• Ghrelin Induces Autophagy Via deacetylation of LC3 by SIRT1 in Jurkat and Molt-4 Cells
  • Masoud Heshmati,1,* Mohammad-Javad Sanaei,2 Mehrnaz Ravari,3
    1. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
    2. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran
    3. Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran


  • Introduction: Leukemia is one of the most frequent malignancies in children. Although the treatment improved in the last decades, it is failed in 30% of cases. Ghrelin is a small peptide hormone that in addition to feeling hungry and stimulating the release of growth hormone, it increases autophagy in cancer cells. SIRT1 is an NAD+ - associated deacetylase that plays a key role in the control of cellular vital activities such as autophagy, metastasis, and induction of apoptosis. given the importance of elucidating the role of ghrelin and SIRT1 in induction of proteins involved in autophagy, we decided to investigate the effect of these factors on GHSR expression and autophagy on Jurkat and Molt4 cell lines
  • Methods: Jurkat and Molt4 cells were cultured in RPMI 1640 medium and treated with 10nM ghrelin, 50μM Ex-527. Cell proliferation was assessed by MTS assay, induced apoptosis and expression of GHS-R1a by flow cytometry and induction of autophagy by western blot After 6 and 24 hours of adding hormones and inhibitors.
  • Results: The results showed that SIRT1 expression was upregulated the time-dependent during induction of autophagy by ghrelin in Jurkat and Molt4 cells and was also inhibited by inactivation of SIRT1. Our data showed that ghrelin can induce autophagy via deacetylation of LC3 and decrease GHS-R1a expression the time-dependent, as well as increased regulation of SIRT1 in Jurkat and Molt4 cells, and that SIRT1 is an essential protein for ghrelin induction of autophagy.
  • Conclusion: The results of the present study showed that ghrelin induces autophagy and down-regulation of the ghrelin receptor (GHS-R1a) expression by SIRT1 in Jurkat and Molt4 cells. Ghrelin-induced autophagy did not lead to cell death due to the weak apoptosis and proliferation and invasion observed at 6 and 24 h of autophagy.
  • Keywords: Ghrelin, SIRT1, T-ALL, GHS-R1a, Autophagy