Tian Tian

Publications (3)10.13 Total impact

• Article: Oscillation of mitogen-activated protein kinases in response to endoplasmic reticulum stress.

  Hui Zhang, Yang Zhao, Tian Tian, Adrienne W Paton, James C Paton, Masanori Kitamura
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  ABSTRACT: Periodic patterns of biochemical systems determine the function, behavior, and fate of eukaryotic cells. The cascades of mitogen-activated protein (MAP) kinases play crucial roles in a diverse range of cell function, and recent reports indicate that oscillation of extracellular signal-regulated kinase (ERK) activity is observed following stimulation by some growth factors. In the current report, we provide evidence that ERK and c-Jun N-terminal kinase, but not p38 MAP kinase, are activated periodically in response to endoplasmic reticulum stress. When activity of MAP kinases is evaluated, their oscillatory property should be considered carefully, especially under stress conditions.
  Analytical Biochemistry 10/2011; 417(2):292-4. · 3.00 Impact Factor
• Article: Cytoprotective roles of ERK and Akt in endoplasmic reticulum stress triggered by subtilase cytotoxin.

  Tian Tian, Yang Zhao, Shotaro Nakajima, Tao Huang, Jian Yao, Adrienne W Paton, James C Paton, Masanori Kitamura
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  ABSTRACT: Subtilase cytotoxin (SubAB) is the prototype of a distinct AB(5) toxin family produced by Shiga toxigenic Escherichia coli. Recent reports disclosed pro-apoptotic pathways triggered by SubAB, whereas its anti-apoptotic signals have not been elucidated. In the present study, we investigated pro-survival signaling elicited by SubAB, especially focusing on extracellular signal-regulated kinase (ERK) and Akt. We found that SubAB activated ERK and Akt, and inhibition of individual kinases enhanced SubAB-triggered apoptosis. SubAB induced endoplasmic reticulum (ER) stress, and other ER stress inducers mimicked the stimulatory effects of SubAB on ERK and Akt. Attenuation of ER stress reduced SubAB-induced phosphorylation of these kinases, suggesting involvement of the unfolded protein response (UPR). SubAB induced activation of protein kinase-like ER kinase (PERK) and phosphorylation of eukaryotic translation initiation factor 2α (eIF2α), and phosphorylation of eIF2α by salubrinal caused activation of ERK and Akt, leading to cell survival. Dominant-negative inhibition of PERK enhanced SubAB-induced apoptosis and reduced phosphorylation of ERK and Akt. Furthermore, the anti-apoptotic effect of eIF2α was significantly reversed by inhibition of ERK and Akt. These results suggest cytoprotective roles of ERK and Akt in SubAB-triggered, ER stress-mediated apoptosis.
  Biochemical and Biophysical Research Communications 06/2011; 410(4):852-8. · 2.48 Impact Factor
• Article: Subtilase cytotoxin activates MAP kinases through PERK and IRE1 branches of the unfolded protein response.

  Yang Zhao, Tian Tian, Tao Huang, Shotaro Nakajima, Yukinori Saito, Shuhei Takahashi, Jian Yao, Adrienne W Paton, James C Paton, Masanori Kitamura
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  ABSTRACT: Recent reports suggested involvement of mitogen-activated protein (MAP) kinases in the pathogenesis of Shiga toxin-induced hemolytic uremic syndrome (HUS). In the present study, we investigated a role for subtilase cytotoxin (SubAB), a possible trigger for HUS, in the regulation of MAP kinases. Treatment of cells with SubAB caused phosphorylation of c-Jun NH(2)-terminal kinase, extracellular signal-regulated kinase (ERK), and p38 MAP kinase. It was associated with activation of activator protein 1 (AP-1) and induction of AP-1-dependent transcription. SubAB induced the unfolded protein response (UPR) and consequently caused MAP kinase activation. SubAB led to induction of three major branches of the UPR, and the protein kinase-like endoplasmic reticulum kinase and inositol-requiring ER-to-nucleus signal kinase 1 pathways were responsible for the activation of MAP kinases. These results elucidated the potential of SubAB to trigger MAP kinase pathways via the UPR, which may contribute to the pathogenesis of Shiga toxin-induced HUS.
  Toxicological Sciences 12/2010; 120(1):79-86. · 4.65 Impact Factor