FACULTY OF MEDICINE, DIVISION OF PHARMACOLOGY SCHOOL IN MOLECULAR MEDICINE PhD PROGRAM IN NEUROSCIENCE XXIV CYCLE “MOLECULAR MECHANISMS OF NCX1 AND NCX3-INDUCED NEUROPROTECTION IN ANOXIC BRAIN PRECONDITIONOING”
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The two isoforms of the Na+/Ca2+ exchanger, NCX1 and NCX3, constitute novel additional targets for the prosurvival action of Akt/protein kinase B pathway.
The proteins NCX1, NCX2, and NCX3 expressed on the plasma membrane of neurons play a crucial role in ionic regulation because they are the major bidirectional system promoting the efflux and influx of Na(+) and Ca(2+) ions. Here, we demonstrate that NCX1 and NCX3 proteins are novel additional targets for the survival action of the phosphatidylinositol 3-kinase (PI3-K)/Akt pathway. Indeed, the d...
متن کاملYM-244769, a novel Na+/Ca2+ exchange inhibitor that preferentially inhibits NCX3, efficiently protects against hypoxia/reoxygenation-induced SH-SY5Y neuronal cell damage.
We investigated the pharmacological properties and interaction domains of N-(3-aminobenzyl)-6-{4-[(3-fluorobenzyl)oxy]phenoxy} nicotinamide (YM-244769), a novel potent Na(+)/Ca(2+) exchange (NCX) inhibitor, using various NCX-transfectants and neuronal and renal cell lines. YM-244769 preferentially inhibited intracellular Na(+)-dependent (45)Ca(2+) uptake via NCX3 (IC(50) = 18 nM); the inhibitio...
متن کاملModulation of Na+-Ca2+ exchanger expression by immunosuppressive drugs is isoform-specific.
The Na(+)-Ca(2+) exchanger (NCX) is a major Ca(2+)-regulating protein encoded by three genes: NCX1, NCX2, and NCX3. They share a sequence homology of approximately 65%. NCX1 protein is expressed ubiquitously, and NCX2 and NCX3 are expressed almost exclusively in the brain. We have shown previously (Kimchi-Sarfaty et al., 2002) that treatment of NCX1-transfected human embryonic kidney (HEK) 293 ...
متن کاملNitric oxide stimulates NCX1 and NCX2 but inhibits NCX3 isoform by three distinct molecular determinants.
In this study, the role of nitric oxide (NO) in the modulation of the activity of NCX1, NCX2, and NCX3 exchangers was investigated in baby hamster kidney cells singly transfected with each of these isoforms by single-cell Fura-2-microfluorometry and patch clamp. Furthermore, the molecular determinants of NO on each isoform were identified by deletion, site-directed mutagenesis, and chimera stra...
متن کاملTwo sodium/calcium exchanger gene products, NCX1 and NCX3, play a major role in the development of permanent focal cerebral ischemia.
BACKGROUND AND PURPOSE The Na+/Ca2+ exchanger, by mediating Ca2+ and Na+ fluxes in a bidirectional way across the synaptic plasma membrane, may play a pivotal role in the events leading to anoxic damage. In the brain, there are 3 different genes coding for 3 different proteins: NCX1, NCX2, and NCX3. The aim of this study was to determine whether NCX1, NCX2, and NCX3 might play a differential ro...
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تاریخ انتشار 2011