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Updated: Feb 4, 2026

Analysis of Oxidative Stress in Zebrafish Embryos
Published on: July 7, 2014
S1PR3 Inactivation Aggravates Cerebrovascular Endothelial Cell Permeability Mediated by cPLA2 and STAT3
1Department of Clinical Pharmacology, School of Pharmacy, Nanjing Medical University, Nanjing, China.
None:
Sphingosine-1-phosphate receptor-3 (S1PR3) has been implicated in the maintenance of cerebrovascular integrity during cerebral ischemia. This study aimed to elucidate the impact of S1PR3 inactivation on oxidative stress-induced cerebrovascular endothelial cell permeability and to explore the potential mechanisms. In bEnd3 cells, blockade of S1PR3 exacerbated H2O2-induced endothelial hyperpermeability, ZO-1 redistribution, reactive oxygen species (ROS) accumulation and cell viability loss. A previous study indicated that the activation of p38 and extracellular signal-regulated kinase (ERK) pathway was essential for H2O2-mediated cytosolic phospholipase A2 (cPLA2) phosphorylation in bEnd3 cells. This study revealed that the activation of c-Jun N-terminal kinase (JNK) was crucial for H2O2-induced signal transducer and activator of transcription 3 (STAT3) phosphorylation. In bEnd3 monolayer, either blockade or genetic knockdown of S1PR3 further enhanced the phosphorylation level of p38, ERK, cPLA2, JNK and STAT3 in response to H2O2 exposure. Furthermore, lentivirus-mediated knockdown of S1PR3 intensified H2O2-induced ZO-1 redistribution, paracellular hyperpermeability and ROS accumulation, while further compromising endothelial cell viability. Collectively, these results identified S1PR3 as a critical guardian of endothelial barrier integrity under oxidative stress, acting through cPLA2- and STAT3-dependent signalling pathways.
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