CRIF1 Deficiency Increased Homocysteine Production by Disrupting Dihydrofolate Reductase Expression in Vascular Endothelial Cells
| العنوان: | CRIF1 Deficiency Increased Homocysteine Production by Disrupting Dihydrofolate Reductase Expression in Vascular Endothelial Cells |
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| المؤلفون: | Byeong Hwa Jeon, Harsha Nagar, Su-jeong Choi, Cuk-Seong Kim, Shuyu Piao, Seonhee Kim, Kaikobad Irani, Ikjun Lee, Sang-Ha Oh |
| المصدر: | Antioxidants, Vol 10, Iss 1645, p 1645 (2021) Antioxidants Volume 10 Issue 11 |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | medicine.medical_specialty, Homocysteine, Physiology, Clinical Biochemistry, RM1-950, Biochemistry, Article, Umbilical vein, chemistry.chemical_compound, folic acid, Downregulation and upregulation, dihydrofolate reductase, Internal medicine, Dihydrofolate reductase, medicine, Endothelial dysfunction, Molecular Biology, Gene knockdown, biology, fungi, food and beverages, Cell Biology, homocysteine, medicine.disease, Endothelial stem cell, Endocrinology, chemistry, biology.protein, CR6 interacting factor 1, Therapeutics. Pharmacology, Intracellular |
| الوصف: | Elevated plasma homocysteine levels can induce vascular endothelial dysfunction however, the mechanisms regulating homocysteine metabolism in impaired endothelial cells are currently unclear. In this study, we deleted the essential mitoribosomal gene CR6 interacting factor 1 (CRIF1) in human umbilical vein endothelial cells (HUVECs) and mice to induce endothelial cell dysfunction then, we monitored homocysteine accumulation. We found that CRIF1 downregulation caused significant increases in intracellular and plasma concentrations of homocysteine, which were associated with decreased levels of folate cycle intermediates such as 5-methyltetrahydrofolate (MTHF) and tetrahydrofolate (THF). Moreover, dihydrofolate reductase (DHFR), a key enzyme in folate-mediated metabolism, exhibited impaired activity and decreased protein expression in CRIF1 knockdown endothelial cells. Supplementation with folic acid did not restore DHFR expression levels or MTHF and homocysteine concentrations in endothelial cells with a CRIF1 deletion or DHFR knockdown. However, the overexpression of DHFR in CRIF1 knockdown endothelial cells resulted in decreased accumulation of homocysteine. Taken together, our findings suggest that CRIF1-deleted endothelial cells accumulated more homocysteine, compared with control cells this was primarily mediated by the disruption of DHFR expression. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 2076-3921 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e9189b98c87589cb9eef74d70a0fedb6Test https://www.mdpi.com/2076-3921/10/11/1645Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....e9189b98c87589cb9eef74d70a0fedb6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20763921 |
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