Heme oxygenase isoform-specific expression and distribution in the rat kidney
| Autor: | Jean-Louis Da Silva, Li Ming Yang, Nader G. Abraham, Barbara A. Zand, Hatem E. Sabaawy, Elias A. Lianos |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Male
HO-1 and HO-2 genes medicine.medical_specialty hypertension Hemeprotein Cytochrome eicosanoid regulation Heme In Vitro Techniques Kidney carbon monoxide Rats Sprague-Dawley chemistry.chemical_compound Internal medicine cellular heme medicine Loop of Henle vasoconstriction Animals Tissue Distribution kidney function biology blood pressure Tin Compounds Cytochrome P450 Oligonucleotides Antisense Rats Heme oxygenase medicine.anatomical_structure Endocrinology chemistry Nephrology Heme Oxygenase (Decyclizing) biology.protein Microsome Heme Oxygenase-1 |
| Zdroj: | Kidney International. 59:1448-1457 |
| ISSN: | 0085-2538 |
| Popis: | Heme oxygenase isoform-specific expression and distribution in the rat kidney. 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 SnCl 2 . Stannous Mesoporphyrin (SnMP), a nonselective inhibitor of HO, when used alone or in combination with heme or SnCl 2 , decreased HO activity. Heme alone and combined with SnCl 2 decreased the levels of heme content by 13 and 35%, respectively. Western blot analysis showed that both SnCl 2 and heme readily induced HO-1 protein, whereas HO-2 was constitutively expressed. Immunohistochemistry showed the distribution of the HO-1 isoform primarily in proximal 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|