دورية أكاديمية
Multiomics analysis reveals serine catabolism as a potential therapeutic target for MELAS.
| العنوان: | Multiomics analysis reveals serine catabolism as a potential therapeutic target for MELAS. |
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| المؤلفون: | Liufu T; Department of Neurology, Peking University First Hospital, Beijing, China., Zhao X; Department of Neurology, Peking University First Hospital, Beijing, China., Yu M; Department of Neurology, Peking University First Hospital, Beijing, China., Xie Z; Department of Neurology, Peking University First Hospital, Beijing, China., Meng L; Department of Neurology, Peking University First Hospital, Beijing, China., Lv H; Department of Neurology, Peking University First Hospital, Beijing, China., Zhang W; Department of Neurology, Peking University First Hospital, Beijing, China., Yuan Y; Department of Neurology, Peking University First Hospital, Beijing, China.; Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China., Xing G; Neuroscience Research Institute, Peking University, Beijing, China., Deng J; Department of Neurology, Peking University First Hospital, Beijing, China.; Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China.; Key Laboratory for Neuroscience, Ministry of Education/National Health Commission, Peking University, Beijing, China., Wang Z; Department of Neurology, Peking University First Hospital, Beijing, China.; Beijing Key Laboratory of Neurovascular Disease Discovery, Beijing, China. |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Jun 30; Vol. 38 (12), pp. e23742. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | MELAS Syndrome*/metabolism , MELAS Syndrome*/genetics , MELAS Syndrome*/pathology , Glycine Hydroxymethyltransferase*/metabolism , Glycine Hydroxymethyltransferase*/genetics , Serine*/metabolism, Humans ; Myoblasts/metabolism ; NAD/metabolism ; Male ; Proteomics/methods ; Female ; Transcriptome ; Multiomics |
| مستخلص: | Mitochondrial disease is a devastating genetic disorder, with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and m.3243A>G being the most common phenotype and genotype, respectively. The treatment for MELAS patients is still less effective. Here, we performed transcriptomic and proteomic analysis in muscle tissue of MELAS patients, and discovered that the expression of molecules involved in serine catabolism were significantly upregulated, and serine hydroxymethyltransferase 2 (SHMT2) increased significantly in both the mRNA and protein levels. The SHMT2 protein level was also increased in myoblasts with m.3243A>G mutation, which was transdifferentiated from patients derived fibroblasts, accompanying with the decreased nicotinamide adenine dinucleotide (NAD + )/reduced NAD + (NADH) ratio and cell viability. After treating with SHMT2 inhibitor (SHIN1), the NAD + /NADH ratio and cell viability in MELAS myoblasts increased significantly. Taken together, our study indicates that enhanced serine catabolism plays an important role in the pathogenesis of MELAS and that SHIN1 can be a potential small molecule for the treatment of this disease. (© 2024 Federation of American Societies for Experimental Biology.) |
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| معلومات مُعتمدة: | 82071409 MOST | National Natural Science Foundation of China (NSFC); 82171846 MOST | National Natural Science Foundation of China (NSFC); U20A20356 MOST | National Natural Science Foundation of China (NSFC); 20220484017 Beijing Nova Program; 20230484403 Beijing Nova Program; 2023HQ03 National High Level Hospital Clinical Research Funding; 2023CX05 National High Level Hospital Clinical Research Funding |
| فهرسة مساهمة: | Keywords: M.3243 A>G; MELAS; NADH; SHIN1; SHMT2; multiomics |
| المشرفين على المادة: | EC 2.1.2.1 (Glycine Hydroxymethyltransferase) 452VLY9402 (Serine) EC 2.1.2.1 (SHMT protein, human) 0U46U6E8UK (NAD) |
| تواريخ الأحداث: | Date Created: 20240612 Date Completed: 20240612 Latest Revision: 20240612 |
| رمز التحديث: | 20240613 |
| DOI: | 10.1096/fj.202302286RRR |
| PMID: | 38865203 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.202302286RRR |