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Deletion of caveolin‐1 enhances hepatic heme oxygenase‐1 (HO‐1) induction following endotoxin, especially in female mice.
Author(s) -
Crooks Amanda,
Yavelak Bianca,
Culberson Cathy,
Clemens Mark G
Publication year - 2010
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.24.1_supplement.820.4
Subject(s) - heme oxygenase , lipopolysaccharide , heme , downregulation and upregulation , nitric oxide , endocrinology , medicine , nitric oxide synthase , inflammation , messenger rna , tumor necrosis factor alpha , biology , oxygenase , chemistry , andrology , enzyme , gene , biochemistry
We have previously shown that caveolin‐1 knockout (Cav −/−) mice are protected against endotoxemia and this is associated with preservation of the endothelial nitric oxide synthase activity. However, protection against inflammation can also involve induction of heme oxygenase‐1 (HO‐1). Therefore we tested whether HO‐1 is differentially regulated in Cav −/− mice. Wildtype (WT) and cav −/− mice received i.p. lipopolysaccharide (LPS) or saline and liver tissue samples were taken at either 3 or 6 hours. HO‐1 mRNA levels were significantly induced at 6 but not 3 hours following LPS in male WT mice. In contrast, HO‐1 mRNA was significantly (P< .05) induced at both three and six hours in Cav −/− mice suggesting enhanced HO‐1 induction in Cav −/−. Since previous studies have shown that females are more resistant to LPS than are males, we compared induction of HO‐1 protein in male and female Cav −/− mice at 6 hours after LPS. Both genders showed significant upregulation of HO‐1 protein after LPS but the levels in females were nearly twice that observed in male cav −/− mice. These results suggest that enhanced induction of HO‐1 may contribute to the protective effect of cav‐1 deletion; moreover, the significantly enhanced induction of HO‐1 in females may contribute to their relative tolerance to endotoxemia. Supported by DK 38201‐21