Heme oxygenase isoform-specific expression and distribution in the rat kidney

被引:87
作者
da Silva, JL
Zand, BA
Yang, LM
Sabaawy, HE
Lianos, E
Abraham, NG [1 ]
机构
[1] New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA
[2] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Med, Div Nephrol, New Brunswick, NJ 08903 USA
关键词
blood pressure; hypertension; vasoconstriction; cellular heme; carbon monoxide; kidney function; eicosanoid regulation; HO-1 and HO-2 genes;
D O I
10.1046/j.1523-1755.2001.0590041448.x
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Background. The heme oxygenase (HO) genes, HO-1 and HO-2, are the limiting steps in heme degradation and in the regulation of renal heme-dependent enzymes. Previously we reported that selective overexpression of renal HO-1 resulted in a decrease of microsomal heme and the cytochrome P450-dependent arachidonic acid metabolite, 20 HETE, a vasoconstrictor. The present study was undertaken to explore the relative expression and contribution of each of the HO isoforms to HO activity in the rat kidney. Methods and Results. Renal HO activity increased above control levels after an injection of the inducers of HO activity, heme or SnCl2. Stannous Mesoporphyrin (SnMP), a nonselective inhibitor of HO, when used alone or in combination with heme or SnCl2, decreased HO activity. Heme alone and combined with SnCl2 decreased the levels of heme content by 13 and 35%, respectively. Western blot analysis showed that both SnCl2 and heme readily induced HO-1 protein, whereas HO-2 was constitutively expressed. Immunohistochemistry showed the distribution of the HO-1 isoform primarily in proximaI convoluted tubules. Western blot analysis exhibited relatively higher levels of HO-1 in isolated proximal tubules and relatively higher HO-2 levels in the thick ascending limbs of the loop of Henle and preglomerular arterioles. In vivo administration of HO-1 and HO-2 antisense oligodeoxynucleotides further confirmed that HO-2, but not HO-1, contributed to the basal HO activity; however, following induction of HO with heme, antisense to HO-1, but not to HO-2, inhibited the induced levels of HO activity. Conclusion. These results suggest that HO-2 is constitutively expressed in the rat kidney mainly within tubular and arteriolar structures, and its activity may modulate physiological function under basal conditions. On the other hand, the basal levels of expression of HO-1 in the rat kidney are relatively low, and its contribution to HO activity and the regulation of hemoproteins such as cytochrome P450 become apparent only under pathophysiological conditions causing HO induction.
引用
收藏
页码:1448 / 1457
页数:10
相关论文
共 44 条
  • [1] THE PHYSIOLOGICAL SIGNIFICANCE OF HEME OXYGENASE
    ABRAHAM, NG
    LIN, JHC
    SCHWARTZMAN, ML
    LEVERE, RD
    SHIBAHARA, S
    [J]. INTERNATIONAL JOURNAL OF BIOCHEMISTRY, 1988, 20 (06): : 543 - &
  • [2] EFFECTS OF IRON-DEFICIENCY AND CHRONIC IRON OVERLOADING ON MITOCHONDRIAL HEME BIOSYNTHETIC-ENZYMES IN RAT-LIVER
    ABRAHAM, NG
    CAMADRO, JM
    HOFFSTEIN, ST
    LEVERE, RD
    [J]. BIOCHIMICA ET BIOPHYSICA ACTA, 1986, 870 (02) : 339 - 349
  • [3] The biological significance and physiological role of heme oxygenase
    Abraham, NG
    Drummond, GS
    Lutton, JD
    Kappas, A
    [J]. CELLULAR PHYSIOLOGY AND BIOCHEMISTRY, 1996, 6 (03) : 129 - 168
  • [4] Abraham NG, 2000, J PHARMACOL EXP THER, V293, P494
  • [5] EXPRESSION OF RAT RENAL GAMMA-GLUTAMYL-TRANSPEPTIDASE IN LLC-PK(1) CELLS AS A MODEL FOR APICAL TARGETING
    ALTMAN, RA
    ORR, AV
    LAGENAUR, CF
    CURTHOYS, NP
    HUGHEY, RP
    [J]. BIOCHEMISTRY, 1993, 32 (14) : 3822 - 3828
  • [6] Heme oxygenase-1: Function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury
    Choi, AMK
    Alam, J
    [J]. AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1996, 15 (01) : 9 - 19
  • [7] VASCULAR SMOOTH-MUSCLE CELL HEME OXYGENASES GENERATE GUANYLYL CYCLASE STIMULATORY CARBON-MONOXIDE
    CHRISTODOULIDES, N
    DURANTE, W
    KROLL, MH
    SCHAFER, AI
    [J]. CIRCULATION, 1995, 91 (09) : 2306 - 2309
  • [8] Carbon monoxide formation in the ductus arteriosus in the lamb: Implications for the regulation of muscle tone
    Coceani, F
    Kelsey, L
    Seidlitz, E
    Marks, GS
    McLaughlin, BE
    Vreman, HJ
    Stevenson, DK
    Rabinovitch, M
    Ackerley, C
    [J]. BRITISH JOURNAL OF PHARMACOLOGY, 1997, 120 (04) : 599 - 608
  • [9] TIN-MEDIATED HEME OXYGENASE GENE ACTIVATION AND CYTOCHROME-P450 ARACHIDONATE HYDROXYLASE INHIBITION IN SPONTANEOUSLY HYPERTENSIVE RATS
    DASILVA, JL
    TIEFENTHALER, M
    PARK, E
    ESCALANTE, B
    SCHWARTZMAN, ML
    LEVERE, RD
    ABRAHAM, NG
    [J]. AMERICAN JOURNAL OF THE MEDICAL SCIENCES, 1994, 307 (03) : 173 - 181
  • [10] Nitric oxide induces heme oxygenase-1 gene expression in mesangial cells
    Datta, PK
    Lianos, EA
    [J]. KIDNEY INTERNATIONAL, 1999, 55 (05) : 1734 - 1739