Journal of Surgical Research
Volume 148, Issue 2 , Pages 172-180, August 2008

HO-1 Overexpression Attenuates Endotoxin Effects on CAT-2 Isozymes Expression1

  • Te-Yang Huang, M.D.

      Affiliations

    • Department of Orthopedics, Mackay Memorial Hospital, Taipei, Taiwan
    • Department of Hyperbaric Oxygen Center, Mackay Memorial Hospital, Taipei, Taiwan
    • ,
  • Pei-Shan Tsai, Ph.D.

      Affiliations

    • College of Nursing, Taipei Medical University, Taipei, Taiwan
    • ,
  • Chun-Jen Huang, M.D., Ph.D.

      Affiliations

    • Department of Anesthesiology, Mackay Memorial Hospital, Taipei, Taiwan
    • Mackay Medicine, Nursing, and Management College, Taipei, Taiwan
    • Graduate Institute of Pharmacology, Taipei Medical University, Taipei, Taiwan
    • Corresponding Author InformationTo whom correspondence and reprint requests should be addressed at Department of Anesthesiology, Mackay Memorial Hospital, 92, Sec. 2 Chung San N. Rd., Taipei 10449, Taiwan.

Received 11 May 2007 published online 03 August 2007.

Background

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.

Materials and Methods

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.

Results

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.

Conclusions

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.

Key Words: heme oxygenase-1, inducible nitric oxide synthase, nitric oxide, l-arginine, type-2 cationic amino acid transporter

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1 Te-Yang Huang and Pei-Shan Tsai contributed equally to this work.

PII: S0022-4804(07)00446-5

doi:10.1016/j.jss.2007.06.027

Journal of Surgical Research
Volume 148, Issue 2 , Pages 172-180, August 2008

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