scholarly journals Reciprocal Effects of Oxidative Stress on Heme Oxygenase Expression and Activity Contributes to Reno-Vascular Abnormalities in EC-SOD Knockout Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-11 ◽  
Author(s):  
Tomoko Kawakami ◽  
Nitin Puri ◽  
Komal Sodhi ◽  
Lars Bellner ◽  
Toru Takahashi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Redox Homeostasis ◽  
Inhibitory Effect ◽  
Serum Adiponectin ◽  
Causative Role ◽  
Vascular Abnormalities ◽  
Chronic Oxidative Stress ◽  
Cobalt Protoporphyrin ◽  
Physiological Abnormalities

Heme oxygenase (HO) system is one of the key regulators of cellular redox homeostasis which responds to oxidative stress (ROS) via HO-1 induction. However, recent reports have suggested an inhibitory effect of ROS on HO activity. In light of these conflicting reports, this study was designed to evaluate effects of chronic oxidative stress on HO system and its role in contributing towards patho-physiological abnormalities observed in extracellular superoxide dismutase (EC-SOD, SOD3) KO animals. Experiments were performed in WT and EC-SOD(−/−)mice treated with and without HO inducer, cobalt protoporphyrin (CoPP). EC-SOD(−/−)mice exhibited oxidative stress, renal histopathological abnormalities, elevated blood pressure, impaired endothelial function, reduced p-eNOS, p-AKT and increased HO-1 expression; although, HO activity was significantly (P<0.05) attenuated along with attenuation of serum adiponectin and vascular epoxide levels (P<0.05). CoPP, in EC-SOD(−/−)mice, enhanced HO activity (P<0.05) and reversed aforementioned pathophysiological abnormalities along with restoration of vascular EET, p-eNOS, p-AKT and serum adiponectin levels in these animals. Taken together our results implicate a causative role of insufficient activation of heme-HO-adiponectin system in pathophysiological abnormalities observed in animal models of chronic oxidative stress such as EC-SOD(−/−)mice.

scholarly journals Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model

2021 ◽  
Vol 22 (15) ◽  
pp. 8253
Author(s):  
Jung-Yeon Kim ◽  
Yongmin Choi ◽  
Jaechan Leem ◽  
Jeong Eun Song
Keyword(s):  
Oxidative Stress ◽  
Liver Disease ◽  
Heme Oxygenase ◽  
Murine Model ◽  
Liver Diseases ◽  
Transforming Growth Factor ◽  
Heme Oxygenase 1 ◽  
Cholestatic Liver Disease ◽  
Hepatocyte Apoptosis ◽  
Cobalt Protoporphyrin

Cholestatic liver diseases can progress to end-stage liver disease and reduce patients’ quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-β pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.

scholarly journals Antioxidant Roles of Heme Oxygenase, Carbon Monoxide, and Bilirubin in Cerebral Circulation during Seizures

2012 ◽  
Vol 32 (6) ◽  
pp. 1024-1034 ◽  
Author(s):  
Helena Parfenova ◽  
Charles W Leffler ◽  
Shyamali Basuroy ◽  
Jianxiong Liu ◽  
Alexander L Fedinec
Keyword(s):  
Oxidative Stress ◽  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Vascular Dysfunction ◽  
Antioxidant Properties ◽  
Cerebrovascular Function ◽  
Cerebrovascular Dysfunction ◽  
Cobalt Protoporphyrin ◽  
Endogenous Antioxidant ◽  
The Brain

Postictal cerebrovascular dysfunction is an adverse effect of seizures in newborn piglets. The brain heme oxygenase (HO) provides protection against cerebrovascular dysfunction. We investigated the contribution of reactive oxygen species (ROS) to seizure-induced vascular damage and the mechanism of HO vasoprotection. In a bicuculline model of seizures, we addressed the hypotheses: (1) seizures increase brain ROS; (2) ROS contribute to cerebral vascular dysfunction; (3) ROS initiate a vasoprotective mechanisms by activating endogenous HO; and (4) HO products have antioxidant properties. As assessed by dihydroethidium oxidation (ox-DHE), seizures increased ROS in cerebral vessels and cortical astrocytes; ox-DHE elevation was prevented by tiron and apocynin. An HO inhibitor, tin protoporphyrin, potentiated, whereas an HO-1 inducer, cobalt protoporphyrin, blocked seizure-induced increase in DHE oxidation. Heme oxygenase products carbon monoxide (CO) (CORM-A1) and bilirubin attenuated ox-DHE elevation during seizures. Antioxidants tiron and bilirubin prevented the loss of postictal cerebrovascular dilations to bradykinin, glutamate, and sodium nitroprusside. Tiron and apocynin abrogated activation of the brain HO during seizures. Overall, these data suggest that long-term adverse cerebrovascular effects of seizures are attributed to oxidative stress. On the other hand, seizure-induced ROS are required for activation of the endogenous antioxidant HO/CO/bilirubin system that alleviates oxidative stress-induced loss of postictal cerebrovascular function in piglets.

Abstract P338: Heme Oxygenase Induction Suppresses Hepatic Hepcidin and Rescues Ferroportin and Ferritin Expression in Obese Mice

Hypertension ◽  
2016 ◽  
Vol 68 (suppl_1) ◽  
Author(s):  
Hibba Chaudhry ◽  
Alexandra Nichols ◽  
Komal Sodhi ◽  
Krithika Srikanthan ◽  
Athar Nawab
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Iron Homeostasis ◽  
Transmembrane Protein ◽  
Low Grade ◽  
Obese Mice ◽  
Liver Iron ◽  
Cellular Iron ◽  
Cobalt Protoporphyrin ◽  
Stress Response System

Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron levels by increasing internalization of ferroportin- a transmembrane protein facilitating egress of cellular iron. Chronic low-grade inflammatory states, such as obesity, have been shown to increase oxidative stress and enhance hepcidin secretion from hepatocytes and macrophages. Heme-heme oxygenase (HO) is a stress response system, the induction of which reduces oxidative stress thereby abating patho-physiological conditions such as obesity and metabolic syndrome.8 week old male obese (ob) mice and their age- and sex-matched lean mice were used as controls. CoPP was administered intraperitoneally once a week (3 mg/kg) for 6 weeks to obese mice. CoPP plus stannous mesoporphyrin (SnMP) was administered intraperitoneally three times a week (20 mg/kg) for 6 weeks. We investigated the effects of HO-1 induction on hepatic hepcidin levels and on iron homeostasis in tissues from lean and obese mice. Obese mice exhibited hyperglycemia along with increased levels of pro-inflammatory cytokines (MCP-1, IL-6, p<0.05), oxidative stress and increased hepatic hepcidin levels (p<0.05). Enhancement of hepcidin was reflected in the reduced expression of ferroportin in obese mice (p<0.05). Further, our results showed attenuation of insulin receptor phosphorylation and attenuation of metabolic regulators including pAMPK, pAKT and pLKB1. Cobalt protoporphyrin (CoPP)-induced HO-1 up-regulation in obese mice and reversed these pathophysiological alterations (p<0.05) while attenuating hepatic hepcidin levels and enhancing ferritin expression. These effects of CoPP were prevented in obese mice concurrently exposed to an inhibitor of HO (SnMP) (p<0.05). Taken together, our results highlight a modulatory effect of HO on iron homeostasis mediated through the suppression of hepatic hepcidin in conjunction with the rescue of cellular ferritin levels. Therefore, these findings may prove an effective strategy in treating the metabolic consequences of obesity including alteration of liver iron homeostasis.

scholarly journals Role of ATM in Oxidative Stress-mediated c-Jun Phosphorylation in Response to Ionizing Radiation and CdCl2

2001 ◽  
Vol 276 (15) ◽  
pp. 11783-11790 ◽  
Author(s):  
Sung A. Lee ◽  
Anatoly Dritschilo ◽  
Mira Jung
Keyword(s):  
Oxidative Stress ◽  
Ionizing Radiation ◽  
Heme Oxygenase ◽  
Redox Homeostasis ◽  
Heme Oxygenase 1 ◽  
Second Phase ◽  
Radiation Induced ◽  
Factor C ◽  
And Control

Ionizing radiation-induced phosphorylation of the transcription factor c-Jun is impaired in cells derived from individuals with ataxia telangiectasia (AT), in which theATMgene is mutated. We demonstrate here that ATM modulates c-Jun phosphorylation following exposure to ionizing radiation as well as treatment with CdCl2, a potent pro-oxidant. Exposure of AT and control fibroblasts to CdCl2induced a biphasic increase in c-Jun phosphorylation on serine residues 63 and 73, with the extent of the second phase being markedly greater in AT cells than in control cells. Heme oxygenase-1, a marker of oxidative stress, was also significantly induced in AT fibroblasts. Expression of recombinant ATM in AT fibroblasts, however, reduced the extent of the effects of CdCl2on both c-Jun phosphorylation and heme oxygenase-1 induction. Our data suggest that ATM contributes to oxidative stress-mediated signaling that leads to c-Jun phosphorylation by acting as a sensor of ionizing radiation-induced oxidative stress and by modulating intracellular redox homeostasis.

scholarly journals Inhibition of JNK Alleviates Chronic Hypoperfusion-Related Ischemia Induces Oxidative Stress and Brain Degeneration via Nrf2/HO-1 and NF-κB Signaling

2020 ◽  
Vol 2020 ◽  
pp. 1-18
Author(s):  
Muhammad Sohail Khan ◽  
Amjad Khan ◽  
Sareer Ahmad ◽  
Riaz Ahmad ◽  
Inayat U. R. Rehman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cerebral Ischemia ◽  
Inhibitory Effect ◽  
Ischemic Brain Injury ◽  
Ischemic Brain ◽  
Adult Mice ◽  
Chronic Oxidative Stress ◽  
Long Time ◽  
Brain Degeneration

Cerebral ischemia is one of the leading causes of neurological disorders. The exact molecular mechanism related to chronic unilateral cerebral ischemia-induced neurodegeneration and memory deficit has not been precisely elucidated. In this study, we examined the effect of chronic ischemia on the induction of oxidative stress and c-Jun N-terminal kinase-associated detrimental effects and unveiled the inhibitory effect of specific JNK inhibitor (SP600125) on JNK-mediated brain degeneration in adult mice. Our behavioral, biochemical, and immunofluorescence studies revealed that chronic ischemic injuries sustained increased levels of oxidative stress-induced active JNK for a long time, whereas SP600125 significantly reduced the elevated level of active JNK and further regulated Nrf2/HO-1 and NF-κB signaling, which have been confirmed in vivo. Neuroinflammatory mediators and loss of neuronal cells was significantly reduced with the administration of SP600125. Ischemic brain injury caused synaptic dysfunction and memory impairment in mice. However, these were significantly improved with SP600125. On the whole, these findings suggest that elevated ROS-mediated JNK is a key mediator in chronic ischemic conditions and has a crucial role in neuroinflammation, neurodegeneration, and memory dysfunction. Our findings suggest that chronic oxidative stress associated JNK would be a potential target in time-dependent studies of chronic ischemic conditions induced brain degeneration.

scholarly journals Heme Oxygenase Induction Suppresses Hepatic Hepcidin and Rescues Ferroportin and Ferritin Expression in Obese Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Nitin Puri ◽  
Yevgeniy Arefiev ◽  
Robert Chao ◽  
David Sacerdoti ◽  
Hibba Chaudry ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Iron Homeostasis ◽  
Transmembrane Protein ◽  
Low Grade ◽  
Obese Mice ◽  
Cellular Iron ◽  
Cobalt Protoporphyrin ◽  
Stress Response System ◽  
Metabolic Regulators

Hepcidin, a phase II reactant secreted by hepatocytes, regulates cellular iron levels by increasing internalization of ferroportin-a transmembrane protein facilitating egress of cellular iron. Chronic low-grade inflammatory states, such as obesity, have been shown to increase oxidative stress and enhance hepcidin secretion from hepatocytes and macrophages. Heme-heme oxygenase (HO) is a stress response system which reduces oxidative stress. We investigated the effects of HO-1 induction on hepatic hepcidin levels and on iron homeostasis in hepatic tissues from lean and obese mice. Obese mice exhibited hyperglycemia (p<0.05); increased levels of proinflammatory cytokines (MCP-1, IL-6,p<0.05); oxidative stress (p<0.05); and increased hepatic hepcidin levels (p<0.05). Enhancement of hepcidin was reflected in the reduced expression of ferroportin in obese mice (p<0.05). However, this effect is accompanied by a significant decline in ferritin expression. Additionally, there are reduced insulin receptor phosphorylation and attenuation of metabolic regulators pAMPK, pAKT, and pLKB1. Cobalt protoporphyrin- (CoPP-) induced HO-1 upregulation in obese mice reversed these alterations (p<0.05), while attenuating hepatic hepcidin levels. These effects of CoPP were prevented in obese mice concurrently exposed to an inhibitor of HO (SnMP) (p<0.05). Our results highlight a modulatory effect of HO on iron homeostasis mediated through the suppression of hepatic hepcidin.

Pharmacological study on the possible involvement of a Nrf2 -Heme oxygenase pathways in anti-cataract activity of fisetin

2020 ◽  
Vol 10 (1) ◽  
pp. 14-19
Author(s):  
Krishna Reddy BV ◽  
Avinash Kumar Reddy G ◽  
Sujitha V ◽  
Manasa A
Keyword(s):  
Oxidative Stress ◽  
Heme Oxygenase ◽  
Pharmacological Study ◽  
World Population ◽  
Central Feature ◽  
Beneficial Effects ◽  
Radical Production ◽  
Anti Oxidant ◽  
Diabetic Population ◽  
Oxidant Status

DM otherwise diabetes is now a days an epidemic with the percentage of patient population rising to almost 10% of the world population. Out of all the DM complications, cataract leads the way contributing to disabilities to about 60% of diabetic population. But the pathogenesis of DM cataract is still a half-understood area of medicine there by posing a problem in the therapy. The data that we have till now gives us enough evidence to advocate the oxidative stress has a major role for the pathogenesis of DM complications like DMnephropathy, DMneuropathy, and cardiac hypertrophy, which suggests the oxidative stress is a central feature of diabetes. In the current research, the pharmacological evaluation of Fisetin for its DM based anti-cataract property was performed. This research concentrates to estimate the possible involvement of Nrf-2 / heme oxygenase (HO)-pathway in the observed therapeutic effect, if any. The data obtained in this study also indicate that the observed beneficial effects mainly due to activation of Nrf2/HO-1 pathway. These effects probably result in increased tissue anti-oxidant status as well as decreased free radical production, which ultimately responsible for the observed beneficial effects of Fisetin against hyperglycemia-induced cataract.

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