We investigated the expression of Na(+)/Ca(2+) exchanger (NCX) and the functional role of NCX in retinal damage by using NCX1-heterozygous deficient mice (NCX1(+/-)) and SEA0400 (2-[4-[(2,5-difluorophenyl)methoxy] phenoxy]-5-ethoxyaniline), a selective NCX inhibitor in vivo. We also examined the role of NCX in oxygen-glucose deprivation (OGD) stress with a retinal ganglion cell line (RGC-5) cell culture in vitro. The expression of NCX1 was confirmed and entirely localized in retina by immunoblotting and immunohistochemistry, respectively. NCX1(+/-) mice possessed significant protection against retinal damage induced by intravitreal injection of N-methyl-D-aspartate (NMDA). SEA0400 at 3 and 10 mg/kg significantly reduced NMDA- or high intraocular pressure-induced retinal cell damage in mice. Furthermore, SEA0400 reduced the number of TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling)-positive cells and the expression of phosphorylated mitogen-activated protein kinases (ERK1/2, JNK, p38) induced by NMDA injection. In RGC-5, SEA0400 at 0.3 and 1 microM significantly inhibited OGD-induced cell damage. OGD-induced cell damage was aggravated by ouabain (a Na(+),K(+)-ATPase inhibitor) at 100 microM, and this increased damage was significantly reduced by SEA0400 at 1 microM. In conclusion, these results suggest that NCX1 may play a role in retinal cell death induced by NMDA and ischemia-reperfusion.
We investigated the expression of Na(+)/Ca(2 + ) exchanger ( NCX ) and the functional role of NCX in retinal damage by using NCX1-heterozygous deficient mice ( NCX1(+/- ) ) and SEA0400 ( 2-[4-[(2,5-difluorophenyl)methoxy ] phenoxy]-5-ethoxyaniline ) , a selective NCX inhibitor in vivo . We also examined the role of NCX in oxygen - glucose deprivation ( OGD ) stress with a retinal ganglion cell line ( RGC-5 ) cell culture in vitro . The expression of NCX1 was confirmed and entirely localized in retina by immunoblotting and immunohistochemistry , respectively . NCX1(+/- ) mice possessed significant protection against retinal damage induced by intravitreal injection of N - methyl - D - aspartate ( NMDA ) . SEA0400 at 3 and 10 mg / kg significantly reduced NMDA- or high intraocular pressure - induced retinal cell damage in mice . Furthermore , SEA0400 reduced the number of TUNEL ( terminal deoxynucleotidyl transferase dUTP nick - end labeling)-positive cells and the expression of phosphorylated mitogen - activated protein kinases ( ERK1/2 , JNK , p38 ) induced by NMDA injection . In RGC-5 , SEA0400 at 0.3 and 1 microM significantly inhibited OGD - induced cell damage . OGD - induced cell damage was aggravated by ouabain ( a Na(+),K(+)-ATPase inhibitor ) at 100 microM , and this increased damage was significantly reduced by SEA0400 at 1 microM. In conclusion , these results suggest that NCX1 may play a role in retinal cell death induced by NMDA and ischemia - reperfusion .
The small molecule SEA0400 is an inhibitor of which ion antiporter/exchanger?
The small molecule SEA0400 is an inhibitor of which ion antiporter / exchanger ?
Na(+)/Ca(2+) exchanger NCX
Na(+)/Ca(2+) exchanger NCX