Soluble Epoxide Hydrolase Contributes to Cell Senescence and ER Stress in Aging Mice Colon

Wang, Weicang; Wagner, Karen; Wang, Yuxin; Singh, Nalin; Yang, Jun; He, Qiyi; Morisseau, Christophe; Hammock, Bruce D.

doi:10.3390/ijms24054570

Cited by 8 publications

(4 citation statements)

References 51 publications

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“…Smoking, male sex and aging are major risk factors for AAA, and hepatic sEH expression was reported to be positively correlated with age and male sex (26,27). Moreover, smoke exposure has been shown to stimulate lung sEH activity and inflammation in mice (28).…”

Section: Results Seh Expression Is Significantly Higher In the Liver ...mentioning

confidence: 99%

“…Effects of sEH inhibitors on the vasculature are generally presumed to be due to local inhibition of vascular EET metabolism, as EETs that have powerful vasodilatory and anti-inflammatory effects are produced in blood vessels. However, sEH expression is by far highest in the liver compared to other tissues and organs (16,17), and hepatic sEH expression is upregulated with aging, smoking and male sex (24)(25)(26), all of which are important risk factors for AAA.…”

Section: Original Research Articlementioning

confidence: 99%

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Hepatocyte-specific disruption of soluble epoxide hydrolase attenuates abdominal aortic aneurysm formation: novel role of the liver in aneurysm pathogenesis

Kim,

Horimatsu,

Ogbi

et al. 2023

Preprint

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Introduction.Inflammation is a key pathogenic feature of abdominal aortic aneurysm (AAA). Soluble epoxide hydrolase (sEH) is a pro-inflammatory enzyme that converts cytochrome P450-derived epoxides of fatty acids to the corresponding diols, and pharmacological inhibition of sEH prevented AAA formation. Both cytochrome P450 enzymes and sEH are highly expressed in the liver. Here, we investigated the role of hepatic sEH in AAA using a selective pharmacological inhibitor of sEH and hepatocyte-specific Ephx2 (which encodes sEH gene) knockout (KO) mice in two models of AAA [angiotensin II (AngII) infusion and calcium chloride (CaCl2) application].Methods and results.sEH expression and activity were strikingly higher in mouse liver compared with aorta and further increased the context of AAA, in conjunction with elevated expression of the transcription factor Sp1 and the epigenetic regulator Jarid1b, which have been reported to positively regulate sEH expression. Pharmacological sEH inhibition, or liver-specific sEH disruption, achieved by crossing sEH floxed mice with albumin-cre mice, prevented AAA formation in both models, concomitant with reduced expression of hepatic sEH as well as complement factor 3 (C3) and serum amyloid A (SAA), liver-derived factors linked to AAA formation. Moreover, sEH antagonism markedly reduced C3 and SAA protein accumulation in the aortic wall. Co-incubation of liver ex vivo with aneurysm-prone aorta resulted in induction of sEH in the liver, concomitant with upregulation of Sp1, Jarid1b, C3 and SAA gene expression, suggesting that the aneurysm-prone aorta secretes factors that activate sEH and downstream inflammatory signaling in the liver. Using an unbiased proteomic approach, we identified a number of dysregulated proteins [e.g., plastin-2, galectin-3 (gal-3), cathepsin S] released by aneurysm-prone aorta as potential candidate mediators of hepatic sEH induction.Conclusion.We provide the first direct evidence of the liver′s role in orchestrating AAA via the enzyme sEH. These findings not only provide novel insight into AAA pathogenesis, but they have potentially important implications with regard to developing effective medical therapies for AAA.

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Section: Results Seh Expression Is Significantly Higher In the Liver ...mentioning

confidence: 99%

Section: Original Research Articlementioning

confidence: 99%

Hepatocyte-specific disruption of soluble epoxide hydrolase attenuates abdominal aortic aneurysm formation: novel role of the liver in aneurysm pathogenesis

Kim,

Horimatsu,

Ogbi

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

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“…Recently, Wang et al. (2023) established a connection between the chronic exposures of AFB 1 (1500 μg/L in drinking water for 21 days) to Parkinson's disease etiology. In their study, it was reported that continuous AFB 1 oral exposure can induce neuroinflammation, trigger the α‐synuclein pathology, and cause dopaminergic neurotoxicity.…”

Section: Aflatoxin Toxicity and Health Impactmentioning

confidence: 99%

Aflatoxins in food: Prevalence, health effects, and emerging trends in its mitigation—An updated review

Balan,

Dhaulaniya,

Kumar

et al. 2024

Food Safety and Health

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Mycotoxins are secondary metabolites produced by a variety of fungal and mold species. One of the mycotoxin families that is often regarded as the most concerned one in human and animal feeds, is aflatoxin. Aflatoxins produced by Aspergillus species are very toxic and cause significant contamination of food supplies, resulting in serious health repercussions including carcinogenicity. To date, several regulations on aflatoxin permissible level limits have been established in a number of nations. Based on government guidelines and restrictions, consumers and food producers anticipate that aflatoxin contamination in food should not negatively impact human and animal health. Aflatoxin contamination of food commodities poses a consequential risk to humans and is also associated with substantial financial losses. Conventional mycotoxin reduction strategies involve both preventative and decontamination approaches. The present review gives an update on recent research on conventional approaches, including pre‐ and post‐harvest procedures that could potentially be used to decontaminate aflatoxin. Additionally, the current study delves into the source of contamination, global occurrence, impact on human health, and management strategies to assure food security and safety.

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“…48 sEH contributes to cell senescence and ER stress in aging mice. 49 Thus, this study sought to evaluate the functional consequence of sEH overexpression on Ang-II-induced sensitivity by determining the coronary reactive hyperemic (CRH) response by administering exogenous Ang-II in an isolated mouse heart system in vitro. Therefore, we hypothesized the following: (1) AT 1 receptor and CYP4A would be elevated in sEH overexpressed Tie2-sEH Tr compared with their wild-type (WT) counterparts' mouse hearts; (2) sEH overexpression would reduce the CRH response in Tie2-sEH Tr compared with WT mouse hearts; and (3) Ang-II exacerbates CRH-reduction in Tie2-sEH Tr versus Ang-II-treated WT and nontreated Tie2-sEH Tr mouse hearts.…”

Section: Introductionmentioning

confidence: 99%

Overexpression of Human Soluble Epoxide Hydrolase Exacerbates Coronary Reactive Hyperemia Reduction in Angiotensin-II-Treated Mouse Hearts

Hanif,

Edin,

Zeldin

et al. 2024

Journal of Cardiovascular Pharmacology

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Coronary reactive hyperemia (CRH) is impaired in cardiovascular diseases, and angiotensin-II (Ang-II) exacerbates it. However, it is unknown how Ang-II affects CRH in Tie2-sEH Tr (human-sEH-overexpressed) versus wild-type (WT) mice. sEH-overexpression resulted in CRH-reduction in Tie2-sEH Tr versus WT. We hypothesized that Ang-II exacerbates CRH-reduction in Tie2-sEH Tr versus WT. Coronary flow in Tie2-sEH Tr and WT was measured by Langendorff system. The hearts were exposed to 15-second ischemia, and CRH was assessed in 10 mice each. Repayment volume was reduced by 40.50% in WT-treated with Ang-II versus WT (7.42 ± 0.8 to 4.49 ± 0.8 ml/g) and 48% in Tie2-sEH Tr-treated with Ang-II versus Tie2-sEH Tr (5.18 ± 0.4 to 2.68 ± 0.3 ml/g). Ang-II decreased repayment duration by 50% in WT-treated with Ang-II versus WT (2.46 ± 0.5 to 1.24 ± 0.4 min) and 54% in Tie2-sEH Tr-treated with Ang-II versus Tie2-sEH Tr (1.66 ± 0.4 to 0.76 ± 0.2 min). Peak repayment flow was reduced by 11.2% in WT-treated with Ang-II versus WT (35.98 ± 0.7 to 32.11 ± 1.4 ml/g) and 4% in Tie2-sEH Tr-treated with Ang-II versus Tie2-sEH Tr (32.18 ± 0.6 to 30.89 ± 1.5 ml/g). Furthermore, CF was reduced by 43% in WT-treated with Ang-II versus WT (14.2 ± 0.5 to 8.15 ± 0.8 ml/min/g) and 32% in Tie2-sEH Tr-treated with Ang-II versus Tie2-sEH Tr (12.1 ± 0.8 to 8.3 ± 1.2 ml/min/g). Moreover, the Ang-II-AT1-receptor and CYP4A were increased in Tie2-sEHTr. Our results demonstrate that Ang-II exacerbates CRH-reduction in Tie2-sEH Tr mice.

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Soluble Epoxide Hydrolase Contributes to Cell Senescence and ER Stress in Aging Mice Colon

Cited by 8 publications

References 51 publications

Hepatocyte-specific disruption of soluble epoxide hydrolase attenuates abdominal aortic aneurysm formation: novel role of the liver in aneurysm pathogenesis

Hepatocyte-specific disruption of soluble epoxide hydrolase attenuates abdominal aortic aneurysm formation: novel role of the liver in aneurysm pathogenesis

Aflatoxins in food: Prevalence, health effects, and emerging trends in its mitigation—An updated review

Overexpression of Human Soluble Epoxide Hydrolase Exacerbates Coronary Reactive Hyperemia Reduction in Angiotensin-II-Treated Mouse Hearts

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