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MG132
About: MG132 is a research topic. Over the lifetime, 1499 publications have been published within this topic receiving 56589 citations. The topic is also known as: MG132 & Z-Leu-leu-leu-al.
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TL;DR: EnaC stimulation following proteasomal inhibition is due to an accumulation of active SGK1 resulting in increased expression of ENaC at the cell surface, suggesting that inhibition of the proteasome mimicsSGK1-dependent stimulation of EN aC by aldosterone.
Abstract: The epithelial sodium channel (ENaC) marks the tightly regulated, rate-limiting step of sodium re-absorption in the aldosterone-sensitive distal nephron (ASDN). Stimulation of ENaC activity by aldosterone involves the serum and glucocorticoid-induced kinase 1 (SGK1) and is mediated via complex mechanisms including inhibition of channel retrieval. Retrieved channels may be recycled or degraded, e.g. by the proteasomal pathway. The aim of the present study was to investigate whether inhibitors of the proteasome affect ENaC activity and surface expression, and to explore a possible involvement of SGK1. Short circuit current (I SC) measurements were performed on confluent mCCDcl1 murine cortical collecting duct cells to investigate the effect of two distinct proteasomal inhibitors, MG132 and bortezomib, on amiloride-sensitive ENaC-mediated I SC. Both inhibitors robustly stimulated amiloride-sensitive I SC. The time course and magnitude of the stimulatory effect of the proteasomal inhibitors on I SC were similar to those of aldosterone. Both, MG132 and aldosterone, significantly increased the abundance of β-ENaC at the cell surface. SGK1 activity was assessed by monitoring the phosphorylation of a downstream target, NDRG1, and was found to be increased by MG132. Importantly, inhibiting SGK1 activity prevented not only the stimulatory effect of aldosterone but also that of proteasomal inhibition. In conclusion, these data suggest that ENaC stimulation following proteasomal inhibition is due to an accumulation of active SGK1 resulting in increased expression of ENaC at the cell surface. Thus, inhibition of the proteasome mimics SGK1-dependent stimulation of ENaC by aldosterone.
14 citations
TL;DR: It is proposed that 14-3-3 proteins promote the dimerization of SCF(AtFBS1), which also may enhance the AtFBS 1 autoubiquitination activity and its degradation by the 26S proteasome.
14 citations
TL;DR: The inhibition of melanogenesis in B16F10 mouse melanoma cells by TQ treatment resulted from the inhibition of the β‑catenin pathway and confirmed that TQtreatment inhibition in zebrafish was confirmed.
Abstract: Thymoquinone (TQ) is a component found in the seeds of Nigella sativa, an annual plant growing on the Mediterranean coast, and is known for its anticancer and anti‑inflammatory effects. However, to date, at least to the best of our knowledge, limited studies are available examining the molecular mechanisms through which TQ inhibits melanogenesis. Accordingly, this study aimed to treat B16F10 mouse melanoma cells with TQ to investigate its apparent effects and its molecular regulatory mechanisms. Treatment of the B16F10 cells with 10, 15 and 20 µM of TQ for 48 h resulted in a dose‑dependent decrease in the expression of microphthalmia‑associated transcription factor (MITF), tyrosinase expression and tyrosinase activity, and these treatments simultaneously led to a decrease in the protein expression and transcription of β‑catenin, a Wnt signaling pathway protein. Pre‑treatment of the cells with the proteasome inhibitor, MG132, to confirm the inhibition of melanogenesis through the β‑catenin pathway by TQ treatment resulted in an increase in the expression of β‑catenin that was initially reduced by TQ, and the expression and activity of MITF and tyrosinase also increased. Pre‑treatment with LiCl, which is known to inactivate glycogen synthase kinase 3β (GSK3β) by inducing the phosphorylation of the Ser‑9 site, resulted in an increased phospho‑GSK3β expression accompanied by β‑catenin that was initially reduced by TQ, and the recovery of the expression and activity of tyrosinase was also confirmed. The transfection of S37A cDNA into B16F10 cells that overexpress β‑catenin resulted in the recovery of β‑catenin expression that was initially reduced by TQ, and this treatment also recovered the expression and activity of tyrosinase. When zebrafish eggs were treated with 1, 2.5 and 5 µM of TQ at 10 h following fertilization, their melanin content decreased in a dose‑dependent manner. On the whole, these findings demonstrated that the inhibition of melanogenesis in B16F10 mouse melanoma cells by TQ treatment resulted from the inhibition of the β‑catenin pathway and confirmed that TQ treatment inhibited melanogenesis in zebrafish.
14 citations
TL;DR: There is a limit to how far T. reesei Rut-C30, already under secretion stress, can be pressed to produce higher protein yields, according to the effect of proteasome inhibition on protein quality control in filamentous fungi.
14 citations
TL;DR: The results showed that the CE method was powerful, sensitive, and fast and required little sample and could be employed as one of the reliable drug screening methods for 20S proteasome inhibitors.
14 citations