[Back to Issue 12 ToC] [Back to Journal Contents] [Back to Biochemistry (Moscow) Home page]
[View Full Article] [Download Reprint (PDF)]

Human Leptin Triggers Proliferation of A549 Cells via Blocking Endoplasmic Reticulum Stress-Related Apoptosis

Wei Wang1#, Haicheng Yan2#, Changwu Dou2*, and Youle Su2

1Guangzhou Institute of Respiratory Diseases, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University, Guangzhou, 510120, China

2Neurosurgery, Affiliated Hospital of Inner Mongolia Medical University, Huhehaote, 010051, China; fax: +86 (0471) 663-7640; E-mail: changwudou@126.com

# These authors equally contributed to this work.

* To whom correspondence should be addressed.

Received May 4, 2013; Revision received September 13, 2013
Lung cancer is a disease characterized by uncontrolled cell growth in tissues of the lung. Leptin is a pleiotropic hormone with antiapoptotic and proliferative roles involved in several systems. However, there is no known antiapoptotic mechanism of leptin in non-small cell lung cancer (NSCLC). So, we investigated the antiapoptotic mechanism of leptin in NSCLC. Proliferation, apoptosis, and the specific mechanism of leptin-transfected cells were analyzed in this study. Leptin, p-Perk, IRE1, cleaved ATF6, spliced XBP1, eIF2-α, TRAF2, CHOP, and caspase 12 proteins were detected by Western blot, and endoplasmic reticulum (ER) stress-related mRNA was detected by semi-quantitative reverse transcription PCR (RT-PCR). Leptin in A549 and transfected cells inhibited cisplatin-activated ER stress-associated mRNA transcription and activation of proteins. ER stress unfolded protein response (UPR) proteins, PERK and ATF6, were involved in leptin-triggered apoptosis. XBP1 and TRAF2 were increased significantly when treated with cisplatin in A549-siLPT and non-transfected cells. CHOP expression was blocked in A549 and transfected cells (LPT-PeP and LPT-EX cells). In conclusion, leptin can promote the proliferation of A549 cells through blocking ER stress-mediated apoptosis. This blocking is mediated by the p-Perk and ATF6 pathway through blocking activation of CHOP.
KEY WORDS: apoptosis, ER stress, cell growth, leptin, TRAF2, XPB1

DOI: 10.1134/S0006297913120031