PMID- 37806254 OWN - NLM STAT- MEDLINE DCOM- 20231101 LR - 20231105 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 682 DP - 2023 Nov 19 TI - SIRT1 Asn346 sugar chain promoting collagen deacetylation protective effect on osteoblasts under stress. PG - 148-155 LID - S0006-291X(23)01111-7 [pii] LID - 10.1016/j.bbrc.2023.09.075 [doi] AB - Silencing type information regulator homolog 1 (SIRT1) is a class of nicotinamide adenine dinucleotide (NAD(+)) dependent deacetylases, which is the convergence point of important physiological processes in vivo, namely, osteoblast aging, energy metabolism, and bone remodeling. To verify whether the O-acetylglucosamine (O-GlcNAc) modification of SIRT1 in the nucleus of osteoblasts enhances its deacetylase activity under stress and protects osteoblasts through the RANK/RANKL signaling pathway by collagen deacetylation. The R language and online data research identified SIRT1 as being involved in bone metabolism. Enrichment analysis showed that SIRT1 is involved in osteoblast transcription, apoptosis, and deacetylation pathways. Interactive Immuno-blotting and immunofluorescence experiments revealed that SIRT1 and O-glycosylation catalytic enzyme (OGT) were localized in the nucleus. Mass Spectrometry analysis showed that O-glycosylation occurred on the asparagine at the 346th position of SIRT1, and N346(th) was located in the central domain of SIRT1. Furthermore, the protein structure analysis of PyMol also proved that the OGT binding region was in the central domain of SIRT1. Under physiological conditions, both wtSIRT1 and SIRT1(N346R) can inhibit RANKL-mediated transcriptional activation. The RT-PCR detection results showed that wtSIRT1 reduced RANKL transcription under the conditions of apoptotic agent treatment. The finding that SIRT1 can regulate the physiological process of bone remodeling through the RANK/RANKL signaling pathway in osteoblasts under stress. The O-glycosylation and deacetylation activity of SIRT1 significantly increased, regulating the balance between osteoblast survival and apoptosis by deacetylation of key proteins such as RANKL. CI - Copyright (c) 2023 Elsevier Inc. All rights reserved. FAU - Cai, Min AU - Cai M AD - Department of Geriatric Medicine, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China. FAU - Chen, Yaoqi AU - Chen Y AD - Department of Geriatric Medicine, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China; Department of Endocrinology, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China. FAU - Lin, Yiting AU - Lin Y AD - Department of Geriatric Medicine, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China; Department of Endocrinology, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China. FAU - Hu, Zhangjie AU - Hu Z AD - Department of Geriatric Medicine, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China; Department of Endocrinology, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China. FAU - Li, Lizhi AU - Li L AD - Department of Geriatric Medicine, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China; Department of Pediatric Surgery, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China. FAU - Huang, Huping AU - Huang H AD - Department of Gastroenterology, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China. Electronic address: huanghuping@fjmu.edu.cn. FAU - Lin, Jianli AU - Lin J AD - Department of Endocrinology, Fujian Provincial Hospital, Shengli Clinical Medical College, Fujian Medical University, Fuzhou, Fujian, China. Electronic address: linjianli@hotmail.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20231004 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - EC 3.5.1.- (Sirtuin 1) RN - 0 (Sugars) RN - 0 (Collagen Type I) RN - 0U46U6E8UK (NAD) SB - IM MH - *Sirtuin 1/genetics/metabolism MH - *Sugars/metabolism MH - Collagen Type I/metabolism MH - NAD/metabolism MH - Osteoblasts/metabolism OTO - NOTNLM OT - Bone metabolism OT - Deacetylation OT - Osteoblast OT - Osteoporosis OT - SIRT1 COIS- Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2023/10/09 00:41 MHDA- 2023/11/01 12:44 CRDT- 2023/10/08 18:18 PHST- 2023/09/04 00:00 [received] PHST- 2023/09/22 00:00 [revised] PHST- 2023/09/25 00:00 [accepted] PHST- 2023/11/01 12:44 [medline] PHST- 2023/10/09 00:41 [pubmed] PHST- 2023/10/08 18:18 [entrez] AID - S0006-291X(23)01111-7 [pii] AID - 10.1016/j.bbrc.2023.09.075 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2023 Nov 19;682:148-155. doi: 10.1016/j.bbrc.2023.09.075. Epub 2023 Oct 4.