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)

We examined the role of heme oxygenase (HO)-1 in morphine-induced decrease in macrophage migration. Morphine promoted expression of HO-1 in murine macrophages. Morphine-receiving mice (MRCs) showed decreased (P<.001) macrophage migration and increased (P<.001) occurrence of macrophage apoptosis. In in vitro studies, peritoneal macrophages harvested from MRCs also showed decreased (P<.001) migration, compared with those from control mice. Bone marrow cells isolated from MRCs showed not only decreased (P<.001) migration but also increased apoptosis. Pretreatment of MRCs with hemin not only decreased migration of macrophages further but also enhanced the apoptosis of peritoneal macrophages. On the other hand, pretreatment of MRCs with zinc protoporphyrin attenuated the effect of morphine on both macrophage migration and the occurrence of apoptosis. In in vitro studies, pretreatment of macrophages with hemin exacerbated morphine-induced apoptosis, whereas pretreatment with zinc protoporphyrin attenuated morphine-induced macrophage apoptosis.
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PMID:Role of heme oxygenase-1 in morphine-modulated apoptosis and migration of macrophages. 1250 45

Opiate addiction has been reported to contribute to the progression of renal injury. In addition, opiate addiction is a major risk factor for the development of human immunodeficiency virus-associated nephropathy. In the present study, we evaluated the effects of morphine, an active metabolite of heroin, on glomerular epithelial cell (GEC) growth and the involved molecular mechanism. At lower concentrations, morphine promoted GEC proliferation; however, at higher concentrations, morphine triggered apoptosis. Antioxidants inhibited morphine-induced proliferation as well as apoptosis. Similarly, free radical scavengers prevented morphine-induced GEC proliferation and apoptosis. Because proliferative and proapoptotic effects of morphine were inhibited by free radical scavengers as well as antioxidants, it appears that these effects of morphine are mediated through oxidative stress. Hemin, an inducer of heme oxygenase (HO) activity, inhibited GEC proliferation and promoted GEC apoptosis under basal and morphine-stimulated conditions. On the other hand, zinc protoporphyrin, an inhibitor of HO activity, promoted GEC proliferation and inhibited GEC apoptosis under basal as well as morphine-stimulated conditions. These findings suggest that HO activity is directly related to GEC apoptosis and inversely related to GEC proliferation. Morphine, de novo, had bimodal effects on HO activity: lower concentrations increased and higher concentrations decreased HO activity. It appears that HO activity may be modifying morphine-induced GEC growth.
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PMID:Role of oxidative stress and heme oxygenase activity in morphine-induced glomerular epithelial cell growth. 1281 15

Occurrence of macrophage apoptosis has been implicated for the altered immune function found in an opiate milieu. In the present study, we evaluated the role of oxidative stress in morphine-induced macrophage apoptosis. Morphine promoted the apoptosis of macrophages. This effect of morphine was associated with the production of superoxide and nitric oxide (NO). Antioxidants provided protection against morphine-induced macrophage injury. In addition, diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, attenuated the proapoptotic effect of morphine. Antitransforming growth factor-beta (anti-TGF-beta) antibody and propranolol (an inhibitor of the phospholipase D pathway) inhibited morphine-induced superoxide generation as well as apoptosis. N'-Tetraacetic acid tetra (acetoxymethyl) ester, a calcium-chelating agent, inhibited morphine-induced apoptosis, whereas thapsigargin (a calcium agonist) stimulated macrophage apoptosis under basal as well as morphine-stimulated states. These studies suggest that morphine-induced macrophage apoptosis is mediated through downstream signaling involving TGF-beta and NO production. Moreover, there is NADPH oxidation activation involving phospholipase D and Ca(2+), leading to the generation of superoxide. In in vivo studies, administration of N-acetyl cysteine and preinduction of heme oxygenase activity and epoetin alpha prevented morphine-induced peritoneal macrophage apoptosis, thus further confirming the role of oxidative stress in morphine-induced macrophage apoptosis.
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PMID:Morphine-induced macrophage apoptosis: oxidative stress and strategies for modulation. 1503 69