Delaney C L, Russell J W, Cheng H L, Feldman E L
Department of Neurology, University of Michigan, Ann Arbor, USA.
J Neuropathol Exp Neurol. 2001 Feb;60(2):147-60. doi: 10.1093/jnen/60.2.147.
Schwann cells (SCs), the myelinating cells of the peripheral nervous system, are lost or damaged in patients suffering from diabetic neuropathy. In the current study, 2 model systems are used to study the mechanism of SC damage in diabetic neuropathy: the streptozotocin (STZ)-treated diabetic rat and cultures of purified SCs in vitro. Electron microscopy of dorsal root ganglia from STZ-treated rats reveals classic ultrastructural features of apoptosis in SCs, including chromatin clumping and prominent vacuolation. Bisbenzamide staining of SCs cultured in hyperglycemic defined media shows nuclear blebbing of apoptotic cells. Insulin-like growth factor-I (IGF-I) is protective. LY294002, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor, blocks the effect of IGF-I. High glucose induces caspase cleavage in apoptotic SCs--an effect that is blocked by bok-asp-fmk (BAF), a caspase inhibitor. Although Bcl-xL expression remains unchanged in experimental conditions, over-expression of Bcl-xL protects SCs from apoptosis. In summary, hyperglycemia induces caspase activation and morphologic changes in SCs consistent with apoptotic death, both in vivo and in vitro. Over-expression of Bcl-xL, or IGF-I, signaling via PI 3-kinase, protects SCs from glucose-mediated apoptosis in vitro. IGF-I may be useful in preventing hyperglycemia-induced damage to SCs in patients suffering from diabetic neuropathy.
雪旺细胞（SCs）是周围神经系统的髓鞘形成细胞，在糖尿病性神经病变患者中会丢失或受损。在本研究中，使用了两种模型系统来研究糖尿病性神经病变中雪旺细胞损伤的机制：链脲佐菌素（STZ）处理的糖尿病大鼠和体外纯化雪旺细胞培养物。对STZ处理大鼠的背根神经节进行电子显微镜检查，发现雪旺细胞中有典型的凋亡超微结构特征，包括染色质凝聚和明显的空泡化。在高血糖限定培养基中培养的雪旺细胞经双苯甲酰胺染色显示凋亡细胞的核出泡。胰岛素样生长因子-I（IGF-I）具有保护作用。磷脂酰肌醇3-激酶（PI 3-激酶）抑制剂LY294002可阻断IGF-I的作用。高糖诱导凋亡雪旺细胞中的半胱天冬酶裂解——一种被半胱天冬酶抑制剂bok-asp-fmk（BAF）阻断的效应。尽管在实验条件下Bcl-xL表达保持不变，但Bcl-xL的过表达可保护雪旺细胞免于凋亡。总之，高血糖在体内和体外均可诱导雪旺细胞中的半胱天冬酶激活和与凋亡死亡一致的形态学变化。Bcl-xL的过表达或通过PI 3-激酶的IGF-I信号传导可在体外保护雪旺细胞免受葡萄糖介导的凋亡。IGF-I可能有助于预防糖尿病性神经病变患者中高血糖诱导的雪旺细胞损伤。
