Positive feedback role of TRPC3 in TNF-α-mediated vasogenic edema formation induced by status epilepticus independent of ETB receptor activation. (19th November 2016)

• Record Type: Journal Article
• Authors: Min, Su-Ji; Kang, Tae-Cheon
• Is Part Of: Neuroscience. Volume 337(2016)
• Page Start: 37
• Page End: 47
• Publication Date: 2016-11-19
• Subjects: ANOVA analyzed by one-way analysis of variance -- BBB brain–blood barrier -- DAB 3, 3-diaminobenzidine -- DTT dithiothreitol -- eNOS endothelial nitric oxide synthase -- ET-1 endothelin-1 -- NFκB nuclear factor-κB -- NO nitric oxide -- PC piriform cortex -- RCA Ricinus Communis Agglutinin I -- SE status epilepticus -- TBS Tris-buffered saline -- TNF tumor necrosis factor -- TRPC transient receptor potential canonical channel; ET-1 -- NFκB -- Pyr-3 -- TNF-α -- TRPC3 -- status epilepticus; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2016.09.005
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: TRPC3 was up-regulated during vasogenic edema formation induced by SE. sTNFp55R and SN50 (but not BQ-788) inhibited up-regulated TRPC3 expression following SE. Pyr-3 ameliorated SE-induced NFκB p65-Thr485 phosphorylation and ETB receptor expression. Pyr-3 also mitigated NFκB p65-Thr485 phosphorylation induced by recombinant TNF-α. TRPC3 may be involved in a positive feedback loop of ETB receptor and NFκB signaling pathway. Abstract: Brain–blood barrier (BBB) disruption results in vasogenic edema, which is involved in the pathogenesis of epilepsy. Following status epilepticus (SE), up-regulated transient receptor potential canonical channel-3 (TRPC3), a Ca 2+ -permeable cation channels in endothelial cells, is relevant to vasogenic edema formation in the rat piriform cortex. In addition, pyrazole-3 (Pyr-3, a TRPC3 inhibitor) attenuated SE-induced vasogenic edema. However, the upstream regulators of TRPC3 expression in vasogenic edema formation have been unclear. In the present study, soluble tumor necrosis factor p55 receptor (sTNFp55R, a TNF-α inhibitor), SN50 (a nuclear factor-κB (NFκB) inhibitor), BQ-788 (an endothelin B (ETB ) receptor inhibitor) and Pyr-3 effectively prevented vasogenic edema following SE. sTNFp55R and SN50 (but not BQ-788) attenuated SE-induced up-regulation of endothelial TRPC3 expression. Pyr-3 ameliorated SE-induced NFκB p65-Thr435 phosphorylation and ETB receptor expression. In addition, Pyr-3 mitigated NFκB p65-Thr435 phosphorylation induced by recombinant TNF-α. These findings indicate that TNF-α-mediated NFκB p65-Thr435 phosphorylation may up-regulate TRPC3 expression, which participates in vasogenic edema formation via increasing endothelial nitric oxide synthase expression following SE, independent of ETB receptor activation. Therefore, we suggest that TRPC3 may be involved in a positive feedback loop of NFκB/ETB receptor signaling pathway.