title: [Heat shock response in a rat model of septic multiple organ dysfunction syndrome].
abstract: Severe sepsis is known to result in multiple organ dysfunction syndrome (MODS), which is thought to be mediated by oxidative stress, as a result of excessive systemic inflammation. Heme Oxygenase-1 (HO-1), the rate limiting enzyme in heme catabolism, is also known as HSP32. HO-1 is induced not only by its substrate heme but also by oxidative stress. We investigated gene expression of HO-1 and physiological significance of HO-1 induction in a rat model of septic MODS induced by intraperitoneal injection of bacterial lipopolysaccharide (LPS). Following administration of LPS, HO-1 mRNA was significantly induced in the liver, lung and kidney in an organ-specific manner. Hepatic HO-1 induction appears to be mediated by an increase in hepatic free heme concentration. Inhibition of HO activity by tin mesoporphyrin significantly exacerbated lung injury. These results suggest that HO-1 induction may play an important role in conferring protection on cells from oxidative damage not only by catalyzing heme, a pro-oxidant, but also by producing bilirubin, an anti-oxidant. Furthermore, HO-1 mRNA is induced markedly in the buffy coat of the blood at 3 h after LPS administration, coinciding with the increase in serum IL-6 level, suggesting that HO-1 may be one of the key markers of septic MODS.
authors.affiliation: Department of Anesthesiology and Resuscitology, Okayama University Medical School, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Takahashi
authors.forename: T
authors.initials: T
authors.lastname: Suzuki
authors.forename: A
authors.initials: A
authors.lastname: Yamasaki
authors.forename: T
authors.initials: T
authors.lastname: Tsukiji
authors.forename: M
authors.initials: M
authors.lastname: Hirakawa
authors.forename: R
authors.initials: R
authors.lastname: Akagi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D006360:Heat-Shock Proteins / Q000502:physiology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1; D009102:Multiple Organ Failure / Q000209:etiology / Q000378:metabolism*; D018384:Oxidative Stress; D051381:Rats; D018805:Sepsis / Q000150:complications*
chemical_list: D006360:Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1