Acidic stress induced G1 cell cycle arrest and intrinsic apoptotic pathway in Jurkat T-lymphocytes

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• 作者：Jee Young Kim ^{j.kim@uni-heidelberg.de} ; Xinlai Cheng ^{x.cheng@uni-heidelberg.de} ; Stefan Wö ; lfl ; ^{wolfl@uni-hd.de}
• 关键词：Jurkat T-lymphocyte ; Acidic stress ; Apoptosis ; Caspase-9 ; G1 phase ; Alkaline phosphatase (AP)
• 刊名：Experimental Cell Research
• 出版年：2017
• 出版时间：1 January 2017
• 年：2017
• 卷：350
• 期：1
• 页码：140-146
• 全文大小：752 K
• 卷排序：350

文摘

Low extracellular pH (pHe) is a common hallmark of tumor microenvironment, which will also affect pH sensitive T-lymphocytes in this environment. Due to the growing interest on T-cell mediated cancer therapies, acidic stress induced consequences on this lymphocyte deserves through investigations.ResultsIn line with our previous study [Kim et al., Biochem. Biophys. Res. Commun. 2016; 472(4): 585-91.], we applied sub-lethal acidic stress (pH 3.3, 37 °C for 25 min) to Jurkat T-lymphocytes. Progression from early apoptosis into late apoptosis was clearly observed by flow cytometry within 3 days. Treatment led to onset of G1 arrest in the first 24 h and cell cycling data corresponded to survival of an invasive alkaline phosphatase (AP) positive population. Concerning the massive cell death observed after 72 h, both mRNA level (qRT-PCR) and protein level (western blotting) data indicate programmed cell death through p53-p21 independent signaling.ConclusionTaken together, the results obtained suggest that the majority of Jurkat cells exposed to short but intense acidic stress conditions, as used here, undergo intrinsic apoptosis, while invasion and AP activation only occurred in a small surviving cell population.