Arandarcikaite 2013 Abstract MiP2013

Arandarcikaite O, Borutaite V (2013) The protective effect of NO against ischemia induced brain mitochondrial injury. Mitochondr Physiol Network 18.08.

Link:

Arandarcikaite O, Borutaite V (2013)

Event: MiP2013

Our research group has previously reported that NO can protect heart mitochondria from ischemia-induced mitochondrial permeability transition pore-related release of cytochrome c and subsequent cell death [1]. In this study we sought to determine whether preconditioning with NO can decrease brain mitochondrial sensitivity to calcium and protect against ischemia-induced mitochondrial damages as mediated by activation of protein kinase G.

Nitric oxide donor (NOC-18) (50 µM) was infused into the vena cava for 5 min and induced ischemia by keeping isolated brain in a hypoxic chamber for 90 min. To test if the protective effect of NO on brain mitochondria during 90 min ischemia was due to PKG activation before inducing ischemia in vena cava, we infused the PKG inhibitor KT5823 (1 µM) and NOC-18.

We found that preconditioning of the brain with NO donor increased the resistance of subsequently isolated mitochondria to calcium-induced opening of the mitochondrial permeability transition pore (PTP). This was assayed by measuring the extramitochondrial Ca2+ concentration with Calcium Green-5N. In mitochondria isolated from ischemic brain pre-treated with NO, 44% more calcium was necessary to cause PTP opening compared to ischemic brain mitochondria. Pre-treatment of brain in the ischemic group with PKG inhibitor and NO donor resulted in no statistically significant differences to controls. Similarly, pre-treatment with NO had no effect on mitochondrial respiration.

Ischemia-induced release of lactate dehydrogenase (LDH) indicates that cells died by necrosis. Pre-treatment of brain with NOC-18 abolished LDH release by 33% compared to ischemia. KT5823 applied together with NOC-18 restored necrosis back to a level similar to that induced by ischemia without NOC-18, indicating that PKG mediates the protective action of NOC-18.

These findings suggest that NO increases mitochondria sensitivity to calcium ions and protects brain mitochondria from ischemia induced PTP and necrotic cell death in a PKG depending manner.

• O2k-Network Lab: LT Kaunas Borutaite V

Labels:

Stress:Ischemia-Reperfusion; Preservation"Ischemia-Reperfusion; Preservation" is not in the list (Cell death, Cryopreservation, Ischemia-reperfusion, Permeability transition, Oxidative stress;RONS, Temperature, Hypoxia, Mitochondrial disease) of allowed values for the "Stress" property. 

Tissue;cell: Nervous system  Preparation: Isolated Mitochondria"Isolated Mitochondria" is not in the list (Intact organism, Intact organ, Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, SMP, Chloroplasts, Enzyme, Oxidase;biochemical oxidation, ...) of allowed values for the "Preparation" property. 

Calcium, NO 

Affiliations and author contributions

Lithuanian University of Health Sciences, Institute of Neurosciences, Kaunas, Lithuania.

Email: [email protected]

References

1. Borutaitė V, Morkūnienė R, Arandarčikaitė O, Jekabsonė A, Barauskaitė J, Brown GC (2009) Nitric oxide protects the heart from ischemia-induced apoptosis and mitochondrial damage via protein kinase G mediated blockage of permeability transition and cytochrome c release. J Biomed Sci 11: 16-70.