Inhibition of homocysteine-induced endoplasmic reticulum stress and endothelial cell damage by l-serine and glycine

Sim, Woo-Cheol; Han, Inhoi; Lee, Wonseok; Choi, Youngseok; Lee, Kang-Yo; Kim, Dong Gwang; Jung, Sung Il; Oh, Seon-Hee; Lee, Byung‐Hoon

doi:10.1016/j.tiv.2016.04.004

Cited by 20 publications

(8 citation statements)

References 28 publications

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“…In our recent study, suckling-piglets receiving glycine presented an improvement in intestinal mucosal barrier function and a repression of ER stress-related apoptosis in jejunal epithelial cells during the postweaning period ( Fan et al., 2019 ). This finding is consistent with a previous report ( Sim et al., 2016 ), indicating a regulatory effect of glycine on ER stress. However, the underlying mechanism responsible for the effect of glycine on ER stress has not been fully defined.…”

Section: Introductionsupporting

confidence: 94%

Glycine represses endoplasmic reticulum stress-related apoptosis and improves intestinal barrier by activating mammalian target of rapamycin complex 1 signaling

Yang

Fan

et al. 2022

Animal Nutrition

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Endoplasmic reticulum (ER) stress has been associated with the dysfunction of intestinal barrier in humans and animals. We have previously shown that oral administration of glycine to suckling-piglets improves ER stress-related intestinal mucosal barrier impairment and jejunal epithelial apoptosis. However, the underlying mechanism remains unknown. In this study, the protective effect and the mechanism of glycine on apoptosis and dysfunction in intestinal barrier induced by brefeldin A (BFA), an ER stress inducer, was explored in porcine intestinal epithelial cells (IPEC-1). The results showed that BFA treatment led to enhanced apoptosis and upregulation of proteins involved in ER stress signaling, including inositol-requiring enzyme 1α (IRE1α), activating transcription factor 6α (ATF6α), c-Jun N-terminal kinase (JNK), and C/EBP-homologous protein (CHOP). In addition, BFA induced a dysfunction in intestinal epithelial barrier, as evidenced by the increased paracellular permeability, decreased transepithelial electrical resistance (TEER), and reduced abundance of tight junction proteins (occludin, claudin-1, zonula occludens [ZO]-1, and ZO-2). These alterations triggered by BFA were significantly abolished by glycine treatment ( P < 0.05), indicating a protective effect of glycine on barrier function impaired by ER stress. Importantly, we found that the regulatory effect of glycine on intestinal permeability, proteins implicated in ER stress and apoptosis, as well as the morphological alterations of the ER were reversed by rapamycin. In summary, our results indicated that glycine alleviates ER stress-induced apoptosis and intestinal barrier dysfunction in IPEC-1 cells in a mammalian target of rapamycin complex 1 (mTORC1)-dependent manner. The data provides in vitro evidence and a mechanism for the protective effect of glycine against the disruption of intestinal barrier integrity induced by ER stress.

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Section: Introductionsupporting

confidence: 94%

Glycine represses endoplasmic reticulum stress-related apoptosis and improves intestinal barrier by activating mammalian target of rapamycin complex 1 signaling

Yang

Fan

et al. 2022

Animal Nutrition

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“…[ 27 ] It has been reported that the overexpression of ENDO-VEGI fusion protein achieved a strong inhibition effect on angiogenesis. [ 8 ] And Pan et al [ 28 ] discovered that ENDO-VEGI chimeric recombinant adenovirus exhibited significant inhibiting efficacy on neovascularization. The former 2 studies revealed that recombinant adenovirus had an effect on angiogenesis which could further influence inflammatory responses.…”

Section: Discussionmentioning

confidence: 99%

“…Severe ER stress induced by Hcy causes cell apoptosis, metabolic disorders, inflammation, and so on. [ 8 ] An elevated level of total homocysteine (tHcy) in blood can serve as a strong risk factor for atherosclerotic vascular disease in the coronary, cerebral, and peripheral vessels, and for arterial and venous thromboembolism as well as cognitive decline, dementia, and Alzheimer disease. [ 9 ] Thus, to explore the possible mechanism and molecular of protecting VECs from Hcy-induced injury is essential for the treatment of vascular diseases.…”

Section: Introductionmentioning

confidence: 99%

Antagonistic effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenovirus on homocysteine-induced vascular endothelial cells injury in vitro and in vivo

Cui

Liu²,

Yao³

2016

Medicine

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Background:The study is inclined to investigate the antagonistic effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenovirus (Ad-hENDO-VEGI) on homocysteine (Hcy)-induced vascular endothelial cells (VECs) injury in vitro and in vivo.Methods:Human VECs cell line ECV304 was selected and infected with Ad-hENDO-VEGI. The LDH leakage, SOD activity, and MDA levels were measured by the automatic biochemical analyzer. Cell survival rate was counted by Trypanblau dying. The TNF-α and MCP-1 protein expressions were detected by ELISA assay. The protein expressions of fusion protein of Ad-hENDO-VEGI, nuclear factor kappa B p65 (NF-kappa B p65), and NF-kappa B inhibitor alpha (I-kappa B-α) were detected by Western blotting. A rat model of hyper-homocysteinemia was constructed. Thirty-six Wistar rats were randomly divided into 3 groups: the control group, the model group, and the Ad-hENDO-VEGI group. Serum Hcy levels in rats were measured with enzymatic cycling method. Endothelial vasodilation function was evaluated with the treatment of sodium nitroprusside and acetylcholine.Results:After Ad-hENDO-VEGI infection, high expressions (41 kD) of fusion proteins in ECV304 cells were observed. The injury severity of Hcy on ECV304 cells had a dose-dependent manner, and the injury reached a steady stage at 1.0 mmol/L. Thus, 1.0 mmol/L Hcy was selected for further experiments. With an increase of Ad-hENDO-VEGI in ECV304 cells after Hcy treatment, LDH leakage, MDA, TNF-α, MCP-1, and nuclear NF-kappa B p65 protein expression were gradually decreased, and cell survival rate, SOD activity, and I-kappa B-α protein expression were gradually increased. Compared with the control group, the model group had a higher Hcy level and attenuated vasodilator response. The Ad-hENDO-VEGI group exhibited a lower Hcy level and enhanced vasodilator response than the model group.Conclusion:These results indicated that Ad-hENDO-VEGI could down-regulate NF-kappa B p65 expression and suppress inflammatory response, thereby alleviating Hcy-induced VECs injury.

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“…L‐serine, which is also widely used in the food, cosmetics, and pharmaceutical industries, [ 80–82 ] is another α ‐amino acid that can be directly synthesized through the rTHF‐rgcv pathway in the formatotrophic E. coli strain (Figure 4). In order to efficiently produce L‐serine using the formatotrophic E. coli strain, fine‐tuning of the expression level of the sda gene using metabolic engineering strategies, such as sRNA [ 59 ] or CRISPRi, [ 83 ] is necessary since Sda is an important enzyme influencing both formatotrophic growth and L‐serine production.…”

Section: Opportunities For the Production Of Chemicals Using The Synthetic Formatotrophmentioning

confidence: 99%

Synthetic Formatotrophs for One‐Carbon Biorefinery

et al. 2021

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The use of CO2 as a carbon source in biorefinery is of great interest, but the low solubility of CO2 in water and the lack of efficient CO2 assimilation pathways are challenges to overcome. Formic acid (FA), which can be easily produced from CO2 and more conveniently stored and transported than CO2, is an attractive CO2‐equivalent carbon source as it can be assimilated more efficiently than CO2 by microorganisms and also provides reducing power. Although there are native formatotrophs, they grow slowly and are difficult to metabolically engineer due to the lack of genetic manipulation tools. Thus, much effort is exerted to develop efficient FA assimilation pathways and synthetic microorganisms capable of growing solely on FA (and CO2). Several innovative strategies are suggested to develop synthetic formatotrophs through rational metabolic engineering involving new enzymes and reconstructed FA assimilation pathways, and/or adaptive laboratory evolution (ALE). In this paper, recent advances in development of synthetic formatotrophs are reviewed, focusing on biological FA and CO2 utilization pathways, enzymes involved and newly developed, and metabolic engineering and ALE strategies employed. Also, future challenges in cultivating formatotrophs to higher cell densities and producing chemicals from FA and CO2 are discussed.

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Inhibition of homocysteine-induced endoplasmic reticulum stress and endothelial cell damage by l-serine and glycine

Cited by 20 publications

References 28 publications

Glycine represses endoplasmic reticulum stress-related apoptosis and improves intestinal barrier by activating mammalian target of rapamycin complex 1 signaling

Glycine represses endoplasmic reticulum stress-related apoptosis and improves intestinal barrier by activating mammalian target of rapamycin complex 1 signaling

Antagonistic effects of endostatin-vascular endothelial growth inhibitor chimeric recombinant adenovirus on homocysteine-induced vascular endothelial cells injury in vitro and in vivo

Synthetic Formatotrophs for One‐Carbon Biorefinery

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