PMID- 38056617
OWN - NLM
STAT- MEDLINE
DCOM- 20240108
LR  - 20240108
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 963
DP  - 2024 Jan 15
TI  - A polypeptide derived from pilose antler ameliorates CUMS-induced depression-like 
      behavior by SENP2-PLCbeta4 signaling axis.
PG  - 176247
LID - S0014-2999(23)00761-6 [pii]
LID - 10.1016/j.ejphar.2023.176247 [doi]
AB  - Neurogenesis is known to be closely associated with depression. We aimed to 
      investigate whether a polypeptide monomer derived from pilose antler (polypeptide 
      sequence LSALEGVFYP, PAP) exerts an antidepressant effect by influencing 
      neurogenesis, and to elucidate the mechanism of its antidepressant action. 
      Behavioral tests were performed to observe the antidepressant effect of PAP. 
      Neurogenesis in the dentate gyrus (DG) region of hippocampus was observed by 
      immunofluorescence. The expression of key proteins of Sentrin/SUMO-specific 
      proteases 2 (SENP2)- Phosphoinositide-specific phospholipase C beta 4 (PLCbeta4) 
      pathway was accessed by co-immunoprecipitation (Co-IP), and the calcium 
      homeostasis associated proteins were observed via Western blot (WB). 
      Subsequently, temozolomide (TMZ) pharmacologically blocked neurogenesis to verify 
      the antidepressant effect of PAP on neurogenesis. The mechanism of PAP 
      antidepressant effect was verified by constructing a sh-SENP2 virus vector to 
      silence SENP2 protein. Finally, corticosterone (CORT)-induced PC12 cell model was 
      used to verify whether PAP was involved in the process of deconjugated PLCbeta4 
      SUMOylated. The results showed that PAP improved depression-like behavior and 
      neurogenesis induced by chronic unpredictable mild stimulation (CUMS). In 
      addition, PAP acted on SENP2-PLCbeta4 pathway to deconjugate the SUMOylation of 
      PLCbeta4 and affect calcium homeostasis. Pharmacological blockade of neurogenesis by 
      TMZ treatment impaired the antidepressant efficacy of PAP. Knockout of SENP2 in 
      the CUMS model attenuated the antidepressant response of PAP, and the impaired 
      neurogenesis was not ameliorated by PAP treatment. In summary, PAP acted on the 
      SENP2-PLCbeta4 signaling pathway to inhibit the SUMOylation of PLCbeta4 and maintain 
      calcium homeostasis, thereby protecting neurogenesis and playing an 
      antidepressant role.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Dong, Yu
AU  - Dong Y
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, 
      China; Institute of Literature in Chinese Medicine, Nanjing University of Chinese 
      Medicine, Nanjing, 210023, China.
FAU - Lu, Zihan
AU  - Lu Z
AD  - Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical 
      University, Nanjing, 210009, China.
FAU - Gao, Tiantian
AU  - Gao T
AD  - School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, 
      China.
FAU - Wei, Zhifeng
AU  - Wei Z
AD  - Department of Pharmacology of Chinese Materia Medica, China Pharmaceutical 
      University, Nanjing, 210009, China.
FAU - Ou, Zhijie
AU  - Ou Z
AD  - Neurology Department, Changshu Hospital Affiliated to Nanjing University of 
      Chinese Medicine, Changshu, Jiangsu, 215500, China. Electronic address: 
      sjnk1916@163.com.
FAU - Shi, Zheng
AU  - Shi Z
AD  - Institute of Literature in Chinese Medicine, Nanjing University of Chinese 
      Medicine, Nanjing, 210023, China. Electronic address: 361000@njucm.edu.cn.
FAU - Shen, Jie
AU  - Shen J
AD  - Institute of Literature in Chinese Medicine, Nanjing University of Chinese 
      Medicine, Nanjing, 210023, China. Electronic address: shenjie73@njucm.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20231212
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - EC 3.1.4.11 (Phospholipase C beta)
RN  - EC 3.4.- (Peptide Hydrolases)
RN  - SY7Q814VUP (Calcium)
RN  - 0 (Antidepressive Agents)
RN  - 0 (Peptides)
RN  - EC 3.4.- (Endopeptidases)
SB  - IM
MH  - Animals
MH  - *Depression/drug therapy/etiology/metabolism
MH  - Phospholipase C beta/metabolism
MH  - *Peptide Hydrolases/pharmacology
MH  - Calcium/metabolism
MH  - Antidepressive Agents/pharmacology/therapeutic use/metabolism
MH  - Signal Transduction
MH  - Peptides/pharmacology
MH  - Endopeptidases/metabolism/pharmacology
MH  - Hippocampus
MH  - Stress, Psychological/metabolism
MH  - Disease Models, Animal
OTO - NOTNLM
OT  - CUMS
OT  - Neurogenesis
OT  - PLCbeta4
OT  - Polypeptide monomer
OT  - SENP2
OT  - SUMO2
COIS- Declaration of competing interest The authors declare that they have no conflict 
      of interest.
EDAT- 2023/12/07 00:42
MHDA- 2024/01/08 06:41
CRDT- 2023/12/06 19:24
PHST- 2023/07/20 00:00 [received]
PHST- 2023/11/10 00:00 [revised]
PHST- 2023/11/30 00:00 [accepted]
PHST- 2024/01/08 06:41 [medline]
PHST- 2023/12/07 00:42 [pubmed]
PHST- 2023/12/06 19:24 [entrez]
AID - S0014-2999(23)00761-6 [pii]
AID - 10.1016/j.ejphar.2023.176247 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2024 Jan 15;963:176247. doi: 10.1016/j.ejphar.2023.176247. Epub 
      2023 Dec 12.