Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

2018 ◽  
Vol 24 (20) ◽  
pp. 2283-2302 ◽  
Author(s):  
Vivian B. Neis ◽  
Priscila B. Rosa ◽  
Morgana Moretti ◽  
Ana Lucia S. Rodrigues
Keyword(s):  
Neurodegenerative Diseases ◽  
Heme Oxygenase ◽  
Therapeutic Potential ◽  
Redox Homeostasis ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Physiological Conditions ◽  
And Oxidative Stress ◽  
Defensive Mechanism

Heme oxygenase (HO) family catalyzes the conversion of heme into free iron, carbon monoxide and biliverdin. It possesses two well-characterized isoforms: HO-1 and HO-2. Under brain physiological conditions, the expression of HO-2 is constitutive, abundant and ubiquitous, whereas HO-1 mRNA and protein are restricted to small populations of neurons and neuroglia. HO-1 is an inducible enzyme that has been shown to participate as an essential defensive mechanism for neurons exposed to oxidant challenges, being related to antioxidant defenses in certain neuropathological conditions. Considering that neurodegenerative diseases (Alzheimer’s Disease (AD), Parkinson’s Disease (PD) and Multiple Sclerosis (MS)) and neuropsychiatric disorders (depression, anxiety, Bipolar Disorder (BD) and schizophrenia) are associated with increased inflammatory markers, impaired redox homeostasis and oxidative stress, conditions that may be associated with alterations in HO-levels/activity, the purpose of this review is to present evidence on the possible role of HO-1 in these Central Nervous System (CNS) diseases. In addition, the possible therapeutic potential of targeting brain HO-1 is explored in this review.

scholarly journals The Effect of Heme Oxygenase on Ganglioside Redistribution Within Hepatocytes in Experimental Estrogen-Induced Cholestasis

2014 ◽  
pp. 359-367
Author(s):  
T. PETR ◽  
V. ŠMÍD ◽  
V. KUČEROVÁ ◽  
K. VÁŇOVÁ ◽  
M. LENÍČEK ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Antioxidant Defenses ◽  
Heme Oxygenase 1 ◽  
Cholestatic Liver Disease ◽  
Therapeutic Measure ◽  
Liver Homogenates ◽  
Total Bile Acids ◽  
And Oxidative Stress ◽  
Oxidative Effect

Cholestasis is characterized by the elevation of serum total bile acids (TBA), which leads to the production of both free radicals and oxidative stress. Although they do not share the same mechanisms, membrane glycosphingolipids (GSL) and the antioxidant enzyme heme oxygenase-1 (HMOX1) both act against the pro-oxidative effect of TBA. The aim of the study was to assess the role of HMOX on GSL redistribution and composition within hepatocytes in the rat model of estrogen-induced cholestasis. Compared to the controls, an increase of total gangliosides in the liver homogenates of the cholestatic group (P=0.001) was detected; further, it paralleled along with the activation of their biosynthetic b-branch pathway (P<0.01). These effects were partially prevented by HMOX activation. Cholestasis was accompanied by a redistribution of GM1 ganglioside from the cytoplasm to the sinusoids; while HMOX activation led to the retention of GM1 in the cytoplasm (P=0.014). Our study shows that estrogen-induced cholestasis is followed by changes in the synthesis and/or distribution of GSL. These changes are not only triggered by the detergent power of accumulated TBA, but also by their pro-oxidant action. Increases in the antioxidant defenses might represent an important supportive therapeutic measure for patients with cholestatic liver disease.

scholarly journals NUPR1: A Critical Regulator of the Antioxidant System

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3670
Author(s):  
Can Huang ◽  
Patricia Santofimia-Castaño ◽  
Juan Iovanna
Keyword(s):  
Oxidative Stress ◽  
Antioxidant System ◽  
Mitochondrial Function ◽  
Therapeutic Potential ◽  
Current Knowledge ◽  
Redox Homeostasis ◽  
Antioxidant Genes ◽  
Intrinsically Disordered ◽  
And Oxidative Stress

Nuclear protein 1 (NUPR1) is a small intrinsically disordered protein (IDP) activated in response to various types of cellular stress, including endoplasmic reticulum (ER) stress and oxidative stress. Reactive oxygen species (ROS) are mainly produced during mitochondrial oxidative metabolism, and directly impact redox homeostasis and oxidative stress. Ferroptosis is a ROS-dependent programmed cell death driven by an iron-mediated redox reaction. Substantial evidence supports a maintenance role of the stress-inducible protein NUPR1 on cancer cell metabolism that confers chemotherapeutic resistance by upregulating mitochondrial function-associated genes and various antioxidant genes in cancer cells. NUPR1, identified as an antagonist of ferroptosis, plays an important role in redox reactions. This review summarizes the current knowledge on the mechanism behind the observed impact of NUPR1 on mitochondrial function, energy metabolism, iron metabolism, and the antioxidant system. The therapeutic potential of genetic or pharmacological inhibition of NUPR1 in cancer is also discussed. Understanding the role of NUPR1 in the antioxidant system and the mechanisms behind its regulation of ferroptosis may promote the development of more efficacious strategies for cancer therapy.

scholarly journals Heme Oxygenase-1 Signaling and Redox Homeostasis in Physiopathological Conditions

Biomolecules ◽  
2021 ◽  
Vol 11 (4) ◽  
pp. 589
Author(s):  
Valeria Consoli ◽  
Valeria Sorrenti ◽  
Salvo Grosso ◽  
Luca Vanella
Keyword(s):  
Carbon Monoxide ◽  
Heme Oxygenase ◽  
Redox Homeostasis ◽  
Transformation Products ◽  
Antioxidant Response ◽  
Heme Oxygenase 1 ◽  
Ferrous Ions ◽  
Biliverdin Reductase ◽  
Rate Limiting Step

Heme-oxygenase is the enzyme responsible for degradation of endogenous iron protoporphyirin heme; it catalyzes the reaction’s rate-limiting step, resulting in the release of carbon monoxide (CO), ferrous ions, and biliverdin (BV), which is successively reduced in bilirubin (BR) by biliverdin reductase. Several studies have drawn attention to the controversial role of HO-1, the enzyme inducible isoform, pointing out its implications in cancer and other diseases development, but also underlining the importance of its antioxidant activity. The contribution of HO-1 in redox homeostasis leads to a relevant decrease in cells oxidative damage, which can be reconducted to its cytoprotective effects explicated alongside other endogenous mechanisms involving genes like TIGAR (TP53-induced glycolysis and apoptosis regulator), but also to the therapeutic functions of heme main transformation products, especially carbon monoxide (CO), which has been shown to be effective on GSH levels implementation sustaining body’s antioxidant response to oxidative stress. The aim of this review was to collect most of the knowledge on HO-1 from literature, analyzing different perspectives to try and put forward a hypothesis on revealing yet unknown HO-1-involved pathways that could be useful to promote development of new therapeutical strategies, and lay the foundation for further investigation to fully understand this important antioxidant system.

scholarly journals Astrocyte-Neuron Metabolic Crosstalk in Neurodegeneration: A Mitochondrial Perspective

2021 ◽  
Vol 12 ◽  
Author(s):  
Patrycja Mulica ◽  
Anne Grünewald ◽  
Sandro L. Pereira
Keyword(s):  
Neurodegenerative Diseases ◽  
Mitochondrial Dysfunction ◽  
Therapeutic Potential ◽  
Special Focus ◽  
Neuronal Function ◽  
Supportive Role ◽  
The Brain ◽  
And Oxidative Stress ◽  
Brain Energetics

Converging evidence made clear that declining brain energetics contribute to aging and are implicated in the initiation and progression of neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. Indeed, both pathologies involve instances of hypometabolism of glucose and oxygen in the brain causing mitochondrial dysfunction, energetic failure and oxidative stress. Importantly, recent evidence suggests that astrocytes, which play a key role in supporting neuronal function and metabolism, might contribute to the development of neurodegenerative diseases. Therefore, exploring how the neuro-supportive role of astrocytes may be impaired in the context of these disorders has great therapeutic potential. In the following, we will discuss some of the so far identified features underlining the astrocyte-neuron metabolic crosstalk. Thereby, special focus will be given to the role of mitochondria. Furthermore, we will report on recent advancements concerning iPSC-derived models used to unravel the metabolic contribution of astrocytes to neuronal demise. Finally, we discuss how mitochondrial dysfunction in astrocytes could contribute to inflammatory signaling in neurodegenerative diseases.

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 Red Yeast Rice Protects Circulating Bone Marrow-Derived Proangiogenic Cells against High-Glucose-Induced Senescence and Oxidative Stress: The Role of Heme Oxygenase-1

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Jung-Tung Liu ◽  
Huey-Yi Chen ◽  
Wen-Chi Chen ◽  
Kee-Ming Man ◽  
Yung-Hsiang Chen
Keyword(s):  
Oxidative Stress ◽  
Bone Marrow ◽  
Heme Oxygenase ◽  
High Glucose ◽  
Protoporphyrin Ix ◽  
Vascular Complications ◽  
Heme Oxygenase 1 ◽  
Red Yeast Rice ◽  
And Oxidative Stress

The inflammation and oxidative stress of bone marrow-derived proangiogenic cells (PACs), also named endothelial progenitor cells, triggered by hyperglycemia contributes significantly to vascular dysfunction. There is supporting evidence that the consumption of red yeast rice (RYR; Monascus purpureus-fermented rice) reduces the vascular complications of diabetes; however, the underlying mechanism remains unclear. This study aimed to elucidate the effects of RYR extract in PACs, focusing particularly on the role of a potent antioxidative enzyme, heme oxygenase-1 (HO-1). We found that treatment with RYR extract induced nuclear factor erythroid-2-related factor nuclear translocation and HO-1 mRNA and protein levels in PACs. RYR extract inhibited high-glucose-induced (30 mM) PAC senescence and the development of reactive oxygen species (ROS) in a dose-dependent manner. The HO-1 inducer cobalt protoporphyrin IX also decreased high-glucose-induced cell senescence and oxidative stress, whereas the HO-1 enzyme inhibitor zinc protoporphyrin IX and HO-1 small interfering RNA significantly reversed RYR extract-caused inhibition of senescence and reduction of oxidative stress in high-glucose-treated PACs. These results suggest that RYR extract serves as alternative and complementary medicine in the treatment of these diseases, by inducing HO-1, thereby decreasing the vascular complications of diabetes.

The Role of Statins in the Activation of Heme Oxygenase-1 in Cardiovascular Diseases

2017 ◽  
Vol 18 (6) ◽  
pp. 674-686 ◽  
Author(s):  
Aleksandra Piechota-Polanczyk ◽  
Alicja Jozkowicz
Keyword(s):  
Cardiovascular Diseases ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

scholarly journals Potential role of heme oxygenase-1 in the progression of rat adjuvant arthritis

2004 ◽  
Vol 85 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Isabel Devesa ◽  
Maria Luisa Ferrándiz ◽  
Isabel Guillén ◽  
José Miguel Cerdá ◽  
Maria José Alcaraz
Keyword(s):  
Heme Oxygenase ◽  
Adjuvant Arthritis ◽  
Potential Role ◽  
Heme Oxygenase 1 ◽  
Rat Adjuvant Arthritis

scholarly journals Pharmacological Targeting of Heme Oxygenase-1 in Osteoarthritis

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 419
Author(s):  
Yohei Sanada ◽  
Sho Joseph Ozaki Tan ◽  
Nobuo Adachi ◽  
Shigeru Miyaki
Keyword(s):  
Heme Oxygenase ◽  
Redox Homeostasis ◽  
Synovial Fibroblasts ◽  
Protective Role ◽  
Joint Disease ◽  
Heme Oxygenase 1 ◽  
Transcriptional Level ◽  
Related Factor ◽  
Mobility Limitations ◽  
Therapeutic Implications

Osteoarthritis (OA) is a common aging-associated disease that clinically manifests as joint pain, mobility limitations, and compromised quality of life. Today, OA treatment is limited to pain management and joint arthroplasty at the later stages of disease progression. OA pathogenesis is predominantly mediated by oxidative damage to joint cartilage extracellular matrix and local cells such as chondrocytes, osteoclasts, osteoblasts, and synovial fibroblasts. Under normal conditions, cells prevent the accumulation of reactive oxygen species (ROS) under oxidatively stressful conditions through their adaptive cytoprotective mechanisms. Heme oxygenase-1 (HO-1) is an iron-dependent cytoprotective enzyme that functions as the inducible form of HO. HO-1 and its metabolites carbon monoxide and biliverdin contribute towards the maintenance of redox homeostasis. HO-1 expression is primarily regulated at the transcriptional level through transcriptional factor nuclear factor erythroid 2 (NF-E2)-related factor 2 (Nrf2), specificity protein 1 (Sp1), transcriptional repressor BTB-and-CNC homology 1 (Bach1), and epigenetic regulation. Several studies report that HO-1 expression can be regulated using various antioxidative factors and chemical compounds, suggesting therapeutic implications in OA pathogenesis as well as in the wider context of joint disease. Here, we review the protective role of HO-1 in OA with a focus on the regulatory mechanisms that mediate HO-1 activity.

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