Tomimoto H, Takemoto O, Akiguchi I, Yanagihara T
Department of Neurology, Mayo Clinic and Mayo Foundation, Rochester, MN 55905, USA.
Acta Neuropathol. 1999 Jan;97(1):22-30. doi: 10.1007/s004010050951.
The neuroprotective role of the expression of heat shock protein (HSP) and immediate early gene remains unclear. Using immunoelectron microscopy, we examined the ultrastructural integrity of the neurons with expression of c-Fos, c-Jun and HSP70 in gerbils after transient cerebral ischemia and reperfusion. Induction of c-Fos and c-Jun was observed in the CA3 region resistant to ischemia, while HSP70 was expressed not only in the CA3 but also in the vulnerable CAI region. With immunoelectron microscopy, the expression of c-Fos/c-Jun and HSP70 was observed in the neurons which retained neuronal integrity except for mitochondrial swelling and polyribosomal disaggregation. In contrast, the CAI neurons without immunoreaction for HSP70 showed cytoplasmic vacuoles and parallel stacking of rough endoplasmic reticulum, the features associated with the process of delayed neuronal death. These findings suggested that c-Fos and c-Jun were induced selectively in reversibly damaged neurons, whereas HSP70 was up-regulated even in neurons with irreversible damage, but was more preferentially and intensely expressed in neurons with reversible damage.
热休克蛋白(HSP)和即早基因表达的神经保护作用仍不清楚。我们采用免疫电子显微镜技术,研究了沙土鼠短暂性脑缺血再灌注后,表达c-Fos、c-Jun和HSP70的神经元的超微结构完整性。在对缺血有抗性的CA3区观察到c-Fos和c-Jun的诱导表达,而HSP70不仅在CA3区表达,在易损的CA1区也有表达。通过免疫电子显微镜观察发现,除线粒体肿胀和多核糖体解聚外,在保持神经元完整性的神经元中可观察到c-Fos/c-Jun和HSP70的表达。相反,对HSP70无免疫反应的CA1神经元表现出细胞质空泡和粗面内质网平行堆积,这些特征与延迟性神经元死亡过程相关。这些发现表明,c-Fos和c-Jun在可逆性损伤的神经元中被选择性诱导,而HSP70即使在不可逆损伤的神经元中也会上调,但在可逆性损伤的神经元中表达更优先且更强烈。