Ginkgo biloba extract (EGb 761) protects Na,K-ATPase isoenzymes during cerebral ischemia.
Disturbances of Na,K-ATPase activity are implicated in the pathophysiology of cerebral ischemia. Previous experiments have shown that EGb 761 protects NaK-ATPase activity against one hour of cerebral ischemia. In the brain however, the 3 isoenzymes responsible for Na,K-ATPase activity may be differentially affected by various times of ischemia. In the present study, we investigated the effect of a longer period of ischemia, and the protection provided by a pre-treatment with EGb 761 on each of the 3 cerebral NaK-ATPase isoenzymes. In control and EGb 761 pre-treated mice exposed to a 6 hr unilateral occlusion of the middle cerebral artery, Na,K-ATPase activity was decreased by 60% and lipid peroxidation was increased by 40% in the ipsilateral (ischemic) cortex compared to the contralateral one. In parallel, membrane integrity was altered. The alteration of NaK-ATPase activity, as a whole, resulted from a decrease in the activity of the 3 isoenzymes. The two isoenzymes of high ouabain affinity however, had their affinities decreased while the sensitivity of the lowest affinity isoenzyme was increased. Pre-treatment with EGb 761 abolished the differences observed between ipsi- and contralateral cortex, with the exception of the change in ouabain affinity of the low affinity isoenzyme. Ischemia also induced changes in Na,K-ATPase isoenzyme ouabain affinities in the contralateral cortex that where not prevented by EGb 761.
Pierre
Sandrine
S
Laboratoire de Recherche Cardiologique, Université de la Méditerranée, Faculté de Médecine, IFR Jean-Roche, Marseille, France. sandrine.pierre@ttuhsc.edu
Jamme
Isabelle
I
Robert
Karine
K
Gerbi
Alain
A
Duran
Marie-Josée
MJ
Sennoune
Souad
S
Droy-Lefaix
Marie-Thérèse
MT
Nouvelot
André
A
Maixent
Jean-Michel
JM
D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D002540:Cerebral Cortex / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020441:Ginkgo biloba; D007527:Isoenzymes / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008861:Microsomes / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D010936:Plant Extracts / Q000494:pharmacology*; D011485:Protein Binding / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects* / Q000378:metabolism; D000096983:Ginkgo Extract
D004791:Enzyme Inhibitors; D007527:Isoenzymes; D018696:Neuroprotective Agents; D010042:Ouabain; D010936:Plant Extracts; D000254:Sodium-Potassium-Exchanging ATPase; C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract