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Activation of apoptosis-linked caspase(s) in NMDA-injured brains in neonatal rats.

机译:新生大鼠NMDA损伤脑中凋亡相关半胱天冬酶的激活。

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摘要

Unilateral injection of 50 nmol of N-methyl-D-aspartate (NMDA) into the left posterior striatum of 7 day-old rat pups induces massive neuronal loss in the ipsilateral hemisphere in 5 days. In this model of excitotoxicity, the form of neuronal death (necrosis vs apoptosis) has not been clearly addressed. Here we report evidence of DNA laddering in the ipsilateral hemisphere 24 h after the NMDA injection. Activation of apoptosis-linked caspase(s) was also identified, as evidenced by (i) the formation of caspase-produced 120 kDa alpha-spectrin breakdown product (SBDP120) and (ii) increase in hydrolysis of caspase-3 substrate acetyl-DEVD-7-amido-4-methylcoumarin in the homogenate from the ipsilateral hemisphere. Lastly, we note that i.p. injection (100 mg/kg) of a pan caspase inhibitor Z-D-DCB attenuates the levels of SBDP120. Our results suggest the presence of caspase-activation in this rat pup model of NMDA toxicity.
机译:向7日龄幼崽的左后纹状体单侧注射50 nmol的N-甲基-D-天冬氨酸(NMDA)在5天内引起同侧半球大量神经元丢失。在这种兴奋性毒性模型中,神经元死亡(坏死与凋亡)的形式尚未明确解决。在这里,我们报告了在NMDA注射后24小时内同侧半球中DNA阶梯化的证据。还证实了凋亡相关的胱天蛋白酶的活化,这由(i)胱天蛋白酶产生的120 kDaα-果胶分解产物(SBDP120)的形成和(ii)胱天蛋白酶3底物乙酰基DEVD水解的增加所证明。来自同侧半球的匀浆中的-7-酰胺基-4-甲基香豆素。最后,我们注意到注射半胱天冬酶抑制剂Z-D-DCB(100 mg / kg)会降低SBDP120的水平。我们的结果表明在该大鼠幼鼠的NMDA毒性模型中存在胱天蛋白酶激活。

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