Heme Oxygenase-1 in Gastrointestinal Tract Health and Disease

Puentes-Pardo, Jose D.; Moreno-SanJuan, Sara; Carazo, Ángel; León, Josefa

doi:10.3390/antiox9121214

Cited by 37 publications

(25 citation statements)

References 206 publications

(285 reference statements)

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“…We next investigated the mechanism by which HO-1 could induce stemness in CRC. As mentioned before, HO-1 could modulate ET-1 production in several models of health and disease [37][38][39][40][41].…”

Section: Ho-1 Overexpression Induces Ece-1 Expression and Et-1 Production By Crc Cellsmentioning

confidence: 69%

“…In the recent years, numerous research works have tried to elucidate the role of HO-1 in colorectal cancer. This has not been an easy task, since this enzyme is found in both cancer and stromal cells, including immune cells [38][39][40][41]. In addition, HO-1 in CRC cells is able to regulate immune-mediated cytotoxicity against CRC cells [18].…”

Section: Discussionmentioning

confidence: 99%

“…We did not test the possible role of ferrous ions on ECE/ET-1 induction by HO-1 overexpression. Similarly to bilirubin, literature to date has shown protective effects of ferrous iron against cancer, mainly due to the induction of ferroptosis and cell death [11,41,64,65].…”

Section: Discussionmentioning

confidence: 99%

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Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53

Ríos‐Arrabal

Puentes-Pardo

Moreno-SanJuan

et al. 2021

JPM

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Heme oxygenase-1 (HO-1) is an antioxidant protein implicated in tumor progression, metastasis, and resistance to therapy. Elevated HO-1 expression is associated with stemness in several types of cancer, although this aspect has not yet been studied in colorectal cancer (CRC). Using an in vitro model, we demonstrated that HO-1 overexpression regulates stemness and resistance to 5-FU treatment, regardless of p53. In samples from CRC patients, HO-1 and endothelin converting enzyme-1 (ECE-1) expression correlated significantly, and p53 had no influence on this result. Carbon monoxide (CO) activated the ECE-1/endothelin-1 (ET-1) pathway, which could account for the protumoral effects of HO-1 in p53 wild-type cells, as demonstrated after treatment with bosentan (an antagonist of both ETRA and ETRB endothelin-1 receptors). Surprisingly, in cells with a non-active p53 or a mutated p53 with gain-of-function, ECE-1-produced ET-1 acted as a protective molecule, since treatment with bosentan led to increased efficiency for spheres formation and percentage of cancer stem cells (CSCs) markers. In these cells, HO-1 could activate or inactivate certain unknown routes that could induce these contrary responses after treatment with bosentan in our cell model. However more research is warranted to confirm these results. Patients carrying tumors with a high expression of both HO-1 and ECE-1 and a non-wild-type p53 should be considered for HO-1 based-therapies instead of ET-1 antagonists-based ones.

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Section: Ho-1 Overexpression Induces Ece-1 Expression and Et-1 Production By Crc Cellsmentioning

confidence: 69%

Section: Discussionmentioning

confidence: 99%

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Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53

Ríos‐Arrabal

Puentes-Pardo

Moreno-SanJuan

et al. 2021

JPM

Self Cite

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“…Literature data confirm the key role of oxidative stress in etiology of numerous and different diseases ( Figure 1 ), including metabolic syndrome [ 6 ], atherosclerosis [ 7 ], cardiovascular disease [ 8 , 9 ], cancer [ 10 , 11 ], neurodegenerative disorders [ 12 , 13 ] diabetes [ 14 ], infertility [ 15 ], renal diseases [ 16 ], and gastrointestinal and hepatic diseases [ 17 ].…”

Section: Introductionmentioning

confidence: 96%

The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

et al. 2021

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Accumulating evidence shows that oxidative stress plays an essential role in the pathogenesis and progression of many diseases. The imbalance between the production of reactive oxygen species (ROS) and the antioxidant systems has been extensively studied in pulmonary, neurodegenerative cardiovascular disorders; however, its contribution is still debated in gastrointestinal disorders. Evidence suggests that oxidative stress affects gastrointestinal motility in obesity, and post-infectious disorders by favoring the smooth muscle phenotypic switch toward a synthetic phenotype. The aim of this review is to gain insight into the role played by oxidative stress in gastrointestinal pathologies (GIT), and the involvement of ROS in the signaling underlying the muscular alterations of the gastrointestinal tract (GIT). In addition, potential therapeutic strategies based on the use of antioxidants for the treatment of inflammatory gastrointestinal diseases are reviewed and discussed. Although substantial progress has been made in identifying new techniques capable of assessing the presence of oxidative stress in humans, the biochemical-molecular mechanisms underlying GIT mucosal disorders are not yet well defined. Therefore, further studies are needed to clarify the mechanisms through which oxidative stress-related signaling can contribute to the alteration of the GIT mucosa in order to devise effective preventive and curative therapeutic strategies

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“…Heme oxygenase (HO) is an enzyme that catalyzes heme degradation to generate biliverdin, free iron, and carbon monoxide [ 12 ]. To date, two main isoforms of this enzyme—HO-1 and HO-2—have been identified.…”

Section: Introductionmentioning

confidence: 99%

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

Kim

Choi

Leem

et al. 2021

IJMS

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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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Heme Oxygenase-1 in Gastrointestinal Tract Health and Disease

Cited by 37 publications

References 206 publications

Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53

Endothelin-1 as a Mediator of Heme Oxygenase-1-Induced Stemness in Colorectal Cancer: Influence of p53

The Impact of Oxidative Stress in Human Pathology: Focus on Gastrointestinal Disorders

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

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