manumycin and Subarachnoid-Hemorrhage

Cerebral vasospasm is the major factor of mortality and morbidity in the patients who have an aneurysmal subarachnoid hemorrhage (SAH). Erythrocyte lysate (hemolysate), oxyhemoglobin (OxyHb), and bloody cerebrospinal fluid (CSF) are the causative agents for vasospasm. However, the signal transduction pathways for the action of these spasmogens are not clear. In this study, we examined the possible effect of these spasmogens on the p21Ras protein, an important factor in the signal cascade, in rabbit basilar artery. Hemolysate enhanced p21Ras precipitation over a 7-day period. The initial increase of p21Ras precipitation occurred after the tissues were incubated for 2 days with hemolysate. The peak effect of hemolysate, which was markedly increased compared with control (P<0.05, ANOVA), was observed on day 3. OxyHb and blood CSF, in contrast, failed to produce consistent or marked changes in p21Ras precipitation. p21Ras inhibitors FTPase inhibitor 1 and manumycin abolished hemolysate-induced enhancement of p21Ras immunoprecipitation. Genistein, a tyrosine kinase inhibitor, failed to reduce the effect of hemolysate on p21Ras. We concluded that hemolysate activates p21Ras in the rabbit basilar artery.

Topics: Animals; Basilar Artery; Dogs; Enzyme Activation; Enzyme Inhibitors; Erythrocytes; Female; Genistein; Hemolysis; Humans; In Vitro Techniques; Male; Oxyhemoglobins; Polyenes; Polyunsaturated Alkamides; Precipitin Tests; Protein-Tyrosine Kinases; Proto-Oncogene Proteins p21(ras); Rabbits; Subarachnoid Hemorrhage; Vasospasm, Intracranial