PMID- 16925458
OWN - NLM
STAT- MEDLINE
DCOM- 20080214
LR  - 20211006
IS  - 0862-8408 (Print)
IS  - 0862-8408 (Linking)
VI  - 56
IP  - 5
DP  - 2007
TI  - NMDA receptor activation induces mitochondrial dysfunction, oxidative stress and 
      apoptosis in cultured neonatal rat cardiomyocytes.
PG  - 559-569
AB  - Glutamate is a well-characterized excitatory neurotransmitter in the central 
      nervous system (CNS). Recently, glutamate receptors (GluRs) were also found in 
      peripheral tissues, including the heart. However, the function of GluRs in 
      peripheral organs remains poorly understood. In the present study, we found that 
      N-methyl-D-aspartate (NMDA) could increase intracellular calcium ([Ca(2+)]i) 
      level in a dose-dependent manner in cultured neonatal rat cardiomyocytes. NMDA at 
      10(-4) M increased the levels of reactive oxygen species (ROS), cytosolic 
      cytochrome c (cyto c), and 17-kDa caspase-3, but depolarized mitochondrial 
      membrane potential, leading to cardiomyocyte apoptosis. In addition, NMDA 
      treatment induced an increase in bax mRNA but a decrease in bcl-2 mRNA expression 
      in the cardiomyocytes. The above effects of NMDA were blocked by the NMDA 
      receptor antagonist 
      (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate 
      (MK-801), and by ROS scavengers glutathione (GSH) and N-acetylcystein (NAC). 
      These results suggest that stimulation of NMDA receptor in the cardiomyocyte may 
      lead to apoptosis via a Ca(2+), ROS, and caspase-3 mediated pathway. These 
      findings suggest that NMDA receptor may play an important role in myocardial 
      pathogenesis.
FAU - Gao, X
AU  - Gao X
AD  - Department of Physiology, School of Basic Medicine, Peking Union Medical College, 
      Beijing, China.
FAU - Xu, X
AU  - Xu X
FAU - Pang, J
AU  - Pang J
FAU - Zhang, C
AU  - Zhang C
FAU - Ding, J M
AU  - Ding JM
FAU - Peng, X
AU  - Peng X
FAU - Liu, Y
AU  - Liu Y
FAU - Cao, J M
AU  - Cao JM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060822
PL  - Czech Republic
TA  - Physiol Res
JT  - Physiological research
JID - 9112413
RN  - 0 (Antioxidants)
RN  - 0 (Bax protein, rat)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (RNA, Messenger)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - 6LR8C1B66Q (Dizocilpine Maleate)
RN  - 9007-43-6 (Cytochromes c)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
RN  - GAN16C9B8O (Glutathione)
RN  - SY7Q814VUP (Calcium)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/pharmacology
MH  - Animals
MH  - Animals, Newborn
MH  - Antioxidants/pharmacology
MH  - Apoptosis/*drug effects
MH  - Calcium/metabolism
MH  - Caspase 3/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Cytochromes c/metabolism
MH  - Dizocilpine Maleate/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Enzyme Activation
MH  - Excitatory Amino Acid Agonists/*pharmacology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Glutathione/metabolism
MH  - Membrane Potential, Mitochondrial/drug effects
MH  - Mitochondria, Heart/*drug effects/metabolism/pathology
MH  - Myocytes, Cardiac/*drug effects/metabolism/pathology
MH  - N-Methylaspartate/*pharmacology
MH  - Oxidative Stress/*drug effects
MH  - Proto-Oncogene Proteins c-bcl-2/genetics/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*agonists/antagonists & inhibitors/metabolism
MH  - Time Factors
MH  - bcl-2-Associated X Protein/genetics/metabolism
EDAT- 2006/08/24 09:00
MHDA- 2008/02/15 09:00
CRDT- 2006/08/24 09:00
PHST- 2006/08/24 09:00 [pubmed]
PHST- 2008/02/15 09:00 [medline]
PHST- 2006/08/24 09:00 [entrez]
AID - 1053 [pii]
AID - 10.33549/physiolres.931053 [doi]
PST - ppublish
SO  - Physiol Res. 2007;56(5):559-569. doi: 10.33549/physiolres.931053. Epub 2006 Aug 
      22.