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

There is a wide range of change in both microsomal heme oxygenase activity and cytochrome P-450 level in the livers of rats of various ages. We tried to investigate the phases of heme oxygenase activity, both spontaneous and caused by typical MFO inducers in the lifetime of the rat. Wistar male rats aged 0.5, 1, 2, 4, 8, 12, 20 and 28 months received phenobarbital (50 mg/kg) twice, 3 and 2 days before being killed. beta-Naphthoflavone and dexamethasone were given three times: 3, 2 and 1 day before decapitation 20 mg/kg and 10 mg/kg, respectively). The highest heme oxygenase activity is observed in intact 2-week-old animals (1.16 +/- 0.038 nM/h per mg protein). Before maturity this activity decreases slightly up to the 2nd month of life. Then it stabilizes and remains virtually unchanged till the 8th month of life (1.02 +/- 0.03). Afterwards HO activity tends to increase until the 28th month of life (1.10 +/- 0.06), but does not reach the level observed in the 2-week-old animals. We have found that some typical MFO inducers can modify HO activity. While phenobarbital stimulates HO activity only in premature animals (1.42 +/- 0.056; 1.30 +/- 0.059 and 1.13 +/- 0.035, respectively in 0.5-, 1- and 2-month-old animals), beta-naphthoflavone enhances HO activity in all the groups studied. Dexamethasone, as a physiological inducer of the MFO system, modifies HO activity very characteristically. It induces this activity until the 2nd month of life and then its inducibility appears to remain unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of age, phenobarbital, beta-naphthoflavone and dexamethasone on rat hepatic heme oxygenase. 816 2

Phagocytosis of unopsonized zymosan by RAW 264.7 macrophages upregulated protein expression of haem oxygenase-1 (HO-1), inducible nitric oxide synthase (iNOS) and cyclo-oxygenase-2 (COX-2) in a time- and concentration-dependent manner. In the presence of zymosan, exogenous prostaglandin E(2) (PGE(2)) did not exert significant effects on the expression of these three enzymes. In contrast, exogenous leukotriene B(4) (LTB(4)) and LTC(4) in the nanomolar range inhibited HO-1 and iNOS expression, as well as nitrite accumulation. The COX inhibitors indomethacin and NS398 weakly inhibited HO-1 expression but had no effect on iNOS and COX-2 expression or nitrite. In contrast, the 5-lipoxygenase (5-LO) inhibitor ZM 230,487 significantly decreased HO-1, iNOS and nitrite, which were not affected by zileuton. Dexamethasone showed an inhibitory effect on HO-1 expression induced by zymosan. ZM 230,487 but not zileuton, inhibited the shift due to nuclear factor-kappaB (NF-kappaB), whereas they did not modify activator protein-1 (AP-1) binding. Our results suggest that inhibition of NF-kappaB binding could mediate the effects of ZM 230,487 on the modulation of HO-1 and iNOS protein expression. NOS inhibition by L-N(G)-nitroarginine methyl ester (L-NAME) or 1400 W abolished nitrite production and strongly reduced HO-1 expression. These results show an induction of HO-1 protein expression by zymosan phagocytosis in macrophages, with a positive modulatory role for endogenous NO and a negative regulation by exogenous LTs, likely dependent on the reduction of iNOS expression and NO production.
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PMID:Modulation of haem oxygenase-1 expression by nitric oxide and leukotrienes in zymosan-activated macrophages. 1145 66

During liver regeneration in vivo carbon monoxide (CO) and nitric oxide (NO) are supposed to play a significant role. We raise the question whether CO and NO are involved in the growth process of cultured hepatocytes. Rat hepatocytes were stimulated into proliferation, growth being estimated by DNA content, mRNA by quantitative RT-PCR, and inducible NO synthase (iNOS) activity by GC-MS. Dexamethasone proved obligatory for fast proliferation. It suppressed the spontaneous rise of iNOS-mRNA in cultures devoid of glucocorticoids, but did not counteract the rise in mRNA in actively dividing cultures. Expression of iNOS-mRNA and cell growth were further enhanced by LiCl (10 mM). NOS activity was completely suppressed by the iNOS-specific inhibitors N-(3-(aminomethyl)benzyl) acetamidine (1400 W,100 microM) and L-N(6)-(1-iminoethyl)lysine (L-NIL, 500 microM), however, without a decrease in hepatocyte growth. Proliferation was attenuated only by very high concentrations (>0.5 mM) of N-nitro-L-arginine methyl ester (L-NAME) and asymmetric dimethylarginine (ADMA). Various NO donors (at 100 microM) did not stimulate cell growth. The furoxan CAS 1609 stimulated growth, decreased iNOS-mRNA expression and transiently increased haem oxygenase-1 (HO-1)-mRNA without releasing considerable amounts of NO. 1H-[1,2,4]Oxadiazolo[4,3,-alpha]quinoxalin-1-one (ODQ) attenuated the action of CAS 1609. Proliferation was stimulated by Co-protoporphyrin and tricarbonyldichlororuthenium(II) dimer (CORM-2). We conclude that CAS 1609 triggers hepatocyte mitosis most likely via direct, NO-independent induction of HO-1 expression, pointing to CO as a growth-promoting signal in the proliferation cascade in cultured hepatocytes.
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PMID:Role of carbon monoxide and nitric oxide in adult rat hepatocytes proliferating in vitro: Effects of CAS 1609. 2061 52

Glucocorticoids are used during prostate cancer (PCa) treatment. However, they may also have the potential to drive castration resistant prostate cancer (CRPC) growth via the glucocorticoid receptor (GR). Given the association between inflammation and PCa, and the anti-inflammatory role of heme oxygenase 1 (HO-1), we aimed at identifying the molecular processes governed by the interaction between HO-1 and GR. PCa-derived cell lines were treated with Hemin, Dexamethasone (Dex), or both. We studied GR gene expression by RTqPCR, protein expression by Western Blot, transcriptional activity using reporter assays, and nuclear translocation by confocal microscopy. We also evaluated the expression of HO-1, FKBP51, and FKBP52 by Western Blot. Hemin pre-treatment reduced Dex-induced GR activity in PC3 cells. Protein levels of FKBP51, a cytoplasmic GR-binding immunophilin, were significantly increased in Hemin+Dex treated cells, possibly accounting for lower GR activity. We also evaluated these treatments in vivo using PC3 tumors growing as xenografts. We found non-significant differences in tumor growth among treatments. Immunohistochemistry analyses revealed strong nuclear GR staining in almost all groups. We did not observe HO-1 staining in tumor cells, but high HO-1 reactivity was detected in tumor infiltrating macrophages. Our results suggest an association and crossed modulation between HO-1 and GR pathways.
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PMID:Heme Oxygenase 1 Impairs Glucocorticoid Receptor Activity in Prostate Cancer. 3081 28