Metabolic Regulation of Heme Catabolism and Bilirubin Production. I. HORMONAL CONTROL OF HEPATIC HEME OXYGENASE ACTIVITY

Bakken, A.; Thaler, Michael; Schmid, Rudi

doi:10.1172/jci106841

Cited by 144 publications

(45 citation statements)

References 33 publications

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“…It has been reported that hepatic HO activity is induced in vivo by glucagon, insulin and epinephrine (Bakken et al 1972), while human chorionic gonadotropin increases this parameter in rat testis (Kutty & Maines 1989). Moreover, glucagon and angiotensin II induce HO-1 expression in hepatic and kidney cells respectively (Immenschuh et al 1998, Haugen et al 2000.…”

Section: Discussionmentioning

confidence: 97%

Adrenocorticotropin induces heme oxygenase-1 expression in adrenal cells

Pomeraniec

Grion²,

Gadda³

et al. 2004

Journal of Endocrinology

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Heme oxygenase (HO) catalyzes the first and ratecontrolling step of heme catabolism into biliverdin, iron and carbon monoxide. Three isoforms of HO have been identified so far: the inducible HO-1 and the constitutive HO-2 and HO-3. Both HO-1 and HO-2 were expressed in zona fasciculata (ZF) adrenal cells and in a mouse adrenocortical cell line (Y1). HO-1 but not HO-2 expression was upregulated by adrenocorticotropic hormone (ACTH) and accumulation of HO-1 protein correlated with an increase in HO activity in Y1 cells. ACTH induced HO-1 expression in a time-and dose-dependent manner with a maximum after 5 h of treatment and a threshold concentration of 0·1 mIU/ml. Actinomycin D and cycloheximide completely blocked the effect of ACTH on HO-1 mRNA expression whereas mRNA stability was not affected by ACTH. Permeable analogs of cAMP mimicked the effect of ACTH on HO-1 expression and ACTH induction was prevented by the protein kinase A (PKA) inhibitor H89. Steroid production was significantly increased when both HO-1 and HO-2 activities were inhibited by Sn-protoporphyrin IX (SnPPIX). The lipid peroxidation and increase in carbonyl content triggered by hydrogen peroxide was prevented by treatment of Y1 cells with bilirubin and ACTH.

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Section: Discussionmentioning

confidence: 97%

Adrenocorticotropin induces heme oxygenase-1 expression in adrenal cells

Pomeraniec

Grion²,

Gadda³

et al. 2004

Journal of Endocrinology

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“…For example, HO-1 activity in liver and spleen is rapidly increased in rats after intraperitoneal injection of niacin. 22,23 Dietary supplementation with niacin also increases hepatic HO-1 mRNA levels in rats. 30 In humans, long-term oral administration of niacin at pharmacological doses increases serum bilirubin levels by Ϸ9%.…”

Section: Discussionmentioning

confidence: 99%

“…15 Intravenous and long-term oral administration of niacin elevates serum bilirubin levels 19 -21 by complex mechanisms that include increased splenic and hepatic HO-I activity. 22,23 Given that bilirubin has known cardioprotective effects, we hypothesized that its formation downstream of HO-1 induction by niacin may explain some of the lipid-independent cardioprotective properties of the drug.…”

Section: Clinical Perspective On P 158mentioning

confidence: 99%

Niacin Inhibits Vascular Inflammation via the Induction of Heme Oxygenase-1

Chen²,

Barter³

et al. 2012

Circulation

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Background-Heme oxygenase-1 (HO-1) is a cytoprotective protein whose expression is consistently associated with therapeutic benefits in a number of pathological conditions such as atherosclerotic vascular disease and inflammation. Niacin is a pleiotropic drug that slows the progression of coronary artery disease and increases serum levels of the HO-1 enzymatic product bilirubin. This study asks if the cardioprotective properties of niacin involve the induction of HO-1. Methods and Results-New Zealand White rabbits received chow or chow supplemented with 0.6% (wt/wt) niacin for 2 weeks. Acute vascular inflammation was induced in the animals by placing a nonocclusive silastic collar around the left common carotid artery. At 24 hours after collar implantation, serum bilirubin and vascular, liver, and spleen HO-1 messenger RNA levels were significantly increased. Vascular inflammation was decreased in the niacin-supplemented animals compared with control. Treatment of the animals with tin protoporphyrin-IX, a global HO inhibitor, or HO-1 small interfering RNA to knock down carotid artery HO-1 attenuated the ability of niacin to inhibit vascular inflammation. Treatment of cultured human coronary artery endothelial cells with niacin increased HO-1 expression by activating the nuclear factor-E2-related factor 2/p38 mitogen-activated protein kinase signaling pathway and inhibiting tumor necrosis factor ␣-induced endothelial inflammation. The antiinflammatory effects of niacin in human coronary artery endothelial cells were mimicked by bilirubin and abolished by incubation with tin protoporphyrin-IX and knock down of nuclear factor-E2-related factor 2. Conclusions-Niacin

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“…Hypoglycemia, induced by injection of insulin or mannose, was a powerful stimulator of HO (7-fold increase). The coinjection of insulin and glucose abolished this effect (Bakken et al, 1972).…”

Section: Hormonal Regulationmentioning

confidence: 95%