دورية أكاديمية
miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2.
| العنوان: | miR-497 and miR-302b regulate ethanol-induced neuronal cell death through BCL2 protein and cyclin D2. |
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| المؤلفون: | Yadav S; Developmental Toxicology Division, Indian Institute of Toxicology Research (CSIR-IITR), MG Marg-80, Lucknow 226001, India. sanjay@iitr.res.in, Pandey A, Shukla A, Talwelkar SS, Kumar A, Pant AB, Parmar D |
| المصدر: | The Journal of biological chemistry [J Biol Chem] 2011 Oct 28; Vol. 286 (43), pp. 37347-57. Date of Electronic Publication: 2011 Aug 30. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology |
| مواضيع طبية MeSH: | Apoptosis/*drug effects , Central Nervous System Depressants/*pharmacology , Cyclin D2/*metabolism , Ethanol/*pharmacology , MicroRNAs/*metabolism , Neurons/*metabolism , Proto-Oncogene Proteins c-bcl-2/*metabolism, 3' Untranslated Regions/genetics ; Apoptosis/genetics ; Cell Line, Tumor ; Cyclin D2/genetics ; Cytochromes c/genetics ; Cytochromes c/metabolism ; Gene Expression Regulation/drug effects ; Gene Expression Regulation/genetics ; Humans ; Membrane Potential, Mitochondrial/drug effects ; Membrane Potential, Mitochondrial/genetics ; MicroRNAs/genetics ; Neurons/cytology ; Proto-Oncogene Proteins c-bcl-2/genetics ; Reactive Oxygen Species/metabolism ; Time Factors |
| مستخلص: | In chronic alcoholism, brain shrinkage and cognitive defects because of neuronal death are well established, although the sequence of molecular events has not been fully explored yet. We explored the role of microRNAs (miRNAs) in ethanol-induced apoptosis of neuronal cells. Ethanol-sensitive miRNAs in SH-SY5Y, a human neuroblastoma cell line, were identified using real-time PCR-based TaqMan low-density arrays. Long-term exposure to ethanol (0.5% v/v for 72 h) produced a maximum increase in expression of miR-497 (474-fold) and miR-302b (322-fold). Similar to SH-SY5Y, long-term exposure to ethanol induced miR-497 and miR-302b in IMR-32, another human neuroblastoma cell line. Using in silico approaches, BCL2 and cyclin D2 (CCND2) were identified as probable target genes of these miRNAs. Cotransfection studies with 3'-UTR of these genes and miRNA mimics have demonstrated that BCL2 is a direct target of miR-497 and that CCND2 is regulated negatively by either miR-302b or miR-497. Overexpression of either miR-497 or miR-302b reduced expression of their identified target genes and increased caspase 3-mediated apoptosis of SH-SY5Y cells. However, overexpression of only miR-497 increased reactive oxygen species formation, disrupted mitochondrial membrane potential, and induced cytochrome c release (mitochondria-related events of apoptosis). Moreover, ethanol induced changes in miRNAs, and their target genes were substantially prevented by pre-exposure to GSK-3B inhibitors. In conclusion, our studies have shown that ethanol-induced neuronal apoptosis follows both the mitochondria-mediated (miR-497- and BCL2-mediated) and non-mitochondria-mediated (miR-302b- and CCND2-mediated) pathway. |
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| المشرفين على المادة: | 0 (3' Untranslated Regions) 0 (CCND2 protein, human) 0 (Central Nervous System Depressants) 0 (Cyclin D2) 0 (MIRN302A microRNA, human) 0 (MIRN497 microRNA, human) 0 (MicroRNAs) 0 (Proto-Oncogene Proteins c-bcl-2) 0 (Reactive Oxygen Species) 3K9958V90M (Ethanol) 9007-43-6 (Cytochromes c) |
| تواريخ الأحداث: | Date Created: 20110901 Date Completed: 20111215 Latest Revision: 20240317 |
| رمز التحديث: | 20240317 |
| مُعرف محوري في PubMed: | PMC3199482 |
| DOI: | 10.1074/jbc.M111.235531 |
| PMID: | 21878650 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1083-351X |
|---|---|
| DOI: | 10.1074/jbc.M111.235531 |