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Molecular and Cellular Biochemistry

, Volume 444, Issue 1–2, pp 17–25 | Cite as

Tomatidine inhibits tumor necrosis factor-α-induced apoptosis in C2C12 myoblasts via ameliorating endoplasmic reticulum stress

  • Seung-Eun Song
  • Su-Kyung Shin
  • Hyun-Woo Cho
  • Seung-Soon Im
  • Jae-Hoon Bae
  • Seon Min Woo
  • Taeg-Kyu Kwon
  • Dae-Kyu Song
Article

Abstract

In this study, we examined the effect of tomatidine on tumor necrosis factor (TNF)-α-induced apoptosis in C2C12 myoblasts. TNF-α treatment increased cleaved caspase 3 and cleaved poly (ADP-ribose) polymerase (PARP) protein levels in a dose- and time-dependent manner. Pretreatment of cells with 10 μM tomatidine prevented TNF-α-induced apoptosis, caspase 3 cleavage, and PARP cleavage. Cells were treated with 100 ng/mL TNF-α for 24 h, and flow cytometry was utilized to assess apoptosis using annexin-V and 7-aminoactinomycin D. TNF-α up-regulated activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) expression. This effect was suppressed by pretreatment with tomatidine. Pretreatment with 4-phenylbutyric acid (a chemical chaperone) also inhibited TNF-α-induced cleavage of caspase 3 and PARP and up-regulation of ATF4 and CHOP expression. In addition, tomatidine-mediated inhibition of phosphorylation of c-Jun amino terminal kinase (JNK) attenuated TNF-α-induced cleavage of PARP and caspase 3. However, tomatidine did not affect NF-κB activation in TNF-α-treated C2C12 myoblast cells. Taken together, the present study demonstrates that tomatidine attenuates TNF-α-induced apoptosis through down-regulation of CHOP expression and inhibition of JNK activation.

Keywords

Tomatidine TNF-α C2C12 myoblast ER stress Apoptosis 

Notes

Acknowledgements

This study was funded by National Research Foundation of Korea (NRF) grants funded by the Korean Government (MSIP; Nos. 2014R1A5A2010008, 2013R1A2A2A01068220), and partially by iPET (Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries), Ministry for Food, Agriculture, Forestry and Fisheries, Republic of Korea [Grant Number 110135-3]. The authors appreciate Dr. Choi BK for theoretical supports.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2017

Authors and Affiliations

  1. 1.Department of Physiology & Obesity-Mediated Disease Research CenterKeimyung University School of MedicineDaeguSouth Korea
  2. 2.Department of Immunology & Obesity-Mediated Disease Research CenterKeimyung University School of MedicineDaeguSouth Korea

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