Details

Autor(en) / Beteiligte

• LUO, JING
• WANG, YANPING
• CHEN, XINZHI
• CHEN, HAI
• KINTNER, DOUGLAS B.
• SHULL, GARY E.
• PHILIPSON, KENNETH D.
• SUN, DANDAN

Titel

Increased Tolerance to Ischemic Neuronal Damage by Knockdown of Na+-Ca2+ Exchanger Isoform 1

Ist Teil von

• Annals of the New York Academy of Sciences, 2007-03, Vol.1099 (1), p.292-305

Ort / Verlag

Malden, USA: Blackwell Publishing Inc

Erscheinungsjahr

2007

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• :  We hypothesize that stimulation of Na+–K+–Cl+ cotransporter (NKCC1) causes Na+ overload that may lead to reversal of Na+–Ca2+ exchanger isoform 1 (NCX1) and ischemic neuronal damage. NCX1 protein expression and Ca2+ influx via reversal of NCX were decreased by ∼70% in NCX1+/− neurons. Compared to NCX1+/+ neurons, NCX1+/− neurons exhibited significantly less cell death (∼30%) after 3 h oxygen and glucose deprivation (OGD) and 21 h reoxygenation. Additional neuroprotection was found in NCX1+/− neurons treated with NCX inhibitor KB‐R7943. Moreover, expression of NCX1 protein was ∼40% lower in NCX1+/− brains than in NCX1+/+ brains. However, there was no significant reduction in cerebral infarction in NCX1+/− mice following middle cerebral artery occlusion (MCAO). These data suggest that moderate reduction of NCX1 protein may be not enough to exert protection. We used small RNA‐interference (siRNA) approach to further elucidate the role of NCX1 in ischemic cell damage. Efficacy of anti‐NCX1 siRNA was tested in astrocytes and ∼50% knockdown of NCX1 protein expression was achieved after 24–72 h transfection. Reduction in NCX1 protein expression was also found in brains of NCX1+/− mice after the siRNA injection. NCX1+/− mice treated with siRNA showed ∼20% less MCAO‐induced infarction, compared to NCX1+/− mice. Approximately 50% neuroprotection was detected in NKCC1+/−/NCX1+/− mice following MCAO. In conclusion, these data suggest that NCX1 plays an important role in ischemia/reperfusion‐induced neuronal injury.