title: Tetrahydropalmatine protects rat pulmonary endothelial cells from irradiation-induced apoptosis by inhibiting oxidative stress and the calcium sensing receptor/phospholipase C-γ1 pathway.
abstract: The aim of this study was to confirm the protective effect of tetrahydropalmatine (THP) against irradiation-induced rat pulmonary endothelial cell apoptosis and to explore the underlying mechanism, with a focus on the calcium-sensing receptor (CaSR)/phospholipase C-γ1 (PLC-γ1) pathway. We established a model of irradiation-induced primary rat pulmonary endothelial cell injury. Cell apoptosis and mitochondrial membrane potential (Δψm) were measured by flow cytometry. The expression of CaSR, cytochrome c, PLC-γ1, reactive oxygen species (ROS) and [Ca(2+)]i was also determined. Caspase-3 and caspase-9 activities were measured using commercial kits. Inositol triphosphate (IP3) and the production of inflammatory cytokines were detected by enzyme-linked immunosorbent assay. The results showed that THP significantly inhibited irradiation-induced cell apoptosis and intracellular accumulation of ROS. Pretreatment with THP significantly decreased the expression of CaSR, inhibited the CaSR/PLC-γ1 pathway and subsequent [Ca(2+)]i overload stimulated by irradiation. THP, NPS2390 (inhibitor of CaSR), U73122 (inhibitor of PLC-γ1) and 2-APB (inhibitor of IP3) further decreased cell apoptosis, along with down-regulation of cytochrome c, caspase-3 and caspase-9 activation, disruption of Δψm and the production of inflammatory cytokines. These findings suggest that THP protects primary rat pulmonary endothelial cells against irradiation-induced apoptosis by inhibiting oxidative stress and the CaSR/PLC-γ1 pathway.
authors.affiliation: a Department of Oncology, Beijing Friendship Hospital , Capital Medical University , Xicheng District , Beijing , P.R. China ;
authors.forename: J
authors.initials: J
authors.lastname: Yu
authors.affiliation: a Department of Oncology, Beijing Friendship Hospital , Capital Medical University , Xicheng District , Beijing , P.R. China ;
authors.forename: L
authors.initials: L
authors.lastname: Zhao
authors.affiliation: a Department of Oncology, Beijing Friendship Hospital , Capital Medical University , Xicheng District , Beijing , P.R. China ;
authors.forename: L
authors.initials: L
authors.lastname: Liu
authors.affiliation: a Department of Oncology, Beijing Friendship Hospital , Capital Medical University , Xicheng District , Beijing , P.R. China ;
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.affiliation: b Department of Oncology , Guang An Men Hospital of Chinese Medica Science Research Institute , Xicheng District , Beijing , P.R. China.
authors.forename: X
authors.initials: X
authors.lastname: Zhu
authors.affiliation: a Department of Oncology, Beijing Friendship Hospital , Capital Medical University , Xicheng District , Beijing , P.R. China ;
authors.forename: B
authors.initials: B
authors.lastname: Cao
mesh_terms: D000818:Animals; D017209:Apoptosis; D001600:Berberine Alkaloids / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D018384:Oxidative Stress; D051966:Phospholipase C gamma / Q000378:metabolism*; D051381:Rats; D044169:Receptors, Calcium-Sensing / Q000378:metabolism*
chemical_list: D001600:Berberine Alkaloids; D044169:Receptors, Calcium-Sensing; C014215:tetrahydropalmatine; D051966:Phospholipase C gamma
keywords: Calcium-sensing receptors; endothelial cells; irradiation; oxidative stress; tetrahydropalmatine