Premium
Hydrogen sulfide protects against hepatocyte cell death and mitochondrial reactive oxygen during hypoxia
Author(s) -
Norris Eric,
Schleser Franziska,
Culberson Cathy,
Clemens Mark G
Publication year - 2012
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/fasebj.26.1_supplement.1110.5
Subject(s) - hypoxia (environmental) , reactive oxygen species , chemistry , hepatocyte , mitochondrion , liver injury , oxidative stress , oxygen , reperfusion injury , ischemia , medicine , endocrinology , biochemistry , biology , in vitro , organic chemistry
Hydrogen sulfide (H 2 S) is an endogenous gas with important physiological functions. The role of H2S in liver injury remains controversial. Exogenous H 2 S is protective in ischemia/reperfusion and burns, whereas the inhibition of endogenous H 2 S is protective in sepsis models. We have demonstrated increased oxygen consumption in the liver with low levels of exogenous H 2 S (<200ìM) via mitochondrial sulfide oxidation but inhibition at higher levels. In vivo H 2 S infused into the portal vein decreased hepatic tissue PO 2 . Thus, we hypothesized that H 2 S contributes to liver injury via exacerbation of cellular hypoxia. To test this, primary rat hepatocytes were subjected to one hour of hypoxia (PO 2 < 25 mmHg) in the presence of the slow releasing H 2 S donor, GYY 4137 (GYY). Hypoxia caused significant cell death in hepatocytes plated at >75% confluence. Contrary to our hypothesis, GYY significantly improved cell viability following hypoxia (84% survival vs. 30% in control, P= 0.0017). Since mitochondrial stress contributes to cell injury, we tested whether GYY decreased mitochondrial reactive oxygen during hypoxia. GYY significantly reduced mitochondrial ROS in hypoxia as visualized by the mitochondrial ROS specific dye Mitosox (TM) (50.3 vs 31.3 units, P=0.006). Thus, H 2 S protects against hepatocellular injury through a reduction in mitochondrial‐derived reactive oxygen production. Supported by DK38201