PMID- 31616293
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1663-9812 (Print)
IS  - 1663-9812 (Electronic)
IS  - 1663-9812 (Linking)
VI  - 10
DP  - 2019
TI  - Panax Notoginseng Saponins Protect Cardiac Myocytes Against Endoplasmic Reticulum 
      Stress and Associated Apoptosis Through Mediation of Intracellular Calcium 
      Homeostasis.
PG  - 1013
LID - 10.3389/fphar.2019.01013 [doi]
LID - 1013
AB  - Endoplasmic reticulum (ER) stress has been demonstrated to play important roles 
      in the pathogenesis of various cardiovascular diseases. The ER stress pathway is 
      therefore a promising therapeutic target in cardiovascular disease. Although 
      Panax notoginseng saponins (PNS) are one of the patent medicines that are 
      traditionally used to treat cardiovascular disorders, their effects on ER stress 
      in cardiac myocytes remain unexploited so far. This study investigates the 
      effects of PNS on ER stress and its associated cell apoptosis along with the 
      related mechanism in cardiac myocytes. PNS compounds were identified via 
      high-performance liquid chromatograph (HPLC) assay. PNS-pretreated H9c2 cells, 
      HL-1 cells, and primary cultured neonatal rat cardiomyocytes were stimulated with 
      thapsigargin (TG) to induce ER stress response and apoptosis. ER stress response 
      was tested by immunofluorescence or immunoblot of the ER protein 
      chaperones-calnexin, binding immunoglobulin protein (BiP) and the C/EBP 
      homologous protein (CHOP). Cell viability was tested by methyl thiazolyl 
      tetrazolium (MTT) assay. Cell apoptosis was detected by immunoblot of Cleaved 
      caspase-3 and flow cytometry analysis of Annexin V/propidium iodide (PI) 
      staining. Cytosolic, mitochondrial, and ER calcium dynamics were investigated by 
      calcium imaging. Moreover, a ryanodine receptor type-2 (RyR(2)) overexpression 
      stable cell line was generated to verify the mechanism of RyR(2) involved in PNS 
      in the inhibition of ER stress and cell apoptosis. We demonstrate here that PNS 
      protected cardiac myocytes from ER stress response and associated cell death in a 
      concentration-dependent manner. Importantly, PNS reduced the elevation of 
      cytosolic calcium, mitochondria calcium, as well as ER calcium in response to 
      either TG or histamine treatment. PNS protection in ER stress was regulated by 
      RyR(2) expression. In summary, PNS protection against TG-induced ER stress 
      response and its associated cell apoptosis in cardiac myocytes is calcium 
      dependent. Through the regulation of ER calcium release mediated by RyR(2), a 
      novel mechanism for PNS in the prevention of cardiovascular diseases is thereby 
      identified.
CI  - Copyright (c) 2019 Chen, Xue, Li, Xiao, Shangguan, Zhang, Bai, Liu and Li.
FAU - Chen, Jun
AU  - Chen J
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Xue, Rui
AU  - Xue R
AD  - Medical Research Center, The First Affiliated Hospital of Zhengzhou University, 
      Zhengzhou, China.
FAU - Li, Li
AU  - Li L
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Xiao, Li Li
AU  - Xiao LL
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Shangguan, Jiahong
AU  - Shangguan J
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Zhang, Wenjing
AU  - Zhang W
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Bai, Xueyang
AU  - Bai X
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Liu, Gangqiong
AU  - Liu G
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
FAU - Li, Ling
AU  - Li L
AD  - Vasculocardiology Department, The First Affiliated Hospital of Zhengzhou 
      University, Zhengzhou, China.
LA  - eng
PT  - Journal Article
DEP - 20190920
PL  - Switzerland
TA  - Front Pharmacol
JT  - Frontiers in pharmacology
JID - 101548923
PMC - PMC6764115
OTO - NOTNLM
OT  - Panax notoginseng saponins
OT  - apoptosis
OT  - endoplasmic reticulum stress
OT  - intracellular calcium homeostasis
OT  - ryanodine receptor
EDAT- 2019/10/17 06:00
MHDA- 2019/10/17 06:01
PMCR- 2019/09/20
CRDT- 2019/10/17 06:00
PHST- 2019/03/11 00:00 [received]
PHST- 2019/08/08 00:00 [accepted]
PHST- 2019/10/17 06:00 [entrez]
PHST- 2019/10/17 06:00 [pubmed]
PHST- 2019/10/17 06:01 [medline]
PHST- 2019/09/20 00:00 [pmc-release]
AID - 10.3389/fphar.2019.01013 [doi]
PST - epublish
SO  - Front Pharmacol. 2019 Sep 20;10:1013. doi: 10.3389/fphar.2019.01013. eCollection 
      2019.