PMID- 30847932
OWN - NLM
STAT- MEDLINE
DCOM- 20200526
LR  - 20200526
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 234
IP  - 10
DP  - 2019 Aug
TI  - Theaflavin 3,3'-digallate reverses the downregulation of connexin 43 and 
      autophagy induced by high glucose via AMPK activation in cardiomyocytes.
PG  - 17999-18016
LID - 10.1002/jcp.28432 [doi]
AB  - Theaflavin 3,3'-digallate (TF3), is reported to protect cardiomyocytes from 
      lipotoxicity and reperfusion injury. However, the role of TF3 in the protection 
      of high-glucose injury is still poorly understood. This study investigated the 
      protective effects of TF3 on gap junctions and autophagy in neonatal 
      cardiomyocytes (NRCMs). NRCMs preincubated with high glucose were coincubated 
      with TF3. The expression of connexins and autophagy-related proteins was 
      determined. The functioning of gap-junctional intercellular communication (GJIC) 
      was measured by a dye transfer assay. Adenosine monophosphate-activated protein 
      kinase (AMPK) activity was determined by western blot. Moreover, AMPK was 
      activated with aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) or 
      inhibited by AMPKalpha small interfering RNA (siRNA) to explore the role of AMPK in 
      the modulation of connexin 43 (Cx43) and autophagy. Meanwhile, autophagy was 
      activated or blocked to observe the change in Cx43 expression. It was found that 
      the protein expression of Cx43 and autophagy-related proteins was increased in a 
      TF3 dose- and time-dependent manner under high glucose. TF3 also recovered the 
      reduced GJIC function induced by high glucose concentrations. TF3 activated 
      phosphorylated AMPK in a time-dependent way. AMPKalpha siRNA abrogated the protection 
      of TF3, while AICAR showed similar results compared to the TF3 treatment. 
      Meanwhile, autophagy activation caused decreased Cx43, while cotreatment with baf 
      A1 enhanced Cx43 expression further compared with the TF3 treatment alone under 
      high glucose. We concluded that TF3 partly reversed the inhibition of Cx43 
      expression and autophagy induced by high glucose in NRCMs, partly by restoring 
      AMPK activity. Inhibition of autophagy might be protective by preserving Cx43 
      expression in NRCMs stimulated by high glucose.
CI  - (c) 2019 Wiley Periodicals, Inc.
FAU - Shen, Zhida
AU  - Shen Z
AUID- ORCID: 0000-0001-7068-8689
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Chen, Qi
AU  - Chen Q
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Jin, Tingting
AU  - Jin T
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Wang, Meihui
AU  - Wang M
AD  - Department of Cardiology Basic Research, Biomedical Research Center, Sir Run Run 
      Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
FAU - Ying, Hangying
AU  - Ying H
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Lu, Jiangting
AU  - Lu J
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Wang, Ming
AU  - Wang M
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Zhang, Wenbin
AU  - Zhang W
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Qiu, Fuyu
AU  - Qiu F
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Jin, Chongying
AU  - Jin C
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Zhao, Yanbo
AU  - Zhao Y
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
FAU - Fu, Guosheng
AU  - Fu G
AD  - Department of Cardiology, Sir Run Run Shaw Hospital, Zhejiang University School 
      of Medicine, Hangzhou, Zhejiang, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20190307
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Biflavonoids)
RN  - 0 (Connexin 43)
RN  - 0 (Gja1 protein, rat)
RN  - 0 (theaflavin-3,3'-digallate)
RN  - 8R1V1STN48 (Catechin)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - AMP-Activated Protein Kinases/genetics/*metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Autophagy/*drug effects
MH  - Biflavonoids/*pharmacology
MH  - Cardiotoxicity
MH  - Catechin/*analogs & derivatives/pharmacology
MH  - Cells, Cultured
MH  - Connexin 43/genetics/*metabolism
MH  - Enzyme Activation
MH  - Gap Junctions/drug effects/metabolism/pathology
MH  - Glucose/*toxicity
MH  - Myocytes, Cardiac/*drug effects/enzymology/pathology
MH  - Rats, Sprague-Dawley
MH  - Signal Transduction
OTO - NOTNLM
OT  - 3'-digallate
OT  - AMPK
OT  - Cx43
OT  - autophagy
OT  - cardiomyocytes
OT  - theaflavin 3
EDAT- 2019/03/09 06:00
MHDA- 2020/05/27 06:00
CRDT- 2019/03/09 06:00
PHST- 2018/11/25 00:00 [received]
PHST- 2019/02/03 00:00 [revised]
PHST- 2019/02/14 00:00 [accepted]
PHST- 2019/03/09 06:00 [pubmed]
PHST- 2020/05/27 06:00 [medline]
PHST- 2019/03/09 06:00 [entrez]
AID - 10.1002/jcp.28432 [doi]
PST - ppublish
SO  - J Cell Physiol. 2019 Aug;234(10):17999-18016. doi: 10.1002/jcp.28432. Epub 2019 
      Mar 7.