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

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.

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Involvement of Heme Oxygenase-1 in Neuropsychiatric and Neurodegenerative Diseases

Current Pharmaceutical Design ◽

10.2174/1381612824666180717160623 ◽

2018 ◽

Vol 24 (20) ◽

pp. 2283-2302 ◽

Cited By ~ 9

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.

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

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/3831750 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 8

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.

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

Current Drug Targets ◽

10.2174/1389450117666160401123600 ◽

2017 ◽

Vol 18 (6) ◽

pp. 674-686 ◽

Cited By ~ 8

Author(s):

Aleksandra Piechota-Polanczyk ◽

Alicja Jozkowicz

Keyword(s):

Cardiovascular Diseases ◽

Heme Oxygenase ◽

Heme Oxygenase 1

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

Laboratory Investigation ◽

10.1038/labinvest.3700205 ◽

2004 ◽

Vol 85 (1) ◽

pp. 34-44 ◽

Cited By ~ 26

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

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

International Journal of Molecular Sciences ◽

10.3390/ijms22158253 ◽

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.

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