Prohibitin protects against oxidative stress in intestinal epithelial cells.
Prohibitin (PHB) is an evolutionarily conserved and ubiquitously expressed protein whose expression or function in intestinal diseases is not known. In this study, we examined the expression and role of PHB in oxidative stress associated with inflammatory bowel disease. Our results show that PHB primarily localizes to the mitochondria in intestinal epithelial cells. Its expression is down-regulated during active human Crohn's disease, experimental colitis in vivo, and oxidative stress in vitro. PHB overexpression increases the expression of glutathione-S-transferase pi and protects from oxidant-induced depletion of glutathione. Finally, PHB overexpression decreases accumulation of reactive oxygen metabolites, as well as increased permeability induced by oxidative stress in intestinal epithelial cells. Together, these results suggest that PHB constitutes a previously unrecognized cellular defense against oxidant injury. Thus, strategies to modulate PHB levels may constitute a novel therapeutic approach for intestinal inflammatory diseases, wherein oxidative stress plays a critical role in tissue injury and inflammation.
Theiss
Arianne L
AL
Division of Digestive Diseases, Department of Medicine, Emory University, Atlanta, Georgia 30322, USA. atheiss@emory.edu
Idell
Richard D
RD
Srinivasan
Shanthi
S
Klapproth
Jan-Michael
JM
Jones
Dean P
DP
Merlin
Didier
D
Sitaraman
Shanthi V
SV
D000818:Animals; D018938:Caco-2 Cells; D005978:Glutathione / Q000378:metabolism; D005982:Glutathione Transferase / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015212:Inflammatory Bowel Diseases / Q000378:metabolism*; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018384:Oxidative Stress; D000091402:Prohibitins; D012097:Repressor Proteins / Q000378:metabolism / Q000502:physiology*
C000717328:PHB protein, human; D000091402:Prohibitins; D012097:Repressor Proteins; D016753:Interleukin-10; D006861:Hydrogen Peroxide; D005982:Glutathione Transferase; D005978:Glutathione