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

Abstract

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.