title: Acidic stress induced G1 cell cycle arrest and intrinsic apoptotic pathway in Jurkat T-lymphocytes.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  In 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 25min) 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 24h and cell cycling data corresponded to survival of an invasive alkaline phosphatase (AP) positive population. Concerning the massive cell death observed after 72h, both mRNA level (qRT-PCR) and protein level (western blotting) data indicate programmed cell death through p53-p21 independent signaling.
  
  
  CONCLUSIONS
  Taken 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.
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Pharmaceutical Biology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: j.kim@uni-heidelberg.de.
authors.forename: Jee Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Pharmaceutical Biology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: x.cheng@uni-heidelberg.de.
authors.forename: Xinlai
authors.initials: X
authors.lastname: Cheng
authors.affiliation: Institute of Pharmacy and Molecular Biotechnology, Pharmaceutical Biology, Heidelberg University, Im Neuenheimer Feld 364, D-69120 Heidelberg, Germany. Electronic address: wolfl@uni-hd.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wölfl
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D059447:Cell Cycle Checkpoints; D002455:Cell Division; D005434:Flow Cytometry / Q000379:methods; D059585:G1 Phase Cell Cycle Checkpoints / Q000502:physiology*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D019169:Jurkat Cells; D015398:Signal Transduction / Q000502:physiology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: Acidic stress; Alkaline phosphatase (AP); Apoptosis; Caspase-9; G1 phase; Jurkat T-lymphocyte