TY - JOUR
T1 - Oxidative stress suppresses the cellular bioenergetic effect of the 3-mercaptopyruvate sulfurtransferase/hydrogen sulfide pathway
AU - Módis, Katalin
AU - Asimakopoulou, Antonia
AU - Coletta, Ciro
AU - Papapetropoulos, Andreas
AU - Szabo, Csaba
N1 - Funding Information:
This study was supported by a grant from the Shriners Burns Hospitals and by a grant from the American Diabetes Association ( 7-12-BS-184 ) to C.S. M.K. is supported by the James W. McLaughlin Fellowship Fund of the University of Texas. C.C is supported by a Postdoctoral Fellowship of the American Heart Association. This work has been co-financed by the EU (ESF) and Greek national funds through the Operational Program “Education and Lifelong Learning” of the National Strategic Reference Framework-Research Funding Program: Aristeia 2011 (1436) to A.P.
PY - 2013/4/19
Y1 - 2013/4/19
N2 - Recent data show that lower concentrations of hydrogen sulfide (H2S), as well as endogenous, intramitochondrial production of H2S by the 3-mercaptopyruvate (3-MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron donor and inorganic source of energy to support mitochondrial electron transport and ATP generation in mammalian cells by donating electrons to Complex II. The aim of our study was to investigate the role of oxidative stress on the activity of the 3-MP/3-MST/H2S pathway in vitro. Hydrogen peroxide (H2O2, 100-500μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H2O2 (50-500μM) caused a concentration-dependent decrease in production of H2S from 3-MP. In cultured murine hepatoma cells H2O2, (3-100μM), did not result in overall cytotoxicity, but caused a partial decrease in basal oxygen consumption and respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100-300nM) was completely abolished by pre-treatment of the cells with H2O2 (50μM). The current findings demonstrate that oxidative stress inhibits 3-MST activity and interferes with the positive bioenergetic role of the 3-MP/3-MST/H2S pathway. These findings may have implications for the pathophysiology of various conditions associated with increased oxidative stress, such as various forms of critical illness, cardiovascular diseases, diabetes or physiological aging.
AB - Recent data show that lower concentrations of hydrogen sulfide (H2S), as well as endogenous, intramitochondrial production of H2S by the 3-mercaptopyruvate (3-MP)/3-mercaptopyruvate sulfurtransferase (3-MST) pathway serves as an electron donor and inorganic source of energy to support mitochondrial electron transport and ATP generation in mammalian cells by donating electrons to Complex II. The aim of our study was to investigate the role of oxidative stress on the activity of the 3-MP/3-MST/H2S pathway in vitro. Hydrogen peroxide (H2O2, 100-500μM) caused a concentration-dependent decrease in the activity of recombinant mouse 3-MST enzyme. In mitochondria isolated from murine hepatoma cells, H2O2 (50-500μM) caused a concentration-dependent decrease in production of H2S from 3-MP. In cultured murine hepatoma cells H2O2, (3-100μM), did not result in overall cytotoxicity, but caused a partial decrease in basal oxygen consumption and respiratory reserve rapacity. The positive bioenergetic effect of 3-MP (100-300nM) was completely abolished by pre-treatment of the cells with H2O2 (50μM). The current findings demonstrate that oxidative stress inhibits 3-MST activity and interferes with the positive bioenergetic role of the 3-MP/3-MST/H2S pathway. These findings may have implications for the pathophysiology of various conditions associated with increased oxidative stress, such as various forms of critical illness, cardiovascular diseases, diabetes or physiological aging.
KW - Bioenergetics
KW - Hydrogen sulfide
KW - Mitochondria
KW - Oxidative stress
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U2 - 10.1016/j.bbrc.2013.02.131
DO - 10.1016/j.bbrc.2013.02.131
M3 - Article
C2 - 23537657
AN - SCOPUS:84876470345
SN - 0006-291X
VL - 433
SP - 401
EP - 407
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 4
ER -