Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
8.8
7.0
Journals
Antioxidants
Special Issues
Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades
share announcement

Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades

A special issue of Antioxidants (ISSN 2076-3921).

Deadline for manuscript submissions: closed (29 February 2020) | Viewed by 29977

Special Issue Editors

Prof. Dr. Ulrich Göbel

E-Mail Website
Guest Editor
Universitat Freiburg im Breisgau, Department of Anesthesiology and Critical Care Medicine, Freiburg im Breisgau, Germany
Dr. J. Catharina Duvigneau

E-Mail Website
Guest Editor
Department for Biomedical Sciences, Institute for Medical Biochemistry, University of Veterinary Medicine, 1210 Vienna, Austria
Interests: cell culture; qPCR; heme oxygenase activity; sepsis; ischemia/reperfusion; hemorrhagic shock
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Heme oxygenase (HO) is the rate-limiting enzyme in the oxidative degradation of heme, generating biliverdin (BV), carbon monoxide (CO), and iron, while consuming oxygen. Apart from its role as a principal component in the cellular heme/iron homeostasis, HO performs various other cellular processes, which differ among HO families. The function of HO-1 and HO-2, the two catalytically active isoforms of HO in mammals, has been extensively studied. HO-1 and HO-2 appear to act in a synergistic fashion in different tissues, such as kidney, cardiovascular system, and neuronal tissues. HO-1 upregulation has been shown to confer cytoprotection against acute stressful insults in numerous experimental models. Apart from anti-inflammatory, anti-proliferative, and anti-apoptotic activities, the antioxidant properties are gaining increasing attraction. Therefore, the pharmaceutical induction of HO-1 or the application of HO products (e.g., CO) represents a promising therapeutic approach to treating acute and chronic diseases related to oxidative stressors. However, in some models and diseases a prolonged overexpression of HO-1 has been implicated with chronic inflammation, enhanced oxidative stress, and cell injury. Thus, the role of HO in balancing between the beneficial and toxic properties of heme and the heme degradation products appears to be very delicate.

This Special Issue will publish research papers or reviews presenting new findings or concepts on the role of HO and its reaction products in modulating cellular/tissue functions in health and disease. Suitable topics include (but are not limited to) the following: structure and function and regulation of HO and its products, the role of HO and its products in cell metabolism, signalling, cell cycle, epigenetic regulation, repair function, and the control of oxidative stress.

Prof. Dr. Ulrich Göbel
Dr. J. Catharina Duvigneau
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Antioxidants is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 4945 KiB  
Article
Human Heme Oxygenase-1 Induced by Interleukin-6 via JAK/STAT3 Pathways Is a Tumor Suppressor Gene in Hepatoma Cells
by Kun-Chun Chiang, Kang-Shuo Chang, Shu-Yuan Hsu, Hsin-Ching Sung, Tsui-Hsia Feng, Mei Chao and Horng-Heng Juang
Antioxidants 2020, 9(3), 251; https://doi.org/10.3390/antiox9030251 - 19 Mar 2020
Cited by 19 | Viewed by 3927
Abstract
Heme oxygenase-1 (HO-1) has several important roles in hepatocytes in terms of anti-inflammation, anti-apoptosis, and antioxidant properties. Interleukin-6 (IL-6) is a pleiotropic cytokine associated with liver regeneration and protection against injury. The aim of this study was to determine the potential crosstalk between [...] Read more.
Heme oxygenase-1 (HO-1) has several important roles in hepatocytes in terms of anti-inflammation, anti-apoptosis, and antioxidant properties. Interleukin-6 (IL-6) is a pleiotropic cytokine associated with liver regeneration and protection against injury. The aim of this study was to determine the potential crosstalk between HO-1 and IL-6, and to elucidate the signaling pathways involved in the induction of HO-1 by IL-6 in human hepatoma cells. Ectopic overexpression of HO-1 not only attenuated cell proliferation in vitro and in vivo, but also blocked the reactive oxygen species (ROS) induced by H2O2 and the pyocyanin in HepG2 or Hep3B cells. IL-6 expression was negatively regulated by HO-1, while IL-6 induced signal transducer and activator of transcription 3 (STAT3) phosphorylation and HO-1 gene expression in HepG2 cells. The co-transfected HO-1 reporter vector and a protein inhibitor of the activated STAT3 (PIAS3) expression vector blocked the IL-6-induced HO-1 reporter activity. Both interferon γ and interleukin-1β treatments induced STAT1 but not STAT3 phosphorylation, which had no effects on the HO-1 expression. Treatments of AG490 and luteolin blocked the JAK/STAT3 signaling pathways which attenuated IL-6 activation on the HO-1 expression. Our results indicated that HO-1 is the antitumor gene induced by IL-6 through the IL-6/JAK/STAT3 pathways; moreover, a feedback circuit may exist between IL-6 and HO-1 in hepatoma cells. Full article
(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)
►▼ Show Figures

Graphical abstract

24 pages, 3749 KiB  
Article
Cannabidiol Protects Dopaminergic Neurons in Mesencephalic Cultures against the Complex I Inhibitor Rotenone Via Modulation of Heme Oxygenase Activity and Bilirubin
by Johanna Catharina Duvigneau, Alice Trovato, Andrea Müllebner, Ingrid Miller, Christopher Krewenka, Kristina Krenn, Wilhelm Zich and Rudolf Moldzio
Antioxidants 2020, 9(2), 135; https://doi.org/10.3390/antiox9020135 - 04 Feb 2020
Cited by 12 | Viewed by 2926
Abstract
Phytocannabinoids protect neurons against stressful conditions, possibly via the heme oxygenase (HO) system. In cultures of primary mesencephalic neurons and neuroblastoma cells, we determined the capability of cannabidiol (CBD) and tetrahydrocannabinol (THC) to counteract effects elicited by complex I-inhibitor rotenone by analyzing neuron [...] Read more.
Phytocannabinoids protect neurons against stressful conditions, possibly via the heme oxygenase (HO) system. In cultures of primary mesencephalic neurons and neuroblastoma cells, we determined the capability of cannabidiol (CBD) and tetrahydrocannabinol (THC) to counteract effects elicited by complex I-inhibitor rotenone by analyzing neuron viability, morphology, gene expression of IL6, CHOP, XBP1, HO-1 (stress response), and HO-2, and in vitro HO activity. Incubation with rotenone led to a moderate stress response but massive degeneration of dopaminergic neurons (DN) in primary mesencephalic cultures. Both phytocannabinoids inhibited in-vitro HO activity, with CBD being more potent. Inhibition of the enzyme reaction was not restricted to neuronal cells and occurred in a non-competitive manner. Although CBD itself decreased viability of the DNs (from 100 to 78%), in combination with rotenone, it moderately increased survival from 28.6 to 42.4%. When the heme degradation product bilirubin (BR) was added together with CBD, rotenone-mediated degeneration of DN was completely abolished, resulting in approximately the number of DN determined with CBD alone (77.5%). Using N18TG2 neuroblastoma cells, we explored the neuroprotective mechanism underlying the combined action of CBD and BR. CBD triggered the expression of HO-1 and other cell stress markers. Co-treatment with rotenone resulted in the super-induction of HO-1 and an increased in-vitro HO-activity. Co-application of BR completely mitigated the rotenone-induced stress response. Our findings indicate that CBD induces HO-1 and increases the cellular capacity to convert heme when stressful conditions are met. Our data further suggest that CBD via HO may confer full protection against (oxidative) stress when endogenous levels of BR are sufficiently high. Full article
(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)
►▼ Show Figures

Graphical abstract

18 pages, 4103 KiB  
Article
Neuroprotection after Hemorrhagic Stroke Depends on Cerebral Heme Oxygenase-1
by Sandra Kaiser, Sibylle Frase, Lisa Selzner, Judith-Lisa Lieberum, Jakob Wollborn, Wolf-Dirk Niesen, Niels Alexander Foit, Dieter Henrik Heiland and Nils Schallner
Antioxidants 2019, 8(10), 496; https://doi.org/10.3390/antiox8100496 - 19 Oct 2019
Cited by 20 | Viewed by 3886
Abstract
(1) Background: A detailed understanding of the pathophysiology of hemorrhagic stroke is still missing. We hypothesized that expression of heme oxygenase-1 (HO-1) in microglia functions as a protective signaling pathway. (2) Methods: Hippocampal HT22 neuronal cells were exposed to heme-containing blood components and [...] Read more.
(1) Background: A detailed understanding of the pathophysiology of hemorrhagic stroke is still missing. We hypothesized that expression of heme oxygenase-1 (HO-1) in microglia functions as a protective signaling pathway. (2) Methods: Hippocampal HT22 neuronal cells were exposed to heme-containing blood components and cell death was determined. We evaluated HO-1-induction and cytokine release by wildtype compared to tissue-specific HO-1-deficient (LyzM-Cre.Hmox1 fl/fl) primary microglia (PMG). In a study involving 46 patients with subarachnoid hemorrhage (SAH), relative HO-1 mRNA level in the cerebrospinal fluid were correlated with hematoma size and functional outcome. (3) Results: Neuronal cell death was induced by exposure to whole blood and hemoglobin. HO-1 was induced in microglia following blood exposure. Neuronal cells were protected from cell death by microglia cell medium conditioned with blood. This was associated with a HO-1-dependent increase in monocyte chemotactic protein-1 (MCP-1) production. HO-1 mRNA level in the cerebrospinal fluid of SAH-patients correlated positively with hematoma size. High HO-1 mRNA level in relation to hematoma size were associated with improved functional outcome at hospital discharge. (4) Conclusions: Microglial HO-1 induction with endogenous CO production functions as a crucial signaling pathway in blood-induced inflammation, determining microglial MCP-1 production and the extent of neuronal cell death. These results give further insight into the pathophysiology of neuronal damage after SAH and the function of HO-1 in humans. Full article
(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)
►▼ Show Figures

Figure 1

12 pages, 856 KiB  
Article
Spotlight on a New Heme Oxygenase Pathway: Testosterone-Induced Shifts in Cardiac Oxidant/Antioxidant Status
by Renáta Szabó, Denise Börzsei, Krisztina Kupai, Alexandra Hoffmann, Rudolf Gesztelyi, Anikó Magyariné Berkó, Csaba Varga and Anikó Pósa
Antioxidants 2019, 8(8), 288; https://doi.org/10.3390/antiox8080288 - 07 Aug 2019
Cited by 11 | Viewed by 3593
Abstract
A low testosterone level contributes to the development of oxidative damages; however, the cardiovascular effects of exogenous hormone therapy are not well elucidated. The aim of our work is to study the association of the testosterone level, antioxidant/oxidant system, and anti-inflammatory status related [...] Read more.
A low testosterone level contributes to the development of oxidative damages; however, the cardiovascular effects of exogenous hormone therapy are not well elucidated. The aim of our work is to study the association of the testosterone level, antioxidant/oxidant system, and anti-inflammatory status related to the heme oxygenase (HO) system. To determine the effects of testosterone, 10-week-old, and 24-month-old sham-operated and castrated male Wistar rats were used. One part of the castrated animals was daily treated with 2.5 mg/kg cyproterone acetate, while the hormone replacement therapy was performed via an i.m. injection of a dose of 8.0 mg testosterone undecanoate/kg/once a week. The plasma testosterone level, the activity of HO and myeloperoxidase (MPO) enzymes; the concentrations of the HO-1, tumor necrosis alpha (TNF-α), and cyclic guanosine monophosphate (cGMP), as well as the total level of glutathione (GSH + GSSG) were determined from the cardiac left ventricle. In accordance with the testosterone values, the aging process and castration resulted in a decrease in antioxidant HO activity, HO-1 and cGMP concentrations and in the level of GSH + GSSG, whereas the inflammatory TNF-α and MPO activity significantly increased. Testosterone therapy was able to restore the physiological values. Our results clearly show that testosterone replacement therapy increases the antioxidant status and mitigates the inflammatory parameters via the modulation of the HO system. Full article
(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)
►▼ Show Figures

Figure 1

Review

Jump to: Research

26 pages, 1111 KiB  
Review
Role of Heme Oxygenase as a Modulator of Heme-Mediated Pathways
by J. Catharina Duvigneau, Harald Esterbauer and Andrey V. Kozlov
Antioxidants 2019, 8(10), 475; https://doi.org/10.3390/antiox8100475 - 11 Oct 2019
Cited by 62 | Viewed by 7262
Abstract
The heme oxygenase (HO) system is essential for heme and iron homeostasis and necessary for adaptation to cell stress. HO degrades heme to biliverdin (BV), carbon monoxide (CO) and ferrous iron. Although mostly beneficial, the HO reaction can also produce deleterious effects, predominantly [...] Read more.
The heme oxygenase (HO) system is essential for heme and iron homeostasis and necessary for adaptation to cell stress. HO degrades heme to biliverdin (BV), carbon monoxide (CO) and ferrous iron. Although mostly beneficial, the HO reaction can also produce deleterious effects, predominantly attributed to excessive product formation. Underrated so far is, however, that HO may exert effects additionally via modulation of the cellular heme levels. Heme, besides being an often-quoted generator of oxidative stress, plays also an important role as a signaling molecule. Heme controls the anti-oxidative defense, circadian rhythms, activity of ion channels, glucose utilization, erythropoiesis, and macrophage function. This broad spectrum of effects depends on its interaction with proteins ranging from transcription factors to enzymes. In degrading heme, HO has the potential to exert effects also via modulation of heme-mediated pathways. In this review, we will discuss the multitude of pathways regulated by heme to enlarge the view on HO and its role in cell physiology. We will further highlight the contribution of HO to pathophysiology, which results from a dysregulated balance between heme and the degradation products formed by HO. Full article
(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)
►▼ Show Figures

Figure 1

29 pages, 2002 KiB  
Review
The Role of Heme Oxygenase-1 in Remote Ischemic and Anesthetic Organ Conditioning
by Inge Bauer and Annika Raupach
Antioxidants 2019, 8(9), 403; https://doi.org/10.3390/antiox8090403 - 16 Sep 2019
Cited by 11 | Viewed by 3860
Abstract
The cytoprotective effects of the heme oxygenase (HO) pathway are widely acknowledged. These effects are mainly mediated by degradation of free, pro-oxidant heme and the generation of carbon monoxide (CO) and biliverdin. The underlying mechanisms of protection include anti-oxidant, anti-apoptotic, anti-inflammatory and vasodilatory [...] Read more.
The cytoprotective effects of the heme oxygenase (HO) pathway are widely acknowledged. These effects are mainly mediated by degradation of free, pro-oxidant heme and the generation of carbon monoxide (CO) and biliverdin. The underlying mechanisms of protection include anti-oxidant, anti-apoptotic, anti-inflammatory and vasodilatory properties. Upregulation of the inducible isoform HO-1 under stress conditions plays a crucial role in preventing or reducing cell damage. Therefore, modulation of the HO-1 system might provide an efficient strategy for organ protection. Pharmacological agents investigated in the context of organ conditioning include clinically used anesthetics and sedatives. A review from Hoetzel and Schmidt from 2010 nicely summarized the effects of anesthetics on HO-1 expression and their role in disease models. They concluded that HO-1 upregulation by anesthetics might prevent or at least reduce organ injury due to harmful stimuli. Due to its clinical safety, anesthetic conditioning might represent an attractive pharmacological tool for HO-1 modulation in patients. Remote ischemic conditioning (RIC), first described in 1993, represents a similar secure option to induce organ protection, especially in its non-invasive form. The efficacy of RIC has been intensively studied herein, including on patients. Studies on the role of RIC in influencing HO-1 expression to induce organ protection are emerging. In the first part of this review, recently published pre-clinical and clinical studies investigating the effects of anesthetics on HO-1 expression patterns, the underlying signaling pathways mediating modulation and its causative role in organ protection are summarized. The second part of this review sums up the effects of RIC. Full article
(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)
►▼ Show Figures

Figure 1

13 pages, 485 KiB  
Review
Targeting Heme Oxygenase-1 in Cardiovascular and Kidney Disease
by Heather A. Drummond, Zachary L. Mitchell, Nader G. Abraham and David E. Stec
Antioxidants 2019, 8(6), 181; https://doi.org/10.3390/antiox8060181 - 18 Jun 2019
Cited by 20 | Viewed by 3700
Abstract
Heme oxygenase (HO) plays an important role in the cardiovascular system. It is involved in many physiological and pathophysiological processes in all organs of the cardiovascular system. From the regulation of blood pressure and blood flow to the adaptive response to end-organ injury, [...] Read more.
Heme oxygenase (HO) plays an important role in the cardiovascular system. It is involved in many physiological and pathophysiological processes in all organs of the cardiovascular system. From the regulation of blood pressure and blood flow to the adaptive response to end-organ injury, HO plays a critical role in the ability of the cardiovascular system to respond and adapt to changes in homeostasis. There have been great advances in our understanding of the role of HO in the regulation of blood pressure and target organ injury in the last decade. Results from these studies demonstrate that targeting of the HO system could provide novel therapeutic opportunities for the treatment of several cardiovascular and renal diseases. The goal of this review is to highlight the important role of HO in the regulation of cardiovascular and renal function and protection from disease and to highlight areas in which targeting of the HO system needs to be translated to help benefit patient populations. Full article
(This article belongs to the Special Issue Heme Oxygenase-A Balancing Act Between Cytoprotective and Pathophysiological Cascades)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop