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

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.

Inhibition of p21 and Akt Potentiates SU6656-Induced Caspase-Independent Cell Death in FRO Anaplastic Thyroid Carcinoma Cells

“…PI3K/Akt signaling plays crucial roles in insulin/IGF-1-mediated cell cycle progression and cell growth in FRTL5 thyroid cells [ 20 ] . We reported that alpha-lipoic acid ameliorates endoplasmic reticulum stress-induced cell death in FRTL5 thyroid cells by activating PI3K/Akt signaling [ 35 ] . PI3K/Akt signaling, which promotes cell survival, is deregulated in cancer cells including ATC cells [ 19 , 21 ] .…”

CCAAT/Enhancer-binding Protein-Homologous Protein Sensitizes to SU5416 by Modulating p21 and PI3K/Akt Signal Pathway in FRO Anaplastic Thyroid Carcinoma Cells

“…CHOP has pivotal roles in regulation of growth and survival through various signal pathways during ER stress [ 22 , 23 ] . Recently, we have reported that alpha-lipoic acid represses cell death in conjunction with CHOP downregulation in FRTL5 thyroid cells exposed to ER stress [ 24 ] . However, whether CHOP aff ects cell survival in ATC cells subjected to SU5416 has not been elucidated.…”

“…CHOP stimulated by TRB3 leads to cell death through inhibition of PI3K/Akt signal pathway during unfolded protein response in rat pancreatic islets [ 32 ] . Alphalipoic acid ameliorates ER stress-induced cell death by activating PI3K/Akt signal pathway in FRTL5 thyroid cells [ 24 ] . In our study, p21 and phospho-Akt protein levels were diminished in CHOP plasmid transfection before SU5415 treatment.…”

Selenium supplementation modulates apoptotic processes in thyroid follicular cells

“…Several pharmacological agents, such as TN, can also induce these effects. TN determines the cell death by disrupting endoplasmic reticulum (ER) integrity . The present study demonstrates that Se supplementation prevents TN‐induced apoptosis and cell death in FRTL5 cells.…”