UMLS:C0406810 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

Query: UMLS:C0406810 (NAME)
13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An increased expression and activity of the heme oxygenase-1 (HO-1) in the liver has been observed in models of hepatic damage. Nitric oxide (NO) seems to be involved in HO-1 regulation. The aim of this work is to assess HO-1 induction and heme oxygenase (HO) activity in rats with bile duct ligation (BDL). We have assessed the effect of chronic inhibition of the NO synthesis by N(G)-nitro-l-arginine methyl ester (l-NAME) on HO-1 induction and HO activity. In the BDL animals, compared with sham-operated ones, we found an increased plasma nitrite and bilirubin concentration, and a marked liver expression of inducible nitric oxide synthase and HO-1, assessed by both Western blot and immunohistochemistry. Chronic l-NAME treatment prevented plasma nitrite increase in animals subjected to BDL. BDL animals treated with l-NAME, compared with untreated BDL rats, showed an important decrease in HO-1 expression and in HO activity (assessed as a decreased plasma bilirubin and bilirubin excretion). In conclusion, our experiments show parallel changes in expression and activity of HO-1 and NOS2 activity in the BDL model of liver damage and suggest that increased NO production is involved in HO-1 overexpression.
...
PMID:Relationships between NOS2 and HO-1 in liver of rats with chronic bile duct ligation. 1590 18

Pregnancy is associated with attenuated vascular reactivity to a variety of contractile agonists. Heme oxygenases are expressed in the placenta, and it has been suggested that the heme oxygenase/carbon monoxide (HO/CO) pathway plays a significant role in regulating blood flow through the feto-placental unit. In this study we investigated the possible involvement of heme oxygenases in the reduced vascular reactivity associated with pregnancy. Arginine vasopressin (AVP) (10(-10)-3x10(-7) M) induced concentration-dependent contraction of aortic ring segments from non-pregnant and pregnant (16-19 days) rats. Pregnancy did not alter the sensitivity to AVP (pD2=8.5+/-0.1 and pD2=8.4+/-0.2 in non-pregnant and pregnant rats, respectively) but significantly reduced the maximum response (107.9+/-12.7% and 38.6+/-7.4%, respectively, relative to noradrenaline-induced contraction). Western blot analysis revealed the expression of HO-2 but not HO-1 isoform in both groups. There was a significant increase in the expression and activity of HO-2 protein in aortic tissues from pregnant rats compared with those from age-matched non-pregnant rats. In the presence of L-NAME to inhibit nitric oxide (NO) synthesis, tin protoporphyrin IX (SnPP-IX, 10(-5) M), an inhibitor of heme oxygenase, did not significantly affect AVP-induced contraction in aorta segments from pregnant and non-pregnant rats. It was concluded that, though pregnancy increased the expression and activity of HO-2 in the aorta, HO-2 was not involved in the attenuated response to AVP.
...
PMID:Increased expression and activity of heme oxygenase-2 in pregnant rat aorta is not involved in attenuated vasopressin-induced contraction. 1627 49

To explore the underlying mechanism(s) of pulmonary arterial hypertension in endotoxic shock, the roles of N-acetylcysteine (NAC), nitric oxide (NO) and carbon monoxide (CO) were investigated. Pulmonary arterial rings (3-mm width) were prepared from 24 rabbits. Lipopolysaccharide (LPS), after 7-hour incubation, decreased the endothelium-dependent relaxation response of the arterial ring (pre-contracted with phenylephrine) to acetylcholine (1 mumol/L), but did not affect the endothelium-independent relaxation response to sodium nitroprusside. The LPS effects were reduced by a concomitant incubation with the free radical scavenger (NAC), NO donor (L-arginine), and CO donor (hemin), respectively. On the other hand, the LPS effects were enhanced by applying heme oxygenase-1 (HO-1) inhibitor (zinc protoporphyrin) to block CO production. The response to acetylcholine changed from relaxation to contraction, however, the contractile response to phenylephrine increased significantly after pre-incubation with nitric oxide synthase (NOS) inhibitor (L-NAME) to block NO production, confirming the importance of CO and NO. These results show that LPS impairs endothelium-dependent relaxation of the pulmonary artery, which can be greatly reduced by the antioxidant, or by supplying with NO and CO. Thus, multiple factors are involved in this model of endotoxin-induced pulmonary hypertension.
...
PMID:Multiple factors contributing to lipopolysaccharide-induced reactivity changes in rabbit pulmonary artery. 1634 99

The long-term effects of nitric oxide (NO) on cell susceptibility to photodynamic killing have been studied, using a human breast tumor line (COH-BR1). Subconfluent cells were exposed to a nonlethal dose of spermine NONOate (SPNO, 0.2 mM) and 20 h later were metabolically sensitized with protoporphyrin IX (PpIX) by incubating with 5-aminolevulinic acid. PpIX overproduced in mitochondria was allowed to diffuse to peripheral sites, including plasma membrane, after which a photooxidative challenge was imposed. Active (but not decomposed) SPNO made cells substantially more resistant to necrotic photokilling than non-SPNO-treated controls. A similar response to a tert-butyl hydroperoxide challenge was observed. Hyperresistance was detected approximately 8 h post-SPNO, maximized after approximately 20 h, and reflected diminished oxidant accumulation, as determined with 2',7'-dichlorofluorescein. Intracellular free iron determined with the fluorescent probe calcein rose to approximately 160% of the control level 6 h after SPNO, but declined to approximately 70% after 24 h. Immunoblot analyses revealed a rapid early (approximately 2 h post-NO) increase in heme oxygenase-1 level, followed by a gradual (4-20 h post-NO) increase in ferritin. Upregulation of these proteins is consistent with a cytoprotective mechanism involving mobilization of "signaling" iron. Preactivated RAW 264.7 macrophages on microporous inserts also induced a long-term photoresistance in underlying PpIX-sensitized COH-BR1 cells. This response was abolished by L-NAME, indicating that NO from induced nitric oxide synthase was involved. The NO effects described are entirely novel in the context of photooxidative stress and provide new insights into how NO might affect antitumor photodynamic therapy (PDT).
...
PMID:Nitric oxide-induced resistance to lethal photooxidative damage in a breast tumor cell line. 1663 22

We investigated here the effect of l-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial aging. Endothelial cells were cultured in medium containing 70micromol/L arginine until fourteenth passage. ADMA, dl-homocysteine, and l-arginine were replaced every 48h starting at the fourth passage. ADMA or homocysteine inhibited significantly the population doublings (PD) and accelerated the process of aging. Co-incubation with l-arginine enhanced PD, inhibited senescence associated beta-galactosidase activity, and increased telomerase activity. This effect was associated with an increase in NO synthesis and NO synthase protein expression. Furthermore, l-arginine-induced NO formation was accompanied by a reduction in oxidative stress and an increase in protein expression and enzyme activity of heme oxygenase (HO)-1. The NO synthase inhibitor l-NAME completely abolished the effect of l-arginine on ADMA or homocysteine-accelerated aging. These findings demonstrate that l-arginine prevents the onset of endothelial aging in ADMA or homocysteine-treated cells by increasing NO formation and consequently the induction of HO-1. This might provide a new strategy to delay ADMA or homocysteine-accelerated aging.
...
PMID:Effect of L-arginine on asymmetric dimethylarginine (ADMA) or homocysteine-accelerated endothelial cell aging. 1671 97

The development of carbon monoxide-releasing molecules (CO-RMs) in recent years helped to shed more light on the diverse range of anti-inflammatory and cytoprotective activities of CO gas. In this study, we examined the effect of a ruthenium-based water-soluble CO carrier (CORM-3) on lipopolysaccharide (LPS)- and interferon-gamma (INF-gamma)-induced inflammatory responses in BV-2 microglial cells and explored the possible mechanisms of action. BV-2 microglial cells were stimulated with either LPS or INF-gamma in the presence of CORM-3 and the inflammatory response evaluated by assessing the effect on nitric oxide production (nitrite levels) and tumor necrosis factor-alpha (TNF-alpha) release. Similar experiments were also performed in the presence of inhibitors of guanylate cyclase (ODQ), NO synthase (L-NAME), heme oxygenase activity (tin protoporphyrin IX) or various mitogen-activated protein kinase (MAPK) inhibitors. CORM-3 significantly attenuated the inflammatory response to LPS and INF-gamma as evidenced by a significant reduction (p < 0.001) in nitrite levels and TNF-alpha production (P < 0.05). Such effect was maintained in the presence of ODQ, L-NAME or tin protoporphyrin without showing any cytotoxicity. The use of an inactive form of CORM-3 that does not contain carbonyl groups (Ru(DMSO)(4)Cl(2) failed to inhibit the increase in inflammatory markers suggesting that liberated CO mediates the observed effects. In addition, inhibition of phosphatidylinositol-3-phosphate kinase (PI3K) and extracellular signal-regulated kinase (ERK) pathways seemed to amplify the anti-inflammatory effect of CORM-3, particularly in cells stimulated with INF-gamma. These results suggest that the anti-inflammatory action of CORM-3 could be exploited to mitigate microglia activation in neuro-inflammatory diseases.
...
PMID:A carbon monoxide-releasing molecule (CORM-3) attenuates lipopolysaccharide- and interferon-gamma-induced inflammation in microglia. 1733 83

The trigger for liver regeneration, including shear stress, has been the subject of ongoing debate. Blood vessel-derived gaseous molecules carbon monoxide (CO) and nitric oxide (NO) regulate vascular tone and play an important role in liver regeneration. In heme oxygenase-1 (HO-1) transgenic mice, it has been shown that CO-mediated impairment of vasorelaxation is an NO-dependent event. We therefore studied liver regeneration in HO-1 overexpressing animals in dependency of NO availability. Mice were subjected to (2/3) hepatectomy and were treated with either cobalt protoporphyrin-IX for induction of CO-liberating HO-1, N(omega)-nitro-L-arginine methyl ester (L-NAME) for blockade of NO synthase (NOS) or both. Application of molsidomine in L-NAME treated animals served for resubstitution of NO. Vehicle-treated animals served as respective control animals. We examined 5-bromo-2'-deoxyuridine incorporation and proliferating cell nuclear antigen expression as well as HO-1 and NOS-2 protein levels. Intrahepatic red blood cell velocity and volumetric blood flow were evaluated by in vivo fluorescence microscopy as indicators for microvascular shear stress. Hepatic regeneration remained unaffected by L-NAME application for NOS blockade. However, NOS blockade in HO-1 induced animals caused increased 5-bromo-2'-deoxyuridine and proliferating cell nuclear antigen measures of liver regeneration. In parallel, these animals revealed increased velocities and volumetric blood flow in the terminal afferent vessels and postsinusoidal venules. These local hemodynamic changes including enhanced hepatocyte proliferation could be reversed by NO liberation via molsidomine. The present findings stress the role of NO to counterbalance vascular tone in HO-1 overexpressing animals for maintenance of adequate perfusion and salutary shear force within the hepatic microvasculature upon liver resection.
...
PMID:NO counterbalances HO-1 overexpression-induced acceleration of hepatocyte proliferation in mice. 1740 37

Previous studies have described the magnitude and time course by which several genes are regulated within exercising skeletal muscle. These include interleukin-6 (IL-6), interleukin-8 (IL-8), heme oxygenase-1 (HO-1), and heat shock protein-72 (HSP72), which are involved in secondary signaling and preservation of intracellular environment. However, the primary signaling mechanisms coupling contraction to transcription are unknown. We hypothesized that exercise-induced nitric oxide (NO) production is an important signaling event for IL-6, IL-8, HO-1, and HSP72 expression in muscle. Twenty healthy males participated in the study. By real-time PCR, mRNA levels for 11 genes were determined in thigh muscle biopsies obtained 1) before and after 2 h knee extensor exercise without (control) and with concomitant NO synthase inhibition (nitro-L-arginine methyl ester, L-NAME, 5 mg x kg(-1)); or 2) before and after 2 h femoral artery infusion of the NO donor nitroglycerin (NTG, 1.5 microg x kg(-1) x min(-1)). L-NAME caused marked reductions in exercise-induced expression of 4 of 11 mRNAs including IL-6, IL-8, and HO-1. IL-6 protein release from the study leg to the circulation increased in the control but not in the L-NAME trial. NTG infusion significantly augmented expression of the mRNAs attenuated by L-NAME. These findings advance the novel concept that NO production contributes to regulation of gene expression in muscle during exercise. Subsequently, we sought evidence for involvement of AMP-activated kinase or nuclear factor kappa B, but found none.
...
PMID:Nitric oxide production is a proximal signaling event controlling exercise-induced mRNA expression in human skeletal muscle. 1747 May 70

LCY-2-CHO has anti-inflammatory actions on macrophages. To understand its therapeutic implication in atherosclerosis, we examined its effects on the expressions of anti-inflammatory and inflammatory proteins in cultured rat aortic vascular smooth muscle cells (VSMC). LCY-2-CHO is able to induce heme oxygenase-1 (HO-1) protein expression through a transcriptional action. The HO-1 inducting effect of LCY-2-CHO was inhibited by SB203580, N(G)-nitro-l-arginine methylester (l-NAME), and wortmannin, but was not affected by U0126 or SP600125. In accordance LCY-2-CHO increased protein phosphorylation of p38, Akt, and eNOS. Nrf2 is a transcription factor essential for HO-1 gene induction and we showed that LCY-2-CHO is able to cause Nrf2 nuclear translocation and this action depends on p38, Akt and eNOS. In addition to induce anti-inflammatory HO-1, LCY-2-CHO reduced interleukin-1beta (IL-1beta)-induced inflammatory mediators, inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), growth-related oncogene protein-alpha (GRO-alpha), and interleukin-8 (IL-8). Inhibitory effect on IL-1beta-mediated NF-kappaB activation was evidenced by the diminishment of IkappaB kinase (IKK) phosphorylation and IkappaBalpha degradation. In contrast, IL-1beta-mediated ERK and JNK activations were not changed by LCY-2-CHO, while p38 activation by IL-1beta and LCY-2-CHO displayed the non-additivity. Taken together, given the overall anti-inflammatory properties of LCY-2-CHO in VSMC, in terms to induce HO-1 gene expression and inhibit inflammatory gene expression, these results highlight the therapeutic potential of LCY-2-CHO in atherosclerosis.
...
PMID:The anti-inflammatory actions of LCY-2-CHO, a carbazole analogue, in vascular smooth muscle cells. 1749 20

The present study was designed to investigate the effect of lipopolysaccharide (LPS) on the expression levels and activities of the nitric oxide synthase (NOS) and heme oxygenase (HO) systems in the rat adrenal gland. Both enzymatic activities were significantly increased in this tissue after in vivo treatment with LPS. The concurrent induction of the HO-1, NOS-1, and NOS-2 gene products was also detected as both mRNAs and protein levels were augmented by this treatment in a time-dependent way. A significant interaction between both signaling systems was also demonstrated as in vivo blockage of NOS activity with N(G)-nitro-L-arginine methyl ester (L-NAME) resulted in a significant reduction in HO expression and activity levels, while an increase in NOS activity was observed when HO was inhibited by Sn-protoporphyrin IX (Sn-PPIX). As both NOS and HO activities have been previously involved in the modulation of adrenal steroidogenesis, we investigated the participation of these signaling systems in the adrenal response to LPS. Our results showed that acute stimulation of steroid production by ACTH was significantly increased when either NOS or HO activities were inhibited. We conclude that adrenal NOS and HO can be induced by a non-lethal dose of endotoxin supporting a modulatory role for these activities in the adrenal response to immune challenges.
...
PMID:Induction of nitric oxide synthase and heme oxygenase activities by endotoxin in the rat adrenal cortex: involvement of both signaling systems in the modulation of ACTH-dependent steroid production. 1759 16

<< Previous 1 2 3 4 5 6 7 8 Next >>