Nutraceutical induction and mimicry of heme oxygenase activity as a strategy for controlling excitotoxicity in brain trauma and ischemic stroke: focus on oxidative stress

2020 ◽  
pp. 1-12
Author(s):  
Mark F McCarty ◽  
Aaron Lerner
Keyword(s):  
Oxidative Stress ◽  
Ischemic Stroke ◽  
Heme Oxygenase ◽  
Brain Trauma ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity

scholarly journals The role of heme oxygenase in metastatic melanoma tumorigenicity

2015 ◽  
Author(s):  
◽  
Kimberly J. Jasmer
Keyword(s):  
Oxidative Stress ◽  
Metastatic Melanoma ◽  
Heme Oxygenase ◽  
Focal Adhesion ◽  
Target Genes ◽  
Cancer Development ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity ◽  
Receptor Interactions

Reactive oxygen species (ROS) are highly reactive, tumorigenic molecules. In response to ROS accumulation, or oxidative stress, the transcription factor Nrf2 promotes expression by binding antioxidant response elements (AREs) found in the promoter of target genes. Traditionally, Nrf2 has been considered inhibitory of cancer by promoting the expression of phase II detoxifying enzymes, drug transporters, anti-apoptotic proteins, and proteasomes, which facilitate the removal of ROS and promote cell survival. Recently, however, overexpression of Nrf2-target genes has been implicated in promoting several cancer hallmarks and facilitating cancer development. Significant focus has been given to the role of Keap1/Nrf2 as a sensor for oxidative stress. Much less attention has been paid to the role of Bach1, a transcriptional repressor that competes with Nrf2 for ARE binding. The best-characterized Bach1 target is Heme Oxygenase-1 (HMOX1). While heme oxygenase inhibits cancer by preventing ROS-induced damage, mounting evidence suggests that HMOX1 overexpression at later stages in cancer development may promote cancer progression. Heme oxygenase catalyzes the degradation of heme and has two isozymes. HMOX1 is inducible by heme and oxidative stress while HMOX2 is constitutively expressed. Stage IV metastatic melanoma has a median survival of only 6 to 10 months. Unfortunately, current therapeutic approaches provide limited benefit in overall survival, highlighting the need for the identification of novel therapeutic targets. Activating mutations in B-Raf are found in approximately 70% of malignant melanomas. Using an anchorage-independent melanosphere assay, which is indicative of the tumorigenicity of melanoma cells, we found that activation of B-Raf, but not N-Ras, is a driver of melanosphere formation. We provide evidence that derepression of Bach1 by treatment with cobalt protoporphyrin IX (CoPP) is sufficient for melanosphere formation, and that melanosphere formation induced by either CoPP treatment or B-Raf activation is dependent on heme oxygenase activity. Global transcriptome analysis revealed enrichment for genes involved in focal adhesion and extracellular matrix (ECM)-receptor interactions following either B-Raf activation or treatment with CoPP. We propose a mechanism by which heme oxygenase promotes melanosphere formation, and by extension, enhanced tumorigenicity, by modulating expression of genes involved in focal adhesion and ECM-receptor interactions. Heme oxygenase activity may provide a novel therapeutic target for the treatment of metastatic melanoma.

NO-mediated activation of heme oxygenase: endogenous cytoprotection against oxidative stress to endothelium

1996 ◽  
Vol 270 (1) ◽  
pp. H107-H114 ◽  
Author(s):  
R. Motterlini ◽  
R. Foresti ◽  
M. Intaglietta ◽  
R. M. Winslow
Keyword(s):  
Oxidative Stress ◽  
Hydrogen Peroxide ◽  
Endothelial Cells ◽  
Heme Oxygenase ◽  
Stress Protein ◽  
No Synthase ◽  
Protective Effects ◽  
Cyclic Monophosphate ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity

We investigated the effect of nitric oxide (NO) on the induction of the stress protein heme oxygenase and its protective role in vascular endothelial cells exposed to hydrogen peroxide. Treatment of porcine aortic endothelial cells for 6 h with the NO-releasing compounds (0.1-1 mM) sodium nitroprusside (SNP), S-nitroso-N-acetylpenicillamine (SNAP), and 3-morpholinosydnonimine (SIN-1) resulted in a concentration-dependent increase in heme oxygenase activity. At 1 mM, the activity of heme oxygenase was augmented 8.5-fold with SNP, 5.8-fold with SNAP, and 5.7-fold with SIN-1 over the control value. In contrast, endothelial cells exposed to 100 microM S-bromoguanosine 3',5'-cyclic monophosphate, a tissue-permeable analogue that mimics the action of guanosine 3',5'-cyclic monophosphate, did not show any change in heme oxygenase activity. Activation of the inducible NO synthase by the synergistic action of bacterial lipopolysaccharide (250 ng/ml) and interferon-gamma (100 U/ml) also increased endothelial heme oxygenase activity by 3.2-fold (P < 0.05 vs control). Methylene blue (1 microM), an inhibitor of both NO synthase and guanylate cyclase activities, completely abolished this effect. Cells previously exposed to SNAP and SIN-1 exhibited a significant protection against the cytotoxicity mediated by hydrogen peroxide (250 microM) (P < 0.05). Conversely, SNP did not show any protective effects, possibly because of catalytic iron released during its chemical decomposition. In fact, the iron chelator deferoxamine (5 mM) completely suppressed the SNP-mediated cytotoxicity and partially attenuated the activity of heme oxygenase to a level equal to that mediated by SIN-1 and SNAP. These results indicate that NO is a determinant in the modulation of the activity of heme oxygenase leading to a major resistance of the endothelium to oxidative stress.

scholarly journals Early induction of oxidative stress in a mouse model of Alzheimer’s disease with heme oxygenase activity

2014 ◽  
Vol 10 (2) ◽  
pp. 599-604 ◽  
Author(s):  
SANLI XING ◽  
DINGZHU SHEN ◽  
CHUAN CHEN ◽  
JIAN WANG ◽  
ZHIHUA YU
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Mouse Model ◽  
Heme Oxygenase ◽  
Heme Oxygenase Activity ◽  
Model Of Alzheimer’S Disease ◽  
Oxygenase Activity

Heme oxygenase activity and oxidative stress signaling in soybean leaves

Plant Science ◽  
2006 ◽  
Vol 170 (2) ◽  
pp. 339-346 ◽  
Author(s):  
K.B. Balestrasse ◽  
G.O. Noriega ◽  
A. Batlle ◽  
M.L. Tomaro
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Stress Signaling ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity ◽  
Soybean Leaves ◽  
And Oxidative Stress

Determination of Heme Oxygenase Activity in Murine Macrophages for Studying Oxidative Stress Inhibitors

1998 ◽  
Vol 263 (2) ◽  
pp. 251-253 ◽  
Author(s):  
Victor Turcanu ◽  
Mounir Dhouib ◽  
Philippe Poindron
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Murine Macrophages ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity

Effects of the environmental pollutants on heme oxygenase activity and cytochrome P-450 content in fish

1990 ◽  
Vol 44 (2) ◽  
pp. 189-196 ◽  
Author(s):  
Toshihiko Ariyoshi ◽  
Seiichi Shiiba ◽  
Hiroyuki Hasegawa ◽  
Koji Arizono
Keyword(s):  
Heme Oxygenase ◽  
Environmental Pollutants ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity ◽  
Cytochrome P 450

Heme oxygenase activity in the internal anal sphincter: Effects of nonadrenergic, noncholinergic nerve stimulation

2000 ◽  
Vol 118 (3) ◽  
pp. 477-486 ◽  
Author(s):  
Sushanta Chakder ◽  
Gao-Yuan Cao ◽  
Richard B. Lynn ◽  
Satish Rattan
Keyword(s):  
Anal Sphincter ◽  
Heme Oxygenase ◽  
Nerve Stimulation ◽  
Internal Anal Sphincter ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity

scholarly journals Suppression of hyperbilirubinemia in the rat neonate by chromium-protoporphyrin. Interactions of metalloporphyrins with microsomal heme oxygenase of human spleen.

1982 ◽  
Vol 156 (6) ◽  
pp. 1878-1883 ◽  
Author(s):  
G S Drummond ◽  
A Kappas
Keyword(s):  
Single Dose ◽  
Heme Oxygenase ◽  
Competitive Inhibitor ◽  
Bile Pigment ◽  
Human Spleen ◽  
Oxidation Activity ◽  
Heme Oxygenase Activity ◽  
Heme Degradation ◽  
Oxygenase Activity ◽  
Liver And Kidney

The synthetic metalloporphyrin, Cr-protoporphyrin, as a potent competitive inhibitor of heme oxygenase activity in rat spleen, liver, and kidney. When administered to neonatal animals in a single dose immediately after birth, Cr-protoporphyrin suppresses postnatal hyperbilirubinemia and produces a marked and sustained lowering of heme oxidation activity in liver, spleen, and kidney. The metalloporphyrin also potently inhibited the rate of heme degradation to bile pigment in human spleen.

Heme oxygenase activity causes transient hypersensitivity to oxidative ultraviolet a radiation that depends on release of iron from heme

2000 ◽  
Vol 28 (8) ◽  
pp. 1191-1196 ◽  
Author(s):  
Egil Kvam ◽  
Vidya Hejmadi ◽  
Stefan Ryter ◽  
Charareh Pourzand ◽  
Rex M Tyrrell
Keyword(s):  
Heme Oxygenase ◽  
Ultraviolet A ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity

scholarly journals Heme oxygenase activity and hemoglobin neurotoxicity are attenuated by inhibitors of the MEK/ERK pathway

2009 ◽  
Vol 56 (5) ◽  
pp. 922-928 ◽  
Author(s):  
Jing Chen-Roetling ◽  
Zhi Li ◽  
Mai Chen ◽  
Olatilewa O. Awe ◽  
Raymond F. Regan
Keyword(s):  
Heme Oxygenase ◽  
Erk Pathway ◽  
Heme Oxygenase Activity ◽  
Oxygenase Activity
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