Volume 4, Number 4, pp. 197-200
Manumycin restores the levels of cortical homocysteine, methionine and cysteine changed in ischaemia-evoked animals
L. Shanshiashvili1, E. Sekoyan2 and D. Mikeladze1
1
Institute of Physiology, Georgian Academy of Sciences, 14 Gotua St, 0160 Tbilisi, Georgia
2
Scientific Research Institute for Spa Treatment and Physical Medicine, Yerevan, Armenia
Reactive oxygen species (ROS) formed during ischaemia can activate the Ras signalling system, which amplifies the intracellular formation of ROS. Ras proteins induce senescence by altering the intracellular levels of ROS which leads to the impairment of homocysteine metabolism. The effects of the farnesyltransferase inhibitor, manumycin, were examined on ischaemia-evoked changed sulfur-containing amino acids. A rat four-vessel occlusion model was utilized to examine the effects of manumycin on cortical levels of homocysteine, methionine and cysteine. Cerebral ischaemia was induced by occlusion of the carotid arteries for 20 min in anaesthetized animals. Intraperitoneal injection of manumycin A (3 mg/kg body weight) was carried out 2 hours before anaesthesia. It was found that after ischaemia the quantities of methionine and homocysteine were decreased, whereas the amount of cysteine was increased. In the rats pretreated with manumycin, cerebral ischaemia does not change the content of methionine, homocysteine or cysteine. These results suggest that ischaemia-induced oxidative stress, acting through Ras-dependent processes, change homocysteine metabolism in the direction of trans-sulfuration.
Keywords: homocysteine, ischaemia, Ras