Distinct roles of CysLT sub(1) and CysLT sub(2) receptors in oxygen glucose deprivation-induced PC12 cell death

• Published in: Biochemical and biophysical research communications 2006-07, Vol.346 (1), p.19-25
• Main Authors: Sheng, W W, Li, C T, Zhang, W P, Yuan, Y M, Hu, H, Fang, SH, Zhang, L, Wei, E Q
• Format: Article
• Language: English
• ISSN: 0006-291X
• DOI: 10.1016/j.bbrc.2006.05.023

Cysteinyl leukotrienes are involved in ischemic brain injury, and their receptors (CysLT sub(1) and CysLT sub(2)) have been cloned. To clarify which subtype mediates the ischemic neuronal injury, we performed permanent transfection to increase CysLT sub(1) and CysLT sub(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 sub(1) receptor decreased and over-expression of CysLT sub(2) receptor increased OGD-induced cell death. An agonist LTD sub(4) (10 super(-) super(7)M) also induced apoptosis, especially in CysLT sub(2) receptor over-expressing cells. A selective CysLT sub(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 sub(2) receptor over-expressing cells. Thus, CysLT sub(1) and CysLT sub(2) receptors play distinct roles in OGD-induced PC12 cell death; CysLT sub(1) attenuates while CysLT sub(2) facilitates the cell death.