Thioredoxin Activates MKK4-NFκB Pathway in a Redox-dependent Manner to Control Manganese Superoxide Dismutase Gene Expression in Endothelial Cells

Abstract

Background:The mechanism underlying thioredoxin-induced expression of manganese superoxide dismutase (MnSOD) is unknown. Results: Reduced thioredoxin activates the MKK4-NFB pathway to repress MKK7-AP-1-mediated inhibition of MnSOD expression. Conclusion: Cellular redox status regulates gene expression via redox control of MKK4, an MAPK. Significance: This study reveals a novel mechanism underlying transcriptional regulation of MnSOD encoding a critical antioxidant enzyme.

Thioredoxin Uses a GSH-independent Route to Deglutathionylate Endothelial Nitric-oxide Synthase and Protect against Myocardial Infarction

“…5C). To further confirm the glutathionylation of eNOS, we implemented the proximity ligation assay (PLA) (28). As shown in Overexpression of Trx Restores eNOS Activity and NO Release-We analyzed the effect of Trx on eNOS enzymatic activity and NO release.…”

“…Transgenic mice with overexpression of hTrx (Trx-Tg) were bred and maintained in the animal facility of Texas Tech University Health Sciences Center and have been described previously (28,44). ␣MHC-Trx-Tg mice are a generous gift from Dr. Junichi Sadoshima, University of Medicine and Dentistry of New Jersey, and have been described previously (45).…”

“…C, Ad-LacZ-or Ad-Trx-infected H/R-treated HCAEC were analyzed for colocalization of eNOS and PrS-SG by immunofluorescence staining. D, Ad-LacZ-or Ad-Trx-infected HCAEC were exposed to H/R, and eNOS glutathionylation was examined by PLA as published previously (28). E, proximity signals (green foci) were counted and plotted as a bar graph.…”

Современные Возможности Идентификации Новых Молекул-Мишеней Для Фармакологической Коррекции Проницаемости Гематоэнцефалического Барьера

“…Ïðè èñïîëüçîâàíèè ñèíòåçèðîâàííî-ãî àâòîðàìè [75] ïåïòèäà-èíãèáèòîðà MKK7 çàôèêñè-ðîâàíî óìåíüøåíèå ðàçìåðîâ çîíû èíôàðêòà ãîëîâíî-ãî ìîçãà, ïðè÷åì ýôôåêò îêàçàëñÿ äëèòåëüíûì. Ñõîä-íûå ýôôåêòû îáíàðóaeåíû è ïðè óïðàâëåíèè àêòèâíî-ñòüþ MKK4 [41].…”

“…Òàêèì îáðàçîì, òèîðåäîêñèí àêòèâèðóåò ïîñëåäîâà-òåëüíî ÌÊÊ4, à òàêaeå JNK è NF-kB [41]. Èíòåðåñíî, ÷òî òèîðåäîêñèí îêàçûâàåò àêòèâèðóþùåå âëèÿíèå è íà HIF-1-ñèãíàëèíã, ýêñïðåññèþ ñîñóäèñòî-ýíäîòåëè-àëüíîãî ôàêòîðà ðîñòà è, òåì ñàìûì, ìîaeåò ó÷àñòâî-âàòü â àíãèîãåíåçå è ðåãóëÿöèè ïðîíèöàåìîñòè ÃÝÁ.…”