PMID- 24057865
OWN - NLM
STAT- MEDLINE
DCOM- 20140623
LR  - 20211203
IS  - 1940-4034 (Electronic)
IS  - 1074-2484 (Linking)
VI  - 18
IP  - 6
DP  - 2013 Nov
TI  - Combination of D942 with curcumin protects cardiomyocytes from ischemic damage 
      through promoting autophagy.
PG  - 570-81
LID - 10.1177/1074248413503495 [doi]
AB  - Myocardial ischemia is one of the main causes of sudden cardiac death. Autophagy 
      has been demonstrated to protect cardiomyocytes from ischemia/reperfusion 
      (I/R)-induced damage. A small molecule compound 
      5-(3-(4-(2-(4-fluorophenyl)ethoxy)phenyl)propyl)furan-2-carboxylic acid (D942) 
      has been previously shown to specifically activate adenosine 
      monophosphate-activated protein kinase (AMPK) in cancer cells. Another reagent, 
      curcumin, has been shown to inhibit mammalian target of rapamycin (mTOR) signal 
      pathway in tumor cells. Since AMPK signaling induces autophagy, while mTOR 
      signaling inhibits autophagy, here we tested the potential protective efficacy of 
      D942 with curcumin for cardiomyocytes under oxygen-glucose deprivation and 
      reoxygenation (OGD/R). Mouse neonatal cardiomyocytes were treated with D942 and 
      curcumin after being subjected to OGD/R. Cell survival and autophagy-related 
      signal pathways were measured after treatment. Our data indicated both D942 and 
      curcumin enhanced cell survival after OGD/R. The D942 and curcumin induced 
      autophagy in cardiomyocytes through activating AMPK pathway or inhibiting mTOR 
      signaling. Induction of autophagy by D942 and curcumin was the cause of 
      cardioprotection, since inhibition of autophagy abolished the protective 
      efficacy. Furthermore, combination treatment with D942 and curcumin profoundly 
      upregulated autophagy after OGD/R and significantly promoted cell survival. 
      Treatment with D942 and curcumin significantly upregulated autophagy in a murine 
      myocardial I/R model. Taken together, our research suggests that D942 and 
      curcumin could be promising therapeutic agents for myocardial I/R.
FAU - Yang, Keping
AU  - Yang K
AD  - 1Department of Cardiology, Renmin Hospital of Wuhan University, Institute of 
      Cardiovascular Diseases, Wuhan, China.
FAU - Xu, Chenhong
AU  - Xu C
FAU - Li, Xin
AU  - Li X
FAU - Jiang, Hong
AU  - Jiang H
LA  - eng
PT  - Journal Article
DEP - 20130919
PL  - United States
TA  - J Cardiovasc Pharmacol Ther
JT  - Journal of cardiovascular pharmacology and therapeutics
JID - 9602617
RN  - 0 (Carboxylic Acids)
RN  - 0 (D942 compound)
RN  - 0 (Furans)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.31 (AMP-Activated Protein Kinases)
RN  - IT942ZTH98 (Curcumin)
SB  - IM
MH  - AMP-Activated Protein Kinases/metabolism
MH  - Animals
MH  - Animals, Newborn
MH  - Autophagy/drug effects
MH  - Carboxylic Acids/administration & dosage/*pharmacology
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Curcumin/administration & dosage/*pharmacology
MH  - Disease Models, Animal
MH  - Drug Therapy, Combination
MH  - Furans/administration & dosage/*pharmacology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Myocardial Reperfusion Injury/complications/*drug therapy
MH  - Myocytes, Cardiac/*drug effects/pathology
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - autophagy
OT  - cardiomyocyte
OT  - curcumin
OT  - ischemia
EDAT- 2013/09/24 06:00
MHDA- 2014/06/24 06:00
CRDT- 2013/09/24 06:00
PHST- 2013/09/24 06:00 [entrez]
PHST- 2013/09/24 06:00 [pubmed]
PHST- 2014/06/24 06:00 [medline]
AID - 1074248413503495 [pii]
AID - 10.1177/1074248413503495 [doi]
PST - ppublish
SO  - J Cardiovasc Pharmacol Ther. 2013 Nov;18(6):570-81. doi: 
      10.1177/1074248413503495. Epub 2013 Sep 19.