PMID- 35725243 OWN - NLM STAT- MEDLINE DCOM- 20230106 LR - 20230127 IS - 2059-8696 (Electronic) IS - 2059-8688 (Print) IS - 2059-8688 (Linking) VI - 7 IP - 6 DP - 2022 Dec TI - Inhibition of the postsynaptic density protein 95 on the protective effect of Ang-(1-7)-Mas on cerebral ischaemia injury. PG - 500-509 LID - 10.1136/svn-2021-001396 [doi] AB - BACKGROUND: Postsynaptic density protein-95 (PSD95) plays an important role in cerebral ischaemia injury, but its mechanism needs further research. This study aimed to explore the role of PSD95 in (Ang-(1-7))-Mas-mediated cerebral ischaemia protection and its regulatory mechanism. METHODS: Oxygen-glucose deprivation (OGD) neuron and rat middle cerebral artery occlusion (MCAO) models were used as in vitro and in vivo models, respectively. TAT-MAS9C was used to disrupt the interaction between PSD95 and Mas. The recombinant PSD95 adenovirus (Ad-PSD95) was used to overexpress PSD95 in neurons. RESULTS: Results showed that in OGD neurons, Ang-(1-7) could promote cell viability; reduce cell apoptosis; reduce the cell membrane localisation of Mas; upregulate the expression levels of pAKT, bcl-2 and I-kappaB; and downregulate the expression levels of Bax, pI-kappaB, tumour necrosis factor alpha and interleukin-1beta. TAT-MAS9C could enhance the aforementioned effects of Ang-(1-7). However, the PSD95 overexpression inhibited the aforementioned effects of Ang-(1-7). In the MCAO rat model, the 2,3,5-triphenyltetrazolium chloride (TTC) staining showed that Ang-(1-7) reduced the infarct volume. The Morris water maze test showed that the number of crossings over the platform area in the Ang-(1-7) group was significantly increased. TAT-MAS9C could promote the protective effect of Ang-(1-7). CONCLUSIONS: Results suggested that PSD95 alleviated the activation of AKT and the inhibition of nuclear factor kappa B signalling pathway mediated by the Ang-(1-7)-Mas complex, thereby reducing neuronal activity, increasing apoptosis and inhibiting the Ang-(1-7)-Mas-mediated cerebral ischaemia protection. CI - (c) Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. FAU - Zhao, Bingrui AU - Zhao B AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. FAU - Wang, Zhe AU - Wang Z AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. FAU - Liang, Xinyue AU - Liang X AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. FAU - Wang, Xiaoyan AU - Wang X AD - College of Intelligence and Information Engineering, Shandong University of Traditional Chinese Medicine, Jinan, Shandong, China. FAU - Lin, Kai AU - Lin K AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. FAU - Yuan, Lihua AU - Yuan L AD - Suzhou Institute of Nano-Tech and Nano-Bionics (SINANO), Chinese Academy of Sciences, Suzhou, Jiangsu, China. FAU - Jiang, Jing AU - Jiang J AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. FAU - Xu, Cong AU - Xu C AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. FAU - Zhang, Daolai AU - Zhang D AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China. FAU - Sun, Yeying AU - Sun Y AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China bian_1005@163.com sunyy@bzmc.edu.cn. FAU - Bian, Weihua AU - Bian W AUID- ORCID: 0000-0003-2369-2073 AD - School of Pharmacy, Binzhou Medical University, Yantai, Shandong, China bian_1005@163.com sunyy@bzmc.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20220620 PL - England TA - Stroke Vasc Neurol JT - Stroke and vascular neurology JID - 101689996 RN - 0 (Disks Large Homolog 4 Protein) SB - IM MH - Rats MH - Animals MH - Disks Large Homolog 4 Protein/metabolism MH - *Brain Ischemia/metabolism MH - Signal Transduction MH - Apoptosis MH - Infarction, Middle Cerebral Artery/pathology MH - *Brain Injuries PMC - PMC9811564 OTO - NOTNLM OT - brain OT - cerebral infarction OT - stroke COIS- Competing interests: None declared. EDAT- 2022/06/21 06:00 MHDA- 2023/01/07 06:00 PMCR- 2022/06/20 CRDT- 2022/06/20 21:07 PHST- 2021/11/03 00:00 [received] PHST- 2022/04/04 00:00 [accepted] PHST- 2022/06/21 06:00 [pubmed] PHST- 2023/01/07 06:00 [medline] PHST- 2022/06/20 21:07 [entrez] PHST- 2022/06/20 00:00 [pmc-release] AID - svn-2021-001396 [pii] AID - 10.1136/svn-2021-001396 [doi] PST - ppublish SO - Stroke Vasc Neurol. 2022 Dec;7(6):500-509. doi: 10.1136/svn-2021-001396. Epub 2022 Jun 20.