Sustained expression of heme oxygenase-1 alters iron homeostasis in nonerythroid cells

Li, Cheng; Lönn, Maria; Xu, Xiangcong; Maghzal, Ghassan J.; Frazer, David M.; Thomas, Shane R.; Halliwell, Barry; Richardson, Des R.; Anderson, Gregory J.; Stocker, Roland

doi:10.1016/j.freeradbiomed.2012.03.007

Cited by 19 publications

(13 citation statements)

References 47 publications

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“…Sufficient data to support or refute such a possibility have not been produced in this study, and the lack of significant HO‐1 induction by the SCSE dosage administered makes any correlations of this kind highly speculative. Moreover, the changes observed in the present study do not fit into a clear pattern that might yield additional in‐depth understanding of SCSE‐mediated alterations in physiologic responses, although some of the results suggest that the extract is affecting iron metabolism at some—which, in turn, might be related to HO‐1 activity based on the known properties of the enzyme (Li et al, ). The most encouraging result of the present study is the absence of any indication of toxicity by subjects consuming the extract.…”

Section: Discussionmentioning

confidence: 99%

Orally Delivered Sour Cherry Seed Extract (SCSE) Affects Cardiovascular and Hematological Parameters in Humans

et al. 2015

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In the present study, we investigated the effects of sour cherry seed extract (SCSE) on a variety of systemic processes that contribute to general health and viability of human subjects. The experiments were conducted according to a double-blind protocol in which six healthy individuals were administered 250-mg/day SCSE for 14 days, while four were treated with placebo. Peripheral blood was collected before and after the treatment period. Samples were analyzed for levels of selected cells, enzymes, or metabolites. Subjects that received SCSE showed increases in the values of mean cell volume, serum transferrin, mean peroxidase index, and representation of peripheral blood lymphocytes. On the other hand, decreases were observed in circulating neutrophils and ferritin levels. Changes observed in the present study do not fit into a clear pattern that might yield additional indepth understanding of SCSE-mediated alterations in physiologic responses. The most encouraging result of the present study is the absence of any indication of toxicity by subjects consuming the extract.

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Section: Discussionmentioning

confidence: 99%

Orally Delivered Sour Cherry Seed Extract (SCSE) Affects Cardiovascular and Hematological Parameters in Humans

et al. 2015

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“…The expression of HO-1 has been shown to be up-regulated in different cancer type [ 14 , 15 , 16 ], but the role it plays in caners has not yet been addressed clearly. Especially, overexpressed or sustained HO-1 alters iron homeostasis in different cell types [ 17 , 18 ]. In this study, we describe that Erastin induces HO-1 expression in HT-1080 fibrosarcoma cells and overexpressed HO-1 accelerates Erastin-triggered ferroptotic cell death.…”

Section: Introductionmentioning

confidence: 99%

Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death

et al. 2015

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The oncogenic RAS-selective lethal small molecule Erastin triggers a unique iron-dependent form of nonapoptotic cell death termed ferroptosis. Ferroptosis is dependent upon the production of intracellular iron-dependent reactive oxygen species (ROS), but not other metals. However, key regulators remain unknown. The heme oxygenase (HO) is a major intracellular source of iron. In this study, the role of heme oxygenase in Erastin-triggered ferroptotic cancer cell death has been investigated. Zinc protoporphyrin IX (ZnPP), a HO-1 inhibitor, prevented Erastin-triggered ferroptotic cancer cell death. Furthermore, Erastin induced the protein and mRNA levels of HO-1 in HT-1080 fibrosarcoma cells. HO-1+/+ and HO-1−/− fibroblast, HO-1 overexpression, and chycloheximide-treated experiments revealed that the expression of HO-1 has a decisive effects in Erastin-triggered cell death. Hemin and CO-releasing molecules (CORM) promote Erastin-induced ferroptotic cell death, not by biliverdin and bilirubin. In addition, hemin and CORM accelerate the HO-1 expression in the presence of Erastin and increase membranous lipid peroxidation. Thus, HO-1 is an essential enzyme for iron-dependent lipid peroxidation during ferroptotic cell death.

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“…Our results showed that expression levels of tricarboxylic acid (TCA) cycle-related molecules, Aco2, malate MDH2 and PDHE-1β, were obviously changed. Of these, Aco2 catalyzes the conversion of citrate to isocitrate via cis -aconitate in the second step of the TCA cycle (43). Aco2 was significantly decreased in the H9c2 cells under cholesterol stimulation.…”

Section: Discussionmentioning

confidence: 99%

HO-1/EBP interaction alleviates cholesterol-induced hypoxia through the activation of the AKT and Nrf2/mTOR pathways and inhibition of carbohydrate metabolism in cardiomyocytes

Jin

Cao

et al. 2017

International Journal of Molecular Medicine

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Heme oxygenase-1 (HO-1) is an inducible and cytoprotective enzyme that provides a defense against oxidant damage. The present study screened 137 HO-1/interacting proteins using a profound co-immunoprecipitation (Co-IP) coupled with proteomics, and profiled the global HO-1 interactome network, including oxidative phosphorylation, endoplasmic reticulum and transport vesicle functions. Among these molecules, we observed that a novel interactor, emopamil-binding protein (EBP), is closely related to the cholesterol metabolism process. This study demonstrated that cholesterol promotes excessive oxidative stress and alters the energy metabolism in cardiomyocytes, further triggering numerous cardiovascular diseases. We observed that cholesterol caused the overexpression of EBP and HO-1 by the activation of AKT and Nrf2/mTOR pathways. In addition, HO-1 and EBP performed a myocardial protective function. The overexpression of HO-1 alleviated the cholesterol-induced excessive oxidative stress status by inhibition of the carbohydrate metabolism. Notably, we also confirmed that the loss of partial HO-1 activity aggravated the oxidative damage and cardiac systolic function induced by a high-fat diet in HO-1 heterozygous (HO-1+/−) mice. These findings indicate that the HO-1/EBP interaction plays a protective role in alleviating the dysfunction of oxidative stress and cardiac systolic function induced by cholesterol stimulation.

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Sustained expression of heme oxygenase-1 alters iron homeostasis in nonerythroid cells

Cited by 19 publications

References 47 publications

Orally Delivered Sour Cherry Seed Extract (SCSE) Affects Cardiovascular and Hematological Parameters in Humans

Orally Delivered Sour Cherry Seed Extract (SCSE) Affects Cardiovascular and Hematological Parameters in Humans

Heme oxygenase-1 accelerates erastin-induced ferroptotic cell death

HO-1/EBP interaction alleviates cholesterol-induced hypoxia through the activation of the AKT and Nrf2/mTOR pathways and inhibition of carbohydrate metabolism in cardiomyocytes

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