Distinct roles of CysLT1 and CysLT2 receptors in oxygen glucose deprivation-induced PC12 cell death.
Cysteinyl leukotrienes are involved in ischemic brain injury, and their receptors (CysLT(1) and CysLT(2)) have been cloned. To clarify which subtype mediates the ischemic neuronal injury, we performed permanent transfection to increase CysLT(1) and CysLT(2) receptor expressions in PC12 cells. Oxygen glucose deprivation (OGD)-induced cell death was detected by Hoechst 33258 and propidium iodide fluorescent staining as well as by flow cytometry. OGD induced late phase apoptosis mainly and necrosis minimally. Over-expression of CysLT(1) receptor decreased and over-expression of CysLT(2) receptor increased OGD-induced cell death. An agonist LTD(4) (10(-7)M) also induced apoptosis, especially in CysLT(2) receptor over-expressing cells. A selective CysLT(1) receptor antagonist montelukast did not affect OGD-induced apoptosis; while non-selective CysLT receptor antagonist Bay u9773 inhibited OGD-induced apoptosis, especially in CysLT(2) receptor over-expressing cells. Thus, CysLT(1) and CysLT(2) receptors play distinct roles in OGD-induced PC12 cell death; CysLT(1) attenuates while CysLT(2) facilitates the cell death.
Sheng
Wen-Wen
WW
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Li
Cheng-Tan
CT
Zhang
Wei-Ping
WP
Yuan
Yu-Mei
YM
Hu
Hua
H
Fang
San-Hua
SH
Zhang
Lei
L
Wei
Er-Qing
EQ
D000085:Acetates / Q000494:pharmacology; D000818:Animals; D006690:Bisbenzimidazole; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D003521:Cyclopropanes; D005434:Flow Cytometry; D005947:Glucose / Q000172:deficiency; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology*; D008565:Membrane Proteins / Q000502:physiology*; D051379:Mice; D016716:PC12 Cells; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D018077:Receptors, Leukotriene / Q000502:physiology*; D013189:SRS-A / Q000031:analogs & derivatives / Q000494:pharmacology; D013440:Sulfides
D000085:Acetates; C071435:BAY u9773; D003521:Cyclopropanes; D008565:Membrane Proteins; D011804:Quinolines; D018077:Receptors, Leukotriene; D013189:SRS-A; D013440:Sulfides; C412375:cysteinyl leukotriene receptor 2; D005947:Glucose; D006690:Bisbenzimidazole; C083169:leukotriene D4 receptor; C093875:montelukast