Humanin Peptides Regulate Calcium Flux in the Mammalian Neuronal, Glial and Endothelial Cells under Stress ConditionsAnna Knapp*, Urszula Czech, Anna Polus, Monika Chojnacka, Agnieszka Sliwa, Magdalena Awsiuk, Barbara Zapala, Dominika Malinska, Adam Szewczyk and Aldona Dembinska-Kiec
Department of Clinical Biochemistry, Jagiellonian University Medical College, Kraków, Poland
Laboratory of Intracellular Ion Channels, Nencki Institute of Experimental Biology, Warsaw, Poland
- *Corresponding Author:
- Anna Knapp, M.D, Ph.D
Department of Clinical Biochemistry
Jagiellonian University Medical College
ul. Kopernika 15A, 30-301 Kraków, Poland
Tel: +48 12 484 80 00
E-mail: [email protected]
Received date: May 07, 2012; Accepted date: June 18, 2012; Published date: June 20, 2012
Citation: Knapp A, Czech U, Polus A, Chojnacka M, Sliwa A, et al. (2012) Humanin Peptides Regulate Calcium Flux in the Mammalian Neuronal, Glial and Endothelial Cells under Stress Conditions. J Cell Sci Ther 3:128. doi: 10.4172/2157-7013.1000128
Copyright: © 2012 Knapp A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
"Humanin (HN) and humanin-like substances are short polypeptides that prevent neuronal cell death and dysfunction related to progression of Alzheimer?s disease. HN activates oligomeric receptor (CNFTR/WSX-1/gp130 complex) in the extracellular environment, and it is believed to interact with intracellular proteins, such as Bcl2 family. HN stimulates JAK2/STAT3 pathway that regulates apoptosis and cell death, however exact molecular mechanism of HN mediated cytoprotection remains unknown. The goal of our study was to evaluate effect HN (HNM) and HN-like peptides, which include HNG, HN10d and HN 10dV, on the intracellular calcium release in the cultured brain cells (LN18, C8D1A) and endothelial HUVECs under stress conditions. We incubated the cells with low amounts of HN (4 ?M) for 24 hours, generated cellular stress by addition of either 25 ?M β-amyloid (neuronal and glial cells) or 5 ng/mL of TNF-α (endothelial cells); and induced calcium release with 10 ?M ATP. We demonstrated that HN regulated calcium flux in all three cell types, although it was more pronounced in the endothelial than brain cells. HNM led to decreased calcium flux in C8D1A, HUVECs and LN18; HN10d ? in HUVECs, and 10dV ? in the glial cells. We hypothesized that a site of HN activity and calcium release was located in the endoplasmic reticulum (ER), in which there was slightly altered expression of selected ER-stress associated proteins upon incubation with HNs. There was no effect of the exogenous HNs on the calcium release from the isolated mitochondria. We demonstrated mRNA expression of HNM, HN10d and HN10dV in the neuronal LN18 cells; however their levels were not affected by β-amyloid treatment. It might indicate that stress conditions force HN intracellular translocation instead of change in HN gene expression. Thus it is possible that localization of HN in the ER may regulate intracellular calcium amounts, which ultimately determine fate of the cell."