PMID- 31523993 OWN - NLM STAT- MEDLINE DCOM- 20200204 LR - 20221207 IS - 2169-141X (Electronic) IS - 2169-1401 (Linking) VI - 47 IP - 1 DP - 2019 Dec TI - Matrine derivate MASM protects murine MC3T3-E1 osteoblastic cells against dexamethasone-induced apoptosis via the regulation of USP14/p53. PG - 3720-3728 LID - 10.1080/21691401.2019.1664563 [doi] AB - Matrine derivative MASM (M19) is a quinolizine alkaloid with diverse pharmacological effects including preventing postmenopausal osteoporosis. In the current study, we observed that pretreatment with M19 inhibited cell apoptosis of murine osteoblastic MC3T3-E1 and primary osteoblasts induced by 1 muM dexamethasone in a dose-dependent manner. Our study also showed that pretreatment with M19 significantly prevented the upregulation of p53 that is caused by dexamethasone but had no effect on the p53 mRNA expression levels. Further immunoprecipitation (IP) experiments showed that M19 treatment increases the ubiquitination of p53 in dexamethasone-treated MC3T3-E1 cells. The expression of USP14, a deubiquitinating enzyme, increased with dexamethasone and decreased with M19 pretreatment. Co-IP experiments demonstrated the interaction between USP14 and p53, and the induced effect of a USP14 inhibitor (IU1) on p53 ubiquitination, which indicated that USP14 is a potential deubiquitinase for p53. Furthermore, pretreatment with IU1 or a p53 inhibitor (PFT-alpha) partially blocked dexamethasone-induced apoptosis of MC3T3-E1 cells. The overexpression of USP14 or p53 reversed the antiapoptotic effect of M19 in dexamethasone-treated MC3T3-E1 cells. In addition, PFT-alpha treatment remarkably blocked the effects of USP14 overexpression. In summary, our findings suggest that M19 exerts protective effects on dexamethasone-treated MC3T3-E1 cells by regulating USP14/p53. FAU - Zhou, Panyu AU - Zhou P AD - Department of Emergency, Changhai Hospital, Naval Military Medical University , Shanghai , China. AD - Department of Orthopedics, Changhai Hospital, Naval Military Medical University , Shanghai , China. FAU - Xia, Demeng AU - Xia D AD - Department of Emergency, Changhai Hospital, Naval Military Medical University , Shanghai , China. FAU - Wang, Yang AU - Wang Y AD - Department of Emergency, Changhai Hospital, Naval Military Medical University , Shanghai , China. AD - Department of Orthopedics, Changhai Hospital, Naval Military Medical University , Shanghai , China. FAU - Lv, Hongdi AU - Lv H AD - Department of Logistics, The Nine Nine Zero Hospital of the People's Liberation Army , Henan , China. FAU - Wang, Ziqin AU - Wang Z AD - Department of Nutrition, Armed Police Henan Corps Hospital , Henan , China. FAU - Xing, Malcolm AU - Xing M AD - College of Mechanical Engineering, University of Manitoba , Winnipeg , Canada. FAU - Zhao, Qingjie AU - Zhao Q AD - Department of Organic Chemistry, School of Pharmcy, Naval Military Medical University , Shanghai , China. FAU - Xu, Shuogui AU - Xu S AD - Department of Emergency, Changhai Hospital, Naval Military Medical University , Shanghai , China. AD - Department of Orthopedics, Changhai Hospital, Naval Military Medical University , Shanghai , China. LA - eng PT - Journal Article PL - England TA - Artif Cells Nanomed Biotechnol JT - Artificial cells, nanomedicine, and biotechnology JID - 101594777 RN - 0 (Alkaloids) RN - 0 (Quinolizines) RN - 0 (Tumor Suppressor Protein p53) RN - 0 (Usp14 protein, mouse) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 3.4.19.12 (Ubiquitin Thiolesterase) RN - 0 (Matrines) SB - IM MH - 3T3 Cells MH - Alkaloids/*pharmacology MH - Animals MH - Apoptosis/*drug effects MH - Cytoprotection/drug effects MH - Dexamethasone/*adverse effects MH - Mice MH - Osteoblasts/*cytology/*drug effects/metabolism MH - Quinolizines/*pharmacology MH - Tumor Suppressor Protein p53/*metabolism MH - Ubiquitin Thiolesterase/*metabolism MH - Ubiquitination/drug effects MH - Up-Regulation/drug effects MH - Matrines OTO - NOTNLM OT - Matrine OT - USP14 OT - dexamethasone OT - osteoblast OT - ubiquitination EDAT- 2019/09/17 06:00 MHDA- 2020/02/06 06:00 CRDT- 2019/09/17 06:00 PHST- 2019/09/17 06:00 [entrez] PHST- 2019/09/17 06:00 [pubmed] PHST- 2020/02/06 06:00 [medline] AID - 10.1080/21691401.2019.1664563 [doi] PST - ppublish SO - Artif Cells Nanomed Biotechnol. 2019 Dec;47(1):3720-3728. doi: 10.1080/21691401.2019.1664563.