosine; D006418:Heme; D002244:Carbon; D006861:Hydrogen Peroxide; D009195:Peroxidase; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010100:Oxygen
Glyceraldehyde-3-phosphate dehydrogenase; Heme; Peroxidase activity; Protein carbonylation; Tyrosine nitration