Enzyme Engineering
Open Access
ISSN: ISSN: 2329-6674
65 3158 1626
ISSN: ISSN: 2329-6674
65 3158 1626
Sandra E Gomez-Mejiba
Laboratory of Experimental Therapeutics, IMIBIO-SL, CONICET,
Suite 13X, Chacabuco 917, San Luis, 5700 San Luis
Argentina
Research Article
Radicalization of Glyceraldehyde-3-Phosphate Dehydrogenase by HOCl in Living Cells
Author(s): Sandra E Gomez-Mejiba, Zili Zhai, Marcos D Muñoz, Cecilia Della Vedova, Kalina Ranguelova, Michael T Ashby and Dario C RamirezSandra E Gomez-Mejiba, Zili Zhai, Marcos D Muñoz, Cecilia Della Vedova, Kalina Ranguelova, Michael T Ashby and Dario C Ramirez
A number of post-translational oxidative modifications of the enzyme ?cell-redox sensor? glyceraldehyde-3- phosphate dehydrogenase (GAPDH) have been reported. These modifications affect GAPDH structure, function, and cell fate; however no free-radical mechanisms have been reported in these processes. Herein we used the nitrone 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-based spin trapping techniques to examine a novel free radical mechanism that causes GAPDH inactivation and aggregation in RAW264.7 cells primed with lipopolysaccharide (LPS). In these primed cells, GAPDH is oxidized by myeloperoxidase (MPO)-derived hypochlorous acid (HOCl) resulting in loss of enzyme activity and aggregation, accumulation of lactate and cell death. Due to the close spatial and physical proximity between MPO and GAPDH, and the oxidizing potential of HOCl, it may be the main species that triggers radicalizatio.. Read More»
DOI:
10.4172/2329-6674.1000134