PMID- 19181966
OWN - NLM
STAT- MEDLINE
DCOM- 20090409
LR  - 20211020
IS  - 0363-6135 (Print)
IS  - 1522-1539 (Electronic)
IS  - 0363-6135 (Linking)
VI  - 296
IP  - 3
DP  - 2009 Mar
TI  - Restoration of contractility in hyperhomocysteinemia by cardiac-specific deletion 
      of NMDA-R1.
PG  - H887-92
LID - 10.1152/ajpheart.00750.2008 [doi]
AB  - Homocysteine (HCY) activated mitochondrial matrix metalloproteinase-9 and led to 
      cardiomyocyte dysfunction, in part, by inducing mitochondrial permeability (MPT). 
      Treatment with MK-801 [N-methyl-d-aspartate (NMDA) receptor antagonist] 
      ameliorated the HCY-induced decrease in myocyte contractility. However, the role 
      of cardiomyocyte NMDA-receptor 1 (R1) activation in hyperhomocysteinemia (HHCY) 
      leading to myocyte dysfunction was not well understood. We tested the hypothesis 
      that the cardiac-specific deletion of NMDA-R1 mitigated the HCY-induced decrease 
      in myocyte contraction, in part, by decreasing nitric oxide (NO). 
      Cardiomyocyte-specific knockout of NMDA-R1 was generated using cre/lox 
      technology. NMDA-R1 expression was detected by Western blot and confocal 
      microscopy. MPT was determined using a spectrophotometer. Myocyte contractility 
      and calcium transients were studied using the IonOptix video-edge detection 
      system and fura 2-AM loading. We observed that HHCY induced NO production by 
      agonizing NMDA-R1. HHCY induced the MPT by agonizing NMDA-R1. HHCY caused a 
      decrease in myocyte contractile performance, maximal rate of contraction and 
      relaxation, and prolonged the time to 90% peak shortening and 90% relaxation by 
      agonizing NMDA-R1. HHCY decreased contraction amplitude with the increase in 
      calcium concentration. The recovery of calcium transient was prolonged in HHCY 
      mouse myocyte by agonizing NMDA-R1. It was suggested that HHCY increased 
      mitochondrial NO levels and induced MPT, leading to the decline in myocyte 
      mechanical function by agonizing NMDA-R1.
FAU - Moshal, Karni S
AU  - Moshal KS
AD  - Dept. of Physiology and Biophysics, 500 S. Preston St., HSC Bldg. A-1115, Univ. 
      of Louisville, Louisville, KY 40202, USA.
FAU - Kumar, Munish
AU  - Kumar M
FAU - Tyagi, Neetu
AU  - Tyagi N
FAU - Mishra, Paras K
AU  - Mishra PK
FAU - Metreveli, Naira
AU  - Metreveli N
FAU - Rodriguez, Walter E
AU  - Rodriguez WE
FAU - Tyagi, Suresh C
AU  - Tyagi SC
LA  - eng
GR  - HL-71010/HL/NHLBI NIH HHS/United States
GR  - HL-74185/HL/NHLBI NIH HHS/United States
GR  - HL-88012/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090130
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Mitochondrial Membrane Transport Proteins)
RN  - 0 (Mitochondrial Permeability Transition Pore)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Animals
MH  - Calcium Signaling
MH  - Disease Models, Animal
MH  - Hyperhomocysteinemia/metabolism/*physiopathology
MH  - Mice
MH  - Mice, Knockout
MH  - Mitochondria, Heart/metabolism
MH  - Mitochondrial Membrane Transport Proteins/metabolism
MH  - Mitochondrial Permeability Transition Pore
MH  - *Myocardial Contraction
MH  - Myocytes, Cardiac/*metabolism
MH  - Nitric Oxide/metabolism
MH  - Oxidative Stress
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, N-Methyl-D-Aspartate/*deficiency/genetics
PMC - PMC2660230
EDAT- 2009/02/03 09:00
MHDA- 2009/04/10 09:00
PMCR- 2010/03/01
CRDT- 2009/02/03 09:00
PHST- 2009/02/03 09:00 [entrez]
PHST- 2009/02/03 09:00 [pubmed]
PHST- 2009/04/10 09:00 [medline]
PHST- 2010/03/01 00:00 [pmc-release]
AID - 00750.2008 [pii]
AID - H-00750-2008 [pii]
AID - 10.1152/ajpheart.00750.2008 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2009 Mar;296(3):H887-92. doi: 
      10.1152/ajpheart.00750.2008. Epub 2009 Jan 30.