PMID- 28713934
OWN - NLM
STAT- MEDLINE
DCOM- 20180424
LR  - 20211204
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 16
IP  - 3
DP  - 2017 Sep
TI  - Upregulation of connexin 43 and apoptosis‑associated protein expression by high 
      glucose in H9c2 cells was improved by resveratrol via the autophagy signaling 
      pathway.
PG  - 3262-3268
LID - 10.3892/mmr.2017.6953 [doi]
AB  - The expression of connexin43 (Cx43) protein and the apoptotic rate of 
      cardiomyocytes may be regulated by autophagy and associated with diabetic 
      cardiomyopathy. It is possible that the beneficial effect of resveratrol on 
      diabetic cardiomyocytes occurs via the autophagy pathway. However, it remains to 
      be elucidated whether resveratrol treatment may attenuate the 
      hyperglycemia‑induced remodeling of Cx43 and apoptosis through the regulation of 
      autophagy. H9c2 cardiac cells were incubated with 5.5 and 25 mM glucose, 25 mM 
      glucose with chloroquine (50 microM), and 25 mM glucose with or without resveratrol 
      (10, 25 microM) for 24 h. H9c2 cells were also incubated with 25 microM resveratrol in 
      the presence of chloroquine (50 microM). Cell viability was determined using an MTT 
      cell survival assay. Cytotoxicity was determined by quantification of the release 
      of lactate dehydrogenase. The expression of Cx43, autophagic maker proteins 
      [Beclin‑1, p62 and microtubule‑associated protein 1 light chain 3 (LC3)], 
      apoptosis maker proteins (B‑cell lymphoma‑2 and Bcl‑2 associated X protein), 
      AMP‑activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) were 
      determined using western blotting. Resveratrol treatment led to reduced Cx43 
      expression levels compared with the 25 mM glucose treatment and significantly 
      reduced the expression of apoptosis‑associated proteins in H9c2 cells under 
      hyperglycemic conditions. Autophagy was increased as indicated by the 
      upregulation of Beclin‑1 and p62 expression and the reduced LC3‑II/LC3‑I ratio. 
      AMPK expression was increased, whereas mTOR expression was reduced in the 
      resveratrol treatment groups. Treatment with chloroquine reversed effect of 
      resveratrol. In conclusion, administration resveratrol may protect H9c2 cells 
      against hyperglycemia‑induced Cx43 upregulation and apoptosis, which may be 
      mediated through the induction of the autophagy signaling pathway.
FAU - Wang, Guang-Yu
AU  - Wang GY
AD  - Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200233, P.R. China.
FAU - Bi, Ya-Guang
AU  - Bi YG
AD  - Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200233, P.R. China.
FAU - Liu, Xiang-Dong
AU  - Liu XD
AD  - Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200233, P.R. China.
FAU - Han, Jun-Feng
AU  - Han JF
AD  - Department of Endocrinology and Metabolism, Shanghai Sixth People's Hospital, 
      Shanghai Jiao Tong University, Shanghai 200233, P.R. China.
FAU - Wei, Meng
AU  - Wei M
AD  - Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200233, P.R. China.
FAU - Zhang, Qing-Yong
AU  - Zhang QY
AD  - Department of Cardiology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong 
      University, Shanghai 200233, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20170712
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Connexin 43)
RN  - 0 (Stilbenes)
RN  - 886U3H6UFF (Chloroquine)
RN  - EC 1.1.1.27 (L-Lactate Dehydrogenase)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
RN  - Q369O8926L (Resveratrol)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Chloroquine/pharmacology
MH  - Connexin 43/*metabolism
MH  - Down-Regulation/drug effects
MH  - Glucose/*toxicity
MH  - Hyperglycemia/pathology
MH  - L-Lactate Dehydrogenase/metabolism
MH  - Mice
MH  - Resveratrol
MH  - Signal Transduction/*drug effects
MH  - Stilbenes/*pharmacology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Up-Regulation/*drug effects
PMC - PMC5547968
EDAT- 2017/07/18 06:00
MHDA- 2018/04/25 06:00
PMCR- 2017/07/12
CRDT- 2017/07/18 06:00
PHST- 2016/04/22 00:00 [received]
PHST- 2017/05/05 00:00 [accepted]
PHST- 2017/07/18 06:00 [pubmed]
PHST- 2018/04/25 06:00 [medline]
PHST- 2017/07/18 06:00 [entrez]
PHST- 2017/07/12 00:00 [pmc-release]
AID - mmr-16-03-3262 [pii]
AID - 10.3892/mmr.2017.6953 [doi]
PST - ppublish
SO  - Mol Med Rep. 2017 Sep;16(3):3262-3268. doi: 10.3892/mmr.2017.6953. Epub 2017 Jul 
      12.