Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium/calcium exchangers are neuronal plasma membrane transporters, which by coupling Ca2+ and Na+ fluxes, may play a relevant role in brain ischemia. The exchanger gene superfamily comprises two arms: the K+-independent (NCX) and K+-dependent (NCKX) exchangers. In the brain, three different NCX (NCX1, NCX2, NCX3) and three NCKX (NCKX2, NCKX3, NCKX4) family members have been described. Up to now, no sutides about the role played by NCKX proteins in cerebral ischemia have been published. The aim of the present study was to investigate the role of NCKX2 in an in vivo model of permanent middle cerebral artery occlusion (pMCAO). The role of this protein in the development of ischemic damage was assessed by knocking-down its expression with an antisense oligodeoxynucleotide (AS-ODN), intracerebroventricularly infused by an osmotic minipump for 48 h, starting from 24 h before pMCAO. The results showed that NCKX2 knocking-down by using antisense strategy increased the extent of the ischemic lesion. The results of this study suggest that NCKX2 could exert a neuroprotective effect during ischemic injury.
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PMID:Involvement of the potassium-dependent sodium/calcium exchanger gene product NCKX2 in the brain insult induced by permanent focal cerebral ischemia. 1744 91

The superfamily of cation/Ca2+ plasma-membrane exchangers contains two branches, the K+-independent Na+-Ca2+ exchangers (NCXs) and the K+-dependent Na+-Ca2+ exchangers (NCKXs), widely expressed in mammals. NCKX2 is the major neuronally expressed isoform among NCKX members. Despite its importance in maintaining Na+, Ca2+, and K+ homeostasis in the CNS, the role of NCKX2 during cerebral ischemia, a condition characterized by an alteration of ionic concentrations, has not yet been investigated. The present study examines NCKX2 role in the development of ischemic brain damage in permanent middle cerebral artery occlusion (pMCAO) and transient middle cerebral artery occlusion. Furthermore, to evaluate the effect of nckx2 ablation on neuronal survival, nckx2-/- primary cortical neurons were subjected to oxygen glucose deprivation plus reoxygenation. NCKX2 mRNA and protein expression was evaluated in the ischemic core and surrounding ipsilesional areas, at different time points after pMCAO in rats. In ischemic core and in periinfarctual area, NCKX2 mRNA and protein expression were downregulated. In addition, NCKX2 knock-down by antisense oligodeoxynucleotide and NCKX2 knock-out by genetic disruption dramatically increased infarct volume. Accordingly, nckx2-/- primary cortical neurons displayed a higher vulnerability and a greater [Ca2+]i increase under hypoxic conditions, compared with nckx2+/+ neurons. In addition, NCKX currents both in the forward and reverse mode of operation were significantly reduced in nckx2-/- neurons compared with nckx2+/+ cells. Overall, these results indicate that NCKX2 is involved in brain ischemia, and it may represent a new potential target to be investigated in the study of the molecular mechanisms involved in cerebral ischemia.
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PMID:A critical role for the potassium-dependent sodium-calcium exchanger NCKX2 in protection against focal ischemic brain damage. 1830 40