PMID- 26612298
OWN - NLM
STAT- MEDLINE
DCOM- 20161213
LR  - 20181202
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Print)
IS  - 0366-6999 (Linking)
VI  - 128
IP  - 23
DP  - 2015 Dec 5
TI  - Exenatide Reduces Tumor Necrosis Factor-alpha-induced Apoptosis in Cardiomyocytes by 
      Alleviating Mitochondrial Dysfunction.
PG  - 3211-8
LID - 10.4103/0366-6999.170259 [doi]
AB  - BACKGROUND: Tumor necrosis factor-alpha (TNF-alpha) plays an important role in 
      progressive contractile dysfunction in several cardiac diseases. The cytotoxic 
      effects of TNF-alpha are suggested to be partly mediated by reactive oxygen species 
      (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or 
      its analogue exhibits protective effects on the cardiovascular system. The 
      objective of the study was to assess the effects of exenatide, a GLP-1 analogue, 
      on oxidative stress, and apoptosis in TNF-alpha-treated cardiomyocytes in vitro. 
      METHODS: Isolated neonatal rat cardiomyocytes were divided into three groups: 
      Control group, with cells cultured in normal conditions without intervention; 
      TNF-alpha group, with cells incubated with TNF-alpha (40 ng/ml) for 6, 12, or 24 h 
      without pretreatment with exenatide; and exenatide group, with cells pretreated 
      with exenatide (100 nmol/L) 30 mins before TNF-alpha (40 ng/ml) stimulation. We 
      evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick 
      end labeling (TUNEL) assay and flow cytometry, measured ROS production and 
      mitochondrial membrane potential (MMP) by specific the fluorescent probes, and 
      assessed the levels of proteins by Western blotting for all the groups. RESULTS: 
      Exenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured 
      by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited 
      excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c 
      release and cleaved caspase-3 expression and increased bcl-2 expression with 
      concomitantly decreased Bax activation were observed in exenatide-pretreated 
      cultures. CONCLUSION: These results suggested that exenatide exerts a protective 
      effect on cardiomyocytes, preventing TNF-alpha-induced apoptosis; the anti-apoptotic 
      effects may be associated with protection of mitochondrial function.
FAU - Cao, Yuan-Yuan
AU  - Cao YY
FAU - Chen, Zhang-Wei
AU  - Chen ZW
FAU - Gao, Yan-Hua
AU  - Gao YH
FAU - Wang, Xing-Xu
AU  - Wang XX
FAU - Ma, Jian-Ying
AU  - Ma JY
FAU - Chang, Shu-Fu
AU  - Chang SF
FAU - Qian, Ju-Ying
AU  - Qian JY
AD  - Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, 
      Zhongshan Hospital, Fudan University, Shanghai 200032, China.
FAU - Ge, Jun-Bo
AU  - Ge JB
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Peptides)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Venoms)
RN  - 9P1872D4OL (Exenatide)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cells, Cultured
MH  - Exenatide
MH  - In Situ Nick-End Labeling
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria/drug effects
MH  - Myocytes, Cardiac/cytology/*drug effects
MH  - Oxidative Stress/drug effects
MH  - Peptides/*pharmacology
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Venoms/*pharmacology
PMC - PMC4794880
EDAT- 2015/11/28 06:00
MHDA- 2016/12/15 06:00
PMCR- 2015/12/05
CRDT- 2015/11/28 06:00
PHST- 2015/11/28 06:00 [entrez]
PHST- 2015/11/28 06:00 [pubmed]
PHST- 2016/12/15 06:00 [medline]
PHST- 2015/12/05 00:00 [pmc-release]
AID - ChinMedJ_2015_128_23_3211_170259 [pii]
AID - CMJ-128-3211 [pii]
AID - 10.4103/0366-6999.170259 [doi]
PST - ppublish
SO  - Chin Med J (Engl). 2015 Dec 5;128(23):3211-8. doi: 10.4103/0366-6999.170259.