Glycine protects cardiomyocytes against lethal reoxygenation injury by inhibiting mitochondrial permeability transition.
Post-ischaemic reperfusion may precipitate cardiomyocyte death upon correction of intracellular acidosis due in part to mitochondrial permeability transition. We investigated whether glycine, an amino acid with poorly understood cytoprotective properties, may interfere with this mechanism. In cardiomyocyte cultures, addition of glycine during re-energization following 1 h of simulated ischaemia (NaCN/2-deoxyglucose, pH 6.4) completely prevented necrotic cell death associated with pH normalization. Glycine also protected against cell death associated with pH normalization in reoxygenated rat hearts. Glycine prevented cyclosporin-sensitive swelling and calcein release associated with re-energization in rat heart mitochondria submitted to simulated ischaemia or to Ca(2+) stress under normoxia. NMR spectroscopy revealed a marked glycine depletion in re-energized cardiomyocytes that was reversed by exposure to 3 mm glycine. These results suggest that intracellular glycine exerts a previously unrecognized inhibition on mitochondrial permeability transition in cardiac myocytes, and that intracellular glycine depletion during myocardial hypoxia/reoxygenation makes the cell more vulnerable to necrotic death.
Ruiz-Meana
Marisol
M
Unidad de Investigacion B, Hospital Universitario Vall d'Hebron, Pg. Vall d'Hebron 119-129, 08035 Barcelona, Spain. dgdorado@vhebron.net
Pina
Pilar
P
Garcia-Dorado
David
D
Rodríguez-Sinovas
Antonio
A
Barba
Ignasi
I
Miró-Casas
Elisabet
E
Mirabet
Maribel
M
Soler-Soler
Jordi
J
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D005998:Glycine / Q000494:pharmacology*; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D010100:Oxygen; D005998:Glycine