Human Leptin Protein Induces Proliferation of A549 Cells via Inhibition of PKR-Like ER Kinase and Activating Transcription Factor-6 Mediated Apoptosis
Yonsei Medical Journal
;
: 1407-1415, 2013.
Artigo
em Inglês
| WPRIM
| ID: wpr-26575
ABSTRACT
PURPOSE:
To investigate the anti-apoptotic mechanism of leptin in non-small cell lung cancer. MATERIALS ANDMETHODS:
The influences of leptin on apoptosis were investigated, analyzing the mechanism that triggers growth of A549 cells. The effects of leptin on cell proliferation were examined by XTT analysis. Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), inositol requiring proteins-1, spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation initiation factor-2alpha, caspase-12 and CHOP protein were detected in four groups by western blot, and endoplasmic reticulum (ER) stress related mRNA were detected by reverse transcription PCR.RESULTS:
The expression of leptin in A549 and leptin transfected cells inhibited cisplatin activated ER stress-associated mRNA transcription and protein activation. Two ER stress unfolded protein response pathways, PERK and ATF6, were involved, and XBP1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) were increased significantly when treated with cisplatin in A549-siRNA against leptin cells. Furthermore, CHOP expression was inhibited upon leptin expression in A549, LPT-PeP and LPT-EX cells.CONCLUSION:
Leptin serves as an important factor that promotes the growth of A549 cells through blocking ER stress-mediated pathways. This blocking is triggered by p-Perk and ATF6 via inhibition of CHOP expression.
Texto completo:
DisponíveL
Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Western Blotting
/
Apoptose
/
EIF-2 Quinase
/
Reação em Cadeia da Polimerase Via Transcriptase Reversa
/
Leptina
/
Linhagem Celular Tumoral
/
Proliferação de Células
/
Fator 6 Ativador da Transcrição
Limite:
Humanos
Idioma:
Inglês
Revista:
Yonsei Medical Journal
Ano de publicação:
2013
Tipo de documento:
Artigo
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