Hemin reduces postoperative ileus in a heme oxygenase 1‐dependent manner while dimethyl fumarate does without heme oxygenase 1‐induction

2019 ◽  
Vol 32 (4) ◽  
Author(s):  
Jonas Van Dingenen ◽  
Leen Pieters ◽  
Elien Van Nuffel ◽  
Romain A. Lefebvre
Keyword(s):  
Heme Oxygenase ◽  
Postoperative Ileus ◽  
Dimethyl Fumarate ◽  
Heme Oxygenase 1 ◽  
Dependent Manner

scholarly journals 15-Deoxy-Δ12,14-prostaglandin J2Induces Heme Oxygenase-1 Gene Expression in a Reactive Oxygen Species-dependent Manner in Human Lymphocytes

2004 ◽  
Vol 279 (21) ◽  
pp. 21929-21937 ◽  
Author(s):  
Moisés Álvarez-Maqueda ◽  
Rajaa El Bekay ◽  
Gonzalo Alba ◽  
Javier Monteseirín ◽  
Pedro Chacón ◽  
...  
Keyword(s):  
Gene Expression ◽  
Reactive Oxygen Species ◽  
Heme Oxygenase ◽  
Human Lymphocytes ◽  
Reactive Oxygen ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Oxygen Species

scholarly journals Novel Heme Oxygenase-1 (HO-1) Inducers Based on Dimethyl Fumarate Structure

2020 ◽  
Vol 21 (24) ◽  
pp. 9541
Author(s):  
Valeria Sorrenti ◽  
Luca Vanella ◽  
Chiara Bianca Maria Platania ◽  
Khaled Greish ◽  
Claudio Bucolo ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Stellate Cell ◽  
Binding Free Energy ◽  
Dimethyl Fumarate ◽  
Docking Studies ◽  
Heme Oxygenase 1 ◽  
Expression Data ◽  
Phenyl Rings ◽  
Low Toxicity ◽  
Human Hepatic Stellate Cell

Novel heme oxygenase-1 (HO-1) inducers based on dimethyl fumarate (DMF) structure are reported in this paper. These compounds are obtained by modification of the DMF backbone. Particularly, maintaining the α, β-unsaturated dicarbonyl function as the central chain crucial for HO-1 induction, different substituted or unsubstituted phenyl rings are introduced by means of an ester or amide linkage. Symmetric and asymmetric derivatives are synthesized. All compounds are tested on a human hepatic stellate cell line LX-2 to assay their capacity for modifying HO-1 expression. Compounds 1b, 1l and 1m stand out for their potency as HO-1 inducers, being 2–3 fold more active than DMF, and for their ability to reverse reactive oxygen species (ROS) production mediated using palmitic acid (PA). These properties, coupled with a low toxicity toward LX-2 cell lines, make these compounds potentially useful for treatment of diseases in which HO-1 overexpression may counteract inflammation, such as hepatic fibrosis. Docking studies show a correlation between predicted binding free energy and experimental HO-1 expression data. These preliminary results may support the development of new approaches in the management of liver fibrosis.

Regulation of Heme Oxygenase Expression by Cyclopentenone Prostaglandins

2003 ◽  
Vol 228 (5) ◽  
pp. 499-505 ◽  
Author(s):  
Hean Zhuang ◽  
Sokhon Pin ◽  
Xiaoling Li ◽  
Sylvain Doré
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Heme Oxygenase ◽  
Significant Role ◽  
Neuronal Cell ◽  
Heme Oxygenase 1 ◽  
Neuronal Cultures ◽  
Dependent Manner ◽  
Stress Injury ◽  
Free Radical Damage

Prostaglandins (PGs) originate from the degradation of membranar arachidonic acid by cyclooxygenases (COX-1 and COX-2). The prostaglandin actions in the nervous system are multiple and have been suggested to play a significant role in neurodegenerative disorders. Some PGs have been reported to be toxic and, interestingly, the cyclopentenone PGs have been reported to be cytoprotective at low concentration and could play a significant role in neuronal plasticity. They have been shown to be protective against oxidative stress injury; however, the cellular mechanisms of protection afforded by these PGs are still unclear. It is postulated that the cascade leading to neuronal cell death in acute and chronic neurodegenerative conditions, such as cerebral ischemia and Alzheimer’s disease, would be mediated by free radical damage. We tested the hypothesis that the neuroprotective action of cyclopentanone could be caused partially by an induction of heme oxygenase 1 (HO-1). We and others have previously reported that modulation of HO total activity may well have direct physiological implications in stroke and in Alzheimer’s disease. HO acts as an antioxidant enzyme by degrading heme into iron, carbon monoxide, and biliverdin that is rapidly converted into bilirubin. Using mouse primary neuronal cultures, we demonstrated that PGs of the J series induce HO-1 in a dose-dependent manner (0, 0.5, 5, 10, 20, and 50 μg/ml) and that PGJ2 and dPGJ2 were more potent than PGA2, dPGA2, PGD2, and PGE2. No significant effects were observed for HO-2 and actin expression. In regard to HO-3 expression found in rat, with its protein deducted sequence highly homologous to HO-2, no detection was observed in HO-2−/− mice, suggesting that HO-3 protein would not be present in mouse brain. We are proposing that several of the protective effects of PGJ2 could be mediated through beneficial actions of heme degradation and its metabolites. The design of new mimetics based on the cyclopentenone structure could be very useful as neuroprotective agents and be tested in animal models of stroke and Alzheimer’s disease.

Influence of Heme and Heme Oxygenase-1 Transfection of Pulmonary Microvascular Endothelium on Oxidant Generation and cGMP

2003 ◽  
Vol 228 (5) ◽  
pp. 535-539 ◽  
Author(s):  
Christopher J. Mingone ◽  
Sachin A. Gupte ◽  
Shuo Quan ◽  
Nader G. Abraham ◽  
Michael S. Wolin
Keyword(s):  
Nitric Oxide ◽  
Heme Oxygenase ◽  
Soluble Guanylate Cyclase ◽  
Microvascular Endothelial Cells ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Microvascular Endothelium ◽  
Dichlorofluorescin Diacetate ◽  
Low Serum ◽  
Stimulation Of

Heme is a co-factor required for the stimulation of soluble guanylate cyclase (sGC) by nitric oxide (NO) and carbon monoxide, and sGC activation by these agents is inhibited by superoxide. Because heme promotes oxidant generation, we examined the influence of rat pulmonary microvascular endothelial cells (PMECs) with a stable human heme oxygenase-1 (HO-1) transfection and heme on oxidant generation and cGMP. Culture of PMEC with low serum heme decreased cGMP and the detection of peroxide with 10 μM 2′,7′-dichlorofluorescin diacetate and increased HO-1 further decreased cGMP without altering the peroxide detection under these conditions. Under conditions where heme (30 μM) has been shown to stimulate cGMP production in PMECsby mechanisms involving NO and CO, heme increased the detection of peroxide in a PMEC-dependent manner and HO-1 transfection did not markedly alter the effects heme on peroxide detection. The addition of 1 μM catalase markedly inhibited the effects of heme on peroxide detection whereas increasing (0.1 mM ebselen) or decreasing (depleting glutathione with 7 mM diethylmaleate) rates of intracellular peroxide metabolism or inhibiting the biosynthesis of oxidants (with 10 μM diphenyliodonium or 0.1 mM nitro-L-arginine) had only modest effects. The detection of superoxide by 10 μM dihydroethidium from PMECs was not increased by exposure to heme. These actions of oxidant probes suggest that intracellular oxidants have a minimal influence on the response to heme. Thus, exposure of PMECs to heme causes a complex response involving an extracellular generation of peroxide-derived oxidant species, which do not appear to originate from increases in intracellular superoxide or peroxide. This enables heme and HO to regulate sGC through mechanisms involving NO and CO, which are normally inhibited by superoxide.

scholarly journals Heme Oxygenase-1 Regulates Ferrous Iron and Foxo1 in Control of Hepatic Gluconeogenesis

2021 ◽  
Author(s):  
Ada Admin ◽  
Wang Liao ◽  
Wanbao Yang ◽  
Zheng Shen ◽  
Weiqi Ai ◽  
...  
Keyword(s):  
Iron Overload ◽  
Heme Oxygenase ◽  
Ferrous Iron ◽  
Iron Status ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
Iron Chelator ◽  
Heme Oxygenase 1 ◽  
Dependent Manner

The liver is a key player for maintaining glucose homeostasis. Excessive hepatic glucose production is considered to be a key for the onset of type 2 diabetes mellitus. The primary function of heme oxygenase-1 (HO1) is to catalyze the degradation of heme into biliverdin, ferrous iron, and carbon monoxide. Previous studies have demonstrated that the degradation of heme by HO1 in the liver results in mitochondrial dysfunction and drives insulin resistance. In this study, by overexpressing HO1 in hepatocytes and mice, we showed that HO1 promotes gluconeogenesis in a Foxo1-dependent manner. Importantly, HO1 overexpression increased the generation of ferrous iron in the liver, which further activates NF-<a>κB</a> and phosphorylates Foxo1 at Ser273 to enhance gluconeogenesis. We further assessed the role of HO1 in insulin-resistant L-DKO (liver-specific knockout of IRS1 and IRS2 genes) mice, which exhibit upregulation of HO1 in the liver and hepatic ferrous iron overload. HO1 knockdown by shRNA or treatment of iron chelator rescued the aberrant gluconeogenesis in L-DKO mice. In addition, we found that systemic iron overload promotes gluconeogenesis by activating hepatic PKA→Foxo1 axis. Thus, our results demonstrate the role of HO1 in regulating hepatic iron status and Foxo1 to control gluconeogenesis and blood glucose.

scholarly journals Involvement of Nrf2-Mediated Upregulation of Heme Oxygenase-1 in Mollugin-Induced Growth Inhibition and Apoptosis in Human Oral Cancer Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Young-Man Lee ◽  
Q-Schick Auh ◽  
Deok-Won Lee ◽  
Jun-Yeol Kim ◽  
Ha-Jin Jung ◽  
...  
Keyword(s):  
Cell Death ◽  
Oral Cancer ◽  
Growth Inhibition ◽  
Heme Oxygenase ◽  
Flow Cytometric Analysis ◽  
Annexin V ◽  
Heme Oxygenase 1 ◽  
Related Factor ◽  
Dependent Manner ◽  
Antitumor Effects

Although previous studies have shown that mollugin, a bioactive phytochemical isolated from Rubia cordifolia L. (Rubiaceae), exhibits antitumor effects, its biological activity in oral cancer has not been reported. We thus investigated the effects and putative mechanism of apoptosis induced by mollugin in human oral squamous cell carcinoma cells (OSCCs). Results show that mollugin induces cell death in a dose-dependent manner in primary and metastatic OSCCs. Mollugin-induced cell death involved apoptosis, characterized by the appearance of nuclear shrinkage, flow cytometric analysis of sub-G1 phase arrest, and annexin V-FITC and propidium iodide staining. Western blot analysis and RT-PCR revealed that mollugin suppressed activation of NF-κB and NF-κB-dependent gene products involved in antiapoptosis (Bcl-2 and Bcl-xl), invasion (MMP-9 and ICAM-1), and angiogenesis (FGF-2 and VEGF). Furthermore, mollugin induced the activation of p38, ERK, and JNK and the expression of heme oxygenase-1 (HO-1) and nuclear factor E2–related factor 2 (Nrf2). Mollugin-induced growth inhibition and apoptosis of HO-1 were reversed by an HO-1 inhibitor and Nrf2 siRNA. Collectively, this is the first report to demonstrate the effectiveness of mollugin as a candidate for a chemotherapeutic agent in OSCCs via the upregulation of the HO-1 and Nrf2 pathways and the downregulation of NF-κB.

Overexpression of Heme Oxygenase-1 Promotes Osteoblast Differentiation of Osteoporosis Rat Bone Marrow Stromal Cells in Bone Morphogenetic Protein-Dependent Manner

2019 ◽  
Vol 9 (11) ◽  
pp. 1614-1620
Author(s):  
Jiangrong Fan ◽  
Yong Zheng ◽  
Jingyang You
Keyword(s):  
Cell Proliferation ◽  
Real Time ◽  
Heme Oxygenase ◽  
Real Time Pcr ◽  
Osteoblast Differentiation ◽  
Caspase 3 ◽  
Control Group ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
Alp Activity

BMSCs play a role in osteoporosis (OP) and their differentiation can lead to OP progression. Heme oxygenase-1 (HO-1) involves in many diseases, but the effect of HO-1 on osteoblast differentiation of BMSCs in OP rats remains unclear. SD rats were divided into control group and OP group. Rats BMSCs in OP group were cultured in vitro, HO-1 expression was up-regulated by HO-1 agonist hemin, and BMPR inhibitor LDN-19318 was added followed by analysis of HO-1 expression by real time PCR and ELISA, cell proliferation by MTT assay, apoptosis by Caspase 3 activity, BMP-2 expression by Western blot, ALP activity, expression of Runx2 and OC by real time PCR. In OP group, HO-1 expression was significantly decreased, cell proliferation was inhibited, Caspase 3 activity was increased along with decreased ALP activity and expression of Runx2, OC and BMP-2 compared to control (P < 0.05). Up-regulation of HO-1 expression significantly promoted cell proliferation, reduced Caspase 3 activity, increased ALP activity, and expression of Runx2, OC and BMP-2 (P < 0.05). However, inhibition of HO-1 significantly promoted bone differentiation after the addition of BMPR inhibitor LDN-193189 (P < 0.05). HO-1 expression is decreased in BMSCs of OP group rats. Up-regulation of HO-1 promoted BMSCs proliferation in OP rats in BMP-dependent manner, inhibited apoptosis, and promoted osteoblast differentiation.

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