Schisandrin B ameliorates high-glucose-induced vascular endothelial cells injury by regulating the Noxa/Hsp27/NF-[kappa]B signaling pathway

Background: To address the molecular mechanism of the anti-inflammation effects of schisandrin B (Sch B) in atherosclerosis, we examined injured HMEC-1, HBMEC, and HUVEC-12 cells induced by high glucose (HG). Methods: Western blot was performed to detect the levels of the proteins Hsp27, Noxa, TLR5, p-I[kappa]B[alpha], and p-p65 in HG-induced cells, while ELISA was used to analyze the inflammatory cytokines TNF-[alpha], IL-6, MCP-1, and IL-1[beta] in cells with Hsp27 or Noxa stable expression. Results: Overexpression of Hsp27 upregulated the inflammatory cytokines and the release of I[kappa]B[alpha], promoted transportation of p65 into the nucleus, and lastly, affected the inflammation process, while Sch B counteracted the upregulation. In addition, the effect of Noxa overexpression, which is different from Hsp27 overexpression, was consistent with that of Sch B treatment. Conclusions: Sch B may inhibit the inflammatory cascade and alleviate the injury to HMEC-1, HBMEC, and HUEVC-12 cells caused by HG by regulating the Noxa/Hsp27/NF-[kappa]B signaling pathway. Key words: atherosclerosis, high glucose, Hsp27, inflammation, NF-[kappa]B, Noxa, schisandrin B. Contexte : Afin de comprendre le mecanisme moleculaire des effets anti-inflammatoires de la Sch B dans l'atherosclerose, les auteurs ont examine les cellules HMEC-1, HBMEC et HUVEC-12 endommagees par une concentration elevee de glucose. Methodes : Le transfert Western a ete realise pour detecter les niveaux proteiques de Hsp27, Noxa, TLR5, p-I[kappa]B[alpha] et p-p65 chez les cellules placees en presence de concentrations elevees de glucose, alors que le dosage ELISA a ete utilise pour analyser la presence des cytokines inflammatoires TNF-[alpha], IL-6, MCP-1 et IL-1[beta] dans les cellules exprimant Hsp27 et Noxa de facon stable. Resultats: La surexpression de Hsp27 regulait a la hausse les cytokines inflammatoires et la liberation d'I[kappa]B[alpha], favorisait le transport de p65 dans le noyau et affectait finalement le processus inflammatoire, alors que la Sch B contrecarrait cette regulation a la hausse. De plus, la surexpression de Noxa dont l'effet est different de celui de la surexpression de Hsp27, correspondait a l'effet du traitement a la Sch B. Conclusions : La Sch B peut inhiber la cascade inflammatoire et attenuer le dommage provoque par une concentration elevee de glucose dans les cellules HMEC-1, HBMEC et HUVEC-12 en regulant la voie de signalisation Noxa/Hsp27/NF-[kappa]B. [Traduit par la Redaction] Mots-cles: atherosclerose, concentration elevee de glucose, Hsp27, inflammation, NF-[kappa]B, Noxa, schisandrine B.
Introduction Atherosclerosis (AS) is a common disease that seriously harms human health and is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases, such as coronary heart disease, cerebrovascular [...]