Spatio-temporal properties of 5-lipoxygenase expression and activation in the brain after focal cerebral ischemia in rats.
The role of 5-lipoxygenase (5-LOX) in brain injury after cerebral ischemia has been reported; however, the spatio-temporal properties of 5-LOX expression and the enzymatic activation are unclear. To determine these properties, we observed post-ischemic 5-LOX changes from 3 h to 14 days after reperfusion in rats with transient focal cerebral ischemia induced by 30 min of middle cerebral artery occlusion. We found that the expression of 5-LOX, both mRNA and protein, was increased in the ischemic core 12-24 h after reperfusion, and in the boundary zone adjacent to the ischemic core 7-14 days after reperfusion. The increased 5-LOX was primarily localized in the neurons in the ischemic core at 24 h, but in the proliferated astrocytes in the boundary zone 14 days after reperfusion. As 5-LOX metabolites, the level of cysteinyl-leukotrienes in the ischemic brain was substantially increased 3 h to 24 h, near control at 3 days, and moderately increased again 7 days after reperfusion; whereas the level of LTB(4) was increased mildly 3 h but substantially 7-14 days after reperfusion. Thus, we conclude that 5-LOX expression and the enzymatic activity are increased after focal cerebral ischemia, and spatio-temporally involved in neuron injury in the acute phase and astrocyte proliferation in the late phase.
Zhou
Yu
Y
Department of Pharmacology, School of Medicine, Zhejiang University, People's Republic of China.
Wei
Er-Qing
EQ
Fang
San-Hua
SH
Chu
Li-Sheng
LS
Wang
Meng-Ling
ML
Zhang
Wei-Ping
WP
Yu
Guo-Liang
GL
Ye
Yi-Lu
YL
Lin
Shu-Cai
SC
Chen
Zhong
Z
D000208:Acute Disease; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000096:biosynthesis* / Q000235:genetics; D001157:Arterial Occlusive Diseases / Q000378:metabolism; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D049109:Cell Proliferation; D002908:Chronic Disease; D004195:Disease Models, Animal; D004789:Enzyme Activation; D015870:Gene Expression; D007124:Immunoenzyme Techniques; D002546:Ischemic Attack, Transient / Q000201:enzymology* / Q000473:pathology; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors
D015289:Leukotrienes; D012333:RNA, Messenger; D001094:Arachidonate 5-Lipoxygenase