SIRT 1 binding with PKM and NSE and modulate their acetylation and activities
| Autor: | Xiao-Hui Xu, Yue-rong Wang, Hai Huang, Xiu-Ling Liu, Zhaohuan Zhang, Hui Zhang |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Agonist medicine.drug_class Pyruvate Kinase Carbazoles Biophysics Heterocyclic Compounds 4 or More Rings Biochemistry Neuroprotection DNA-binding protein Catalysis Analytical Chemistry Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine SRT1720 Sirtuin 1 medicine Animals Glycolysis KEGG Molecular Biology Chemistry Brain Acetylation Rats Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology Phosphopyruvate Hydratase hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Pyruvate kinase Protein Binding |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics. 1867:794-801 |
| ISSN: | 1570-9639 |
| DOI: | 10.1016/j.bbapap.2019.06.003 |
| Popis: | SIRT1 (Silent mating type information regulation 2 homolog 1) play a neuroprotective effect through deacetylation target proteins in various neuronal diseases. However, the precise mechanisms remain elusive. In this study, we aim to identify those novel interacting partners of SIRT1 in rat brain tissue. By using a pre-clear GST-Pull down assay followed by the LC-MS/MS analysis, we've identified potential SIRT1's interacting partners, which function annotation by GO and KEGG analysis indicating some metabolic pathways are among the most enriched. Then we confirmed two candidates Enolase-1 (and NSE (Neuron-Specific Enolase) in brain) and PKM (Pyruvate Kinase Muscle) are associated with SIRT1 in brain tissue lysis by co-immunoprecipitation. Furthermore, increase or decrease the SIRT1 enzyme activity by its agonist SRT1720 or antagonist EX527 could significantly affect the acetylation level of endogenous NSE and PKM, SIRT1 overexpression or knock out expreiments also showed the same results as use SIRT1's agonist or antagonist. Moreover, the acetylation changes on NSE or PKM could finally lead to affection on their catalytic activity. Taken together, our findings suggest that the function of SIRT1 binding proteins is enriched in metabolic pathways. NSE and PKM are new SIRT1 binding molecules. SIRT1 may regulate acetylation level of NSE and PKM through deacetylation and further regulate their catalytic activity. Our study provides new evidence for the involvement of SIRT1 in the mechanisms of metabolic regulation in central nervous system. |
| Databáze: | OpenAIRE |
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