ArticlePloS one2018
Protective effect of 3-hydroxybutyrate against endoplasmic reticulum stress-associated vascular endothelial cell damage induced by low glucose exposure.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 15 citations in OpenAlex.
- Endoplasmic Reticulum Stress-induced Endothelial Dysfunction Promotes Neointima Formation after Arteriovenous Grafts in Mice on High-fat Diet.Current medical science · 2023Article
- The proteomic effects of ketone bodies: implications for proteostasis and brain proteinopathies.Frontiers in molecular neuroscience · 2023Review
- Ischemic brain injury in diabetes and endoplasmic reticulum stress.Neurochemistry international · 2022Review
- Liver circadian clock disruption alters perivascular adipose tissue gene expression and aortic function in mice.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought?The international journal of neuropsychopharmacology · 2020Review
- The potential contribution of impaired brain glucose metabolism to congenital Zika syndrome.Journal of anatomy · 2019Review
- Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisThe aim of this study was to elucidate the mechanism by which severe hypoglycemia accelerates vascular complications. Furthermore, we assessed the possible protective effect of ketone bodies against the endothelial cell damage caused by glucose deficiency.
methodsHuman umbilical vein endothelial cells (HUVECs) were cultured at a glucose level of either 0.56 or 5.6 mmol/L with or without 3-hydroxybutyrate (3-HB) supplementation. Cell viability was assessed with a CCK-8 assay and a lactate dehydrogenase (LDH) release assay. The activity of caspases was measured using fluorogenic substrates. The expression of genes associated with endothelial cell function and endoplasmic reticulum (ER) stress was evaluated by real-time quantitative PCR. Protein levels of ER stress-related molecules were assessed by Western blotting.
resultsCulture of HUVECs in low-glucose medium for 24 or 48 h resulted in reduction of cell viability accompanied by activation of caspase-3/7 and caspase-8. The addition of a pan caspase inhibitor attenuated the cell death. After incubation in the low-glucose medium, we found reduced mRNA and protein levels of endothelial nitric oxide synthase. ER stress responses mediated by phosphorylation of protein kinase RNA-like ER kinase (PERK) and cleavage of activating transcription factor 6 (ATF6) were augmented, but X-box binding protein 1 (Xbp1) splicing was reduced. Most of these responses to glucose deficiency were significantly attenuated by supplementation with 3-HB. CONCLUSIONS/
interpretationThese observations showed that exposure to low glucose induces ER stress, caspase activation, endothelial cell dysfunction and cell death. The beneficial effects of 3-HB shown in this study suggest that hypoketonemic severe hypoglycemia induced by insulin injections or insulin secretagogue administration may be more harmful than hyperketonemic severe hypoglycemia.
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