Stimulation of heme oxygenase in macrophages and liver by endotoxin.

Gemsa, Diethard; Woo, C. H.; Fudenberg, H. Hugh; Schmid, Rudi

doi:10.1172/jci107599

Cited by 58 publications

(25 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is interesting to note that the activity of heme oxygenase, which is the rate-limiting enzyme in bilirubin formation, has been shown to be increased in animals deprived of ascorbate (25). In addition, heme oxygenase is induced by a number of conditions known to exert an oxidative stress, including exposure of rats to certain metal ions (26), sulfhydryl reactive compounds (27,28), and endotoxin (29), as well as depriving mice of selenium (30). Cigarette smoking, known to be associated with enhanced production of oxygen and carbon-centered radicals (31), significantly lowers plasma levels of bilirubin in humans (32).…”

Section: Resultsmentioning

confidence: 99%

Antioxidant activity of albumin-bound bilirubin.

Stocker¹,

Glazer²,

Ames³

1987

Proc. Natl. Acad. Sci. U.S.A.

668

410

View full text Add to dashboard Cite

Bilirubin, when bound to human albumin and at concentrations present in normal human plasma, protects albumin-bound linoleic acid from peroxyl radical-induced oxidation in vitro. Initially, albumin-bound bilirubin (Alb-BR) is oxidized at the same rate as peroxyl radicals are formed and biliverdin is produced stoichiometrically as the oxidation product. On an equimolar basis, Alb-BR successfully competes with uric acid for peroxyl radicals but is less efficient in scavenging these radicals than vitamin C. These results show that 1 mol of Alb-BR can scavenge 2 mol of peroxyl radicals and that small amounts of plasma bilirubin are sufficient to prevent oxidation of albumin-bound fatty acids as well as of the protein itself. The data indicate a role for Alb-BR as a physiological antioxidant in plasma and the extravascular space.

show abstract

Section: Resultsmentioning

confidence: 99%

Antioxidant activity of albumin-bound bilirubin.

Stocker¹,

Glazer²,

Ames³

1987

Proc. Natl. Acad. Sci. U.S.A.

668

410

View full text Add to dashboard Cite

show abstract

“…In addition to the primary role HO-1 plays in heme catabolism, HO-1 aids in cytoprotection from various xenobiotic and endobiotic insults. In fact, HO-1 expression is induced by heme, as well as by a variety of non-heme inducers, such as hydrogen peroxide, ultraviolet (UV) irradiation, cadmium (Keyse and Tyrrell 1989), endotoxin (Gemsa et al 1974), or nitric oxide (Marquis and Demple 1998).…”

mentioning

confidence: 99%

Hepatocyte-Specific Deletion of Heme Oxygenase-1 Disrupts Redox Homeostasis in Basal and Oxidative Environments

Mamiya

Katsuoka

Hirayama

et al. 2008

Tohoku J. Exp. Med.

View full text Add to dashboard Cite

Heme oxygenase-1 (HO-1) is the rate-limiting enzyme of heme catabolism and has been assumed to be important in cellular response against oxidative stress through modification of the pro-oxidant heme into less toxic catabolites that behave as antioxidants. However, the precise mechanisms involved and the physiological significance of such activity remain to be clarified. To elucidate roles HO-1 plays in vivo, hepatocyte-specific conditional knockout (CKO) mice of HO-1 gene were generated by site-specific recombination using albumin-promoter-driven Cre-loxP system. In livers of HO-1 CKO mice HO-1 protein level decreased to approximately 30% of control mouse livers. The HO-1 CKO mice are viable, exhibit normal growth curves over six months, and show no histological and serological abnormalities. We found that several cytoprotective genes, such as NAD(P)H dehydrogenase quinone 1 and glutathione S-transferase P1, showed markedly elevated expression, suggesting the increase of oxidative stress in HO-1 CKO mice even under quiescent conditions. In vivo electron paramagnetic resonance studies demonstrated that signal decay times of nitroxyl radicals were significantly longer in livers of HO-1 CKO mice than that of control mice, indicating that radical scavenging activity was significantly compromised in the mutant liver. HO-1 CKO mice were susceptible to carbon tetrachloride hepatotoxicity. These results provide the first in vivo evidence that HO-1 acts to protect cells against the oxidative stress in both basal conditions and upon chemical insult.heme oxygenase-1; oxidative stress; reactive oxygen species; in vivo EPR; carbon tetrachloride. Tohoku

show abstract

“…The released hemoglobin would neutralize the NO by the rapid, irreversible reaction leading to methemoglobin and nitrate. The nitrate would be disposed of through the kidneys and the gut, and the methemoglobin would be broken down by macrophages through the action of heme oxygenase [30,31], which also suppresses the induction of cytokines.…”

Section: A Relationship Between Disseminated Intravascular Coagulatiomentioning

confidence: 99%

Is Cholesterol Sulfate Deficiency a Common Factor in Preeclampsia, Autism, and Pernicious Anemia?

Seneff

Davidson²,

Liu

2012

Entropy

View full text Add to dashboard Cite

Abstract:In a recent paper, we proposed that a contributing factor in autism is a deficiency in cholesterol sulfate supply. In this paper, we investigate a link between preeclampsia and subsequent autism in the child, and we hypothesize that both conditions can be attributed to a severe depletion of cholesterol sulfate. Through studies on the Vaccine Adverse Event Reporting System (VAERS) database, we demonstrate a strong statistical relationship among the signs and symptoms associated with autism and those associated with preeclampsia, pernicious anemia, and serious adverse reactions to vaccines. We show that VAERS reports associated with symptoms typical of pernicious anemia produce both a set of symptoms that are highly correlated with preeclampsia and another set highly correlated with autism. We explain this observation via an argument that, in a severe reaction, the cascade of events subsequent to vaccination reflects a profuse production of nitric oxide (NO) and consequential destruction of both red blood cells (RBCs) and cobalamin. This may explain the diverse signs and symptoms associated with both preeclampsia and severe vaccine adverse reactions. We argue that excess NO synthesis, induced by the aluminum and antigen in vaccines, results in hemolysis of RBCs, which allows hemoglobin to scavenge the excess NO, converting it to nitrate. The NO is also scavenged by cobalamin, leading to its inactivation and contributing to subsequent pernicious anemia. Finally, we demonstrate that severe adverse reactions to vaccines can be associated with life-threatening conditions related to the heart and brain, as well as OPEN ACCESSEntropy 2012, 14 2266 stillbirth, when the vaccine is administered to a woman in the third-trimester of pregnancy, as demonstrated by statistical analysis of the Gardasil records.

show abstract

Stimulation of heme oxygenase in macrophages and liver by endotoxin.

Cited by 58 publications

References 23 publications

Antioxidant activity of albumin-bound bilirubin.

Antioxidant activity of albumin-bound bilirubin.

Hepatocyte-Specific Deletion of Heme Oxygenase-1 Disrupts Redox Homeostasis in Basal and Oxidative Environments

Is Cholesterol Sulfate Deficiency a Common Factor in Preeclampsia, Autism, and Pernicious Anemia?

Contact Info

Product

Resources

About