HO-1 overexpression attenuates endotoxin effects on CAT-2 isozymes expression

l-arginine transport mediated by type-2 cationic amino acid transporter (CAT-2) isozymes is one crucial mechanism that regulates nitric oxide (NO) production via inducible nitric oxide synthase (iNOS). We sought to investigate the effects of heme oxygenase-1 (HO-1) overexpression on CAT-2 isozymes, e.g., CAT-2, CAT-2A, and CAT-2B.

Adult male Sprague Dawley rats were allocated to receive lipopolysaccharide (LPS), normal saline, hemin (a HO-1 inducer), tin protoporphyrin (SnPP, a HO-1 inhibitor), LPS plus hemin, or LPS plus hemin plus SnPP. After maintaining for 6 h, rats were sacrificed and the expression and activity of individual enzyme was evaluated.

LPS increased HO activity, HO-1 concentration, NO production, l-arginine transport, and concentrations of iNOS, CAT-2, and CAT-2B in rat lungs and kidney. LPS also increased HO activity, HO-1 concentration, NO production, l-arginine transport, and iNOS concentration but decreased CAT-2 and CAT-2B concentrations in rat liver. LPS increased CAT-2A concentration in rat liver but did not affect CAT-2A concentration in rat lungs and kidney. Hemin further increased HO activity and induced HO-1 overexpression in the lungs, kidney, and liver from LPS-treated rats. In addition, the effects of LPS on NO production, l-arginine transport, and concentrations of iNOS and CAT-2 isozymes were significantly attenuated by hemin. SnPP, on the other hand, reversed the effects of hemin.

HO-1 overexpression significantly attenuates endotoxin-induced increases in NO production and l-arginine transport. Induction of HO-1 overexpression also significantly attenuates the effects of endotoxin on the expression of iNOS and CAT-2 isozymes in septic rats.