PLC-β1及丙酮酸媒介部分葡萄糖誘發之訊息傳導

吳致誼

doi:10.6342/NTU.2012.02731

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PLC-β1及丙酮酸媒介部分葡萄糖誘發之訊息傳導

PLC-β1 and pyruvate mediating part of the glucose-induced signaling pathway

吳致誼 , Masters　　Advisor：張震東　　

繁體中文 DOI： 10.6342/NTU.2012.02731

葡萄糖代謝；丙酮酸； PLC-β1 ； PKC ； ERK 1/2 ； glucose metablosim ； pyruvate ； PLC-β1 ； PKC ； ERK 1/2

Abstract │ Reference (95) │ Altmetrics

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Pyruvate is the end product of glycolysis. It may undergo the fermentation process leading to lactate or ethanol production, or enter the TCA cycle in the mitochondria to produce more energy. Like the other α-keto acids, pyruvate has the antioxidative property in which pyruvate reacts with hydrogen peroxide in a non-enzymatic way yielding acetate, carbon dioxide and water. Pyruvate has been considered as an important regulatory molecule in the carbohydrate metabolism affecting the velocity of glycolysis and TCA cycle by allosteric regulation. Recently many metabolites are considered to exert other physiological functions besides serving as metabolic intermediates. Using Affinity Elution from Tandem Hydrophobic Interaction Chromatography(AETHIC) and MS analysis, we discovered that PLC-β1 may be a pyruvate-binding protein. In addition, pyruvate induces PLC-β1 activation and translocation from cytosol to nucleus in glucose-starved HEK cells, leading to PKC activation. Similar result have been found in starved cells treated with glucose. These data confirmed that glucose-induced signal transduction may be mediated by pyruvate and PLC-β1. Treatment of pyruvate also activates the ERK-MAPK pathway. However we have found that activation of PLC-β1 and ERK are two independent pathways. In the presence of exogenous pyruvate, both normal cells and cells over-expressing PLC-β1 survive better than cells without pyruvate. Therefore, pyruvate serves as a signal molecules in cells with a high flux of glycolysis.

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