Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leydig and Sertoli cells of the rat testes differ with respect to the activities of the enzymes of the heme and hemoprotein degradative pathway and in their responses to Cd2+ treatment. The microsomal heme oxygenase activity in the Leydig cell preparations was nearly 9- to 10-fold greater than in Sertoli cell preparations, but the characteristics of the enzyme appeared to be similar in both cell populations, as judged by the cofactor requirements and the inhibitory action of heme ligands. Differences between the two cell preparations also were detected in the activity of NADPH-cytochrome c (P-450) reductase and in the contents of cytochrome P-450 and heme, with Leydig cells possessing the higher values. The activities of the cytosolic biliverdin reductase were comparable in both cell preparations. The significantly higher levels of porphyrins and the activities of delta- aminoleuvinate synthetase and uroporphyrinogen-I synthetase suggest that Leydig cells constitute the primary site of heme and hemoprotein biosynthetic activities. The mode of regulation of heme oxygenase activity in the testes and in the liver was compared. The responses of heme oxygenase to Cd2+ treatment (20 mumoles/kg, 24 hr) in the two testicular cell populations were dissimilar and both differed from that of the liver. In Leydig cells, heme oxygenase activity was decreased dramatically, whereas in the liver the activity was greatly increased. Heme oxygenase activity in Sertoli cells was refractory to Cd2+. The Cd2+-mediated decrease in heme oxygenase activity in Leydig cells did not reflect a direct inhibitory action of Cd2+ on the enzyme or a decreased total content of the microsomal protein. The dissimilarity between the mode of regulation of heme metabolic activities in the testes, when determined in Leydig cells, and that in the liver involved the inability of bromobenzene to evoke an increase in heme oxygenase activity and the age-related changes in the activities of heme oxygenase and delta- aminoleuvinate synthetase. In contrast to heme oxygenase activity, the heme concentration in Sertoli cells was remarkably sensitive to Cd2+ treatment, where a 7-fold increase in heme concentration was observed. The same treatment caused only a 2-fold increase in heme concentration in Leydig cells. In the latter cells, however, the increase in heme concentration was accompanied by a marked reduction in cytochrome P-450 levels. The cytochrome could not be measured in Sertoli cell preparations.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Characterization of heme oxygenase activity in Leydig and Sertoli cells of the rat testes. Differential distribution of activity and response to cadmium. 642 20

In the present study, we demonstrate the expression of heme oxygenase (HO) isozymes, HO-1 and HO-2 (listed as HMOX1 and HMOX2 in the MGI Database), in MA-10 Leydig tumor cells and its effect on steroidogenesis. The well-known HO inducer, hemin, increased both HO-1 and HO-2 protein levels and HO-specific activity. Induction of HO by hemin inhibited basal, hCG-, and dibutyryl cAMP (db-cAMP)-induced steroidogenesis in a reversible way. When we studied the effect of HO isozymes along the steroid synthesis, we found that steroidogenic acute regulatory protein levels were decreased, and the conversion of cholesterol to pregnenolone was inhibited by hemin treatment, with no changes in the content of cholesterol side-chain cleavage enzyme (P450scc). hCG and db-cAMP also stimulated the expression of HO-1 and HO-2, and HO enzymatic activity in MA-10 cells. Basal and hCG-stimulated testosterone synthesis was also inhibited by hemin in rat normal Leydig cells. Taken together, these results suggest that: i) at least one of HO products (presumably carbon monoxide) inhibits cholesterol transport to the inner mitochondrial membrane and Leydig cell steroidogenesis by binding to the heme group of the cytochrome P450 enzymes, in a similar way as we described for nitric oxide, and ii) hCG stimulation results in the induction of an antioxidant enzymatic system (HO) acting as a cytoprotective mechanism in Leydig cells, as already demonstrated in the adrenal gland.
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PMID:Effects of heme oxygenase isozymes on Leydig cells steroidogenesis. 1964 13