Gorio A, Donadoni M L, Finco C, Borella F, Di Giulio A M
Department of Medical Pharmacology, University of Milano, Italy.
Eur J Pharmacol. 1996 Sep 5;311(1):21-8. doi: 10.1016/0014-2999(96)00351-2.
This study monitored the extranuclear endogenous mono ADP-ribosylation of proteins. At least 10 proteins were ADP-ribosylated in a crude extract from control superior cervical ganglia, and 7 were labeled in control dorsal root ganglia; whereas in the diabetic rat the extent of labeling was reduced. These data suggest that proteins of peripheral ganglia are excessively ADP-ribosylated in vivo. Treatment of diabetic animals with silybin, a flavonoid with ADP-ribosyltransferase inhibitory activity, did not affect hyperglycemia, but prevented the alterations in the extent of mono-ADP-ribosylation of proteins. This effect was associated with the prevention of substance P-like immunoreactivity loss in the sciatic nerve. In the membrane fraction of sciatic nerve Schwann cells, at least 9 proteins were ADP-ribosylated, in diabetic rats the extent of labeling was increased. A comparable increase involving the same proteins was triggered by chronic nerve injury and by corticosteroid treatment. Silybin treatment of diabetic rats prevented such an increase. We propose that the inhibition of excessive protein mono-ADP-ribosylation by silybin prevented the onset of diabetic neuropathy, while the silybin effect on mono-ADP-ribosylation of Schwann cells is likely indirect and secondary to the improvement of diabetic axonopathy.
本研究监测了蛋白质的核外内源性单 ADP 核糖基化。在来自对照颈上神经节的粗提物中，至少有 10 种蛋白质发生了 ADP 核糖基化，在对照背根神经节中有 7 种被标记；而在糖尿病大鼠中，标记程度降低。这些数据表明，外周神经节的蛋白质在体内过度进行 ADP 核糖基化。用具有 ADP 核糖基转移酶抑制活性的类黄酮水飞蓟宾治疗糖尿病动物，并不影响高血糖，但可防止蛋白质单 ADP 核糖基化程度的改变。这种作用与坐骨神经中 P 物质样免疫反应性丧失的预防有关。在坐骨神经施万细胞的膜组分中，至少有 9 种蛋白质发生了 ADP 核糖基化，在糖尿病大鼠中标记程度增加。慢性神经损伤和皮质类固醇治疗引发了涉及相同蛋白质的类似增加。水飞蓟宾治疗糖尿病大鼠可防止这种增加。我们提出，水飞蓟宾对过度蛋白质单 ADP 核糖基化的抑制作用可预防糖尿病性神经病变的发生，而水飞蓟宾对施万细胞单 ADP 核糖基化的作用可能是间接的，且继发于糖尿病性轴突病的改善。
