Horm Metab Res 2011; 43(7): 445-451
DOI: 10.1055/s-0031-1277182
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

Alpha-Lipoic Acid Inhibits Endoplasmic Reticulum Stress-induced Cell Death Through PI3K/Akt Signaling Pathway in FRTL5 Thyroid Cells

S. J. Lee1 , S. H. Kim1 , J. G. Kang1 , C. S. Kim1 , S.-H. Ihm1 , M. G. Choi1 , H. J. Yoo1
  • 1Division of Endocrinology and Metabolism, Department of Internal Medicine, College of Medicine, Hallym University, Chuncheon, Republic of Korea
Further Information

Publication History

received 11.01.2011

accepted 12.04.2011

Publication Date:
17 May 2011 (online)

Abstract

Alpha-lipoic acid (ALA) has been shown to modulate cell death via PI3K/Akt signal pathway in various cells. In the present study, the effects of ALA on cell death and PI3K/Akt signal pathway linked to cell death-related proteins during endoplasmic reticulum (ER) stress in FRTL5 thyroid cells were evaluated. In FRTL5 thyroid cells, cell viability increased by ALA pretreatment in tunicamycin (TN)-treated cells. When TN was treated, CCAAT/enhancer-binding protein-homologous protein (CHOP) and Bax protein levels were elevated while Bcl-2 protein levels were reduced. ALA diminished CHOP and Bax protein levels, and augmented Bcl-2 protein levels in TN-treated cells. After exposure to TN, phospho-Akt protein levels were repressed whereas total Akt protein levels were not changed. ALA increased phospho-Akt protein levels but not total Akt protein levels in both non-TN-treated and TN-treated cells. After LY294002 administration in non-TN-treated cells, cell viability was reduced, and CHOP and Bax protein levels were elevated, and Bcl-2 protein levels were reduced. The CHOP, Bcl-2 and Bax protein levels were not different after LY294002 administration in TN-treated cells. LY294002 and wortmannin decreased cell viability, and increased CHOP and Bax protein levels, and decreased Bcl-2 protein levels in ALA-pretreated and TN-treated cells. In conclusion, these results suggest that ER stress may induce cell death by modulating PI3K/Akt signal pathway linked to cell death-related proteins in FRTL5 thyroid cells. Moreover, these findings imply that ALA may ameliorate ER stress-induced cell death by activating PI3K/Akt signal pathway and attenuating changes of cell death-related proteins in FRTL5 thyroid cells.

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Correspondence

Prof. S. J. LeeMD, PhD 

Division of Endocrinology and

Metabolism

Department of Internal

Medicine

College of Medicine

Hallym University

200-704 Chuncheon

Republic of Korea

Phone: +82/31/380 3700

Fax: +82/31/383 3768

Email: leesj@hallym.ac.kr