Kisspeptin increases intracellular calcium concentration by protein kinase C-mediated signaling in the primary cultured neurons from rat hippocampus

Ihsan Serhatlioglu; Hande Yuksel; Emine Kacar; Sibel Ozcan; Sinan Canpolat; Mete Ozcan; Ahmet Ayar; Haluk Kelestimur

doi:10.14715/cmb/2018.64.7.10

Issue

Vol. 64 No. 7: Issue 7

Issue Published : June 12, 2018

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Kisspeptin increases intracellular calcium concentration by protein kinase C-mediated signaling in the primary cultured neurons from rat hippocampus

https://doi.org/10.14715/cmb/2018.64.7.10

Ihsan Serhatlioglu

Department of Biophysics, Faculty of Medicine, Firat University, Elazig, Turkey

Hande Yuksel

Department of Biophysics, Faculty of Medicine, Firat University, Elazig, Turkey

Emine Kacar

Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey

Sibel Ozcan

Department of Anesthesiology and Reanimation, Faculty of Medicine, Firat University, Elazig, Turkey

Sinan Canpolat

Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey

Mete Ozcan

Department of Biophysics, Faculty of Medicine, Firat University, Elazig, Turkey

Ahmet Ayar

Department of Physiology, Faculty of Medicine, Karadeniz Technical University, Trabzon, Turkey

Haluk Kelestimur

Department of Physiology, Faculty of Medicine, Firat University, Elazig, Turkey

Corresponding Author(s) : Sinan Canpolat

scanpolat@firat.edu.tr

Cellular and Molecular Biology, Vol. 64 No. 7: Issue 7
Article Published : May 30, 2018

Abstract

In addition to the fact that kisspeptin and its receptor GPR54 are well known to be abundantly expressed in the hypothalamus with suggestive roles in the initiation of puberty and similar reproductive system properties, there is also proof showing that kisspeptin might have influences on hippocampal functions. In our previous study, it was shown that kisspeptin increased free intracellular Ca2+ values ([Ca2+]i) through protein kinase C (PKC) activation in GT1-7 cells. For this reason, we examined the influences of kisspeptin on [Ca2+]i in hippocampal neurons to determine if kisspeptin shows its effects on hippocampus through the same mechanism. Hippocampal neurons were excised from the brains of fetuses on 17th embryonic day from maternal rats. The influences of kisspeptin on [Ca2+]i in hippocampal neurons were examined through in vitro calcium imaging system. The responses of [Ca2+]i to kisspeptin were quantified by the changes in 340nm/380nm ratio. Kisspeptin-10 caused [Ca2+]i transients in hippocampal neurons. The change in [Ca2+]i by 100 nM kisspeptin was prevented by pre-treating the cells in PKC inhibitor chelerythrine chloride. According to the results, kisspeptin activates intracellular calcium signaling in hippocampal neurons via the pathway that depends on PKC. The results of this study suggest that kisspeptin may have a role in hippocampal neuron functions.

Keywords

Kisspeptin Calcium Hippocampus Protein kinase C Calcium imaging.

Serhatlioglu, I., Yuksel, H., Kacar, E., Ozcan, S., Canpolat, S., Ozcan, M., Ayar, A., & Kelestimur, H. (2018). Kisspeptin increases intracellular calcium concentration by protein kinase C-mediated signaling in the primary cultured neurons from rat hippocampus. Cellular and Molecular Biology, 64(7), 56–59. https://doi.org/10.14715/cmb/2018.64.7.10

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References

Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan Gprotein coupled receptor GPR54. J Biol Chem 2001; 276: 34631.
Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, et al. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem 2001; 276: 28969-75.
Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 2001; 411: 613-7.
de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 2003; 100: 10972-76.
Seminara SB. Kisspeptin in reproduction. Semin Reprod Med. 2007; 25(5):337-43.
Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A, et al. The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem. Biophys. Res Commun 2003; 312: 1357-63.
Parhar IS, Ogawa S, Sakuma Y. Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (GPR54) duringmaturation in cichlid ï¬sh. Endocrinology 2004; 145: 3613-18.
Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc. Natl Acad Sci USA 2005; 102: 1761-66.
Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawich SK, et al. Activation of gonadotropin-releasing hormone (GnRH) neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 2005; 25: 11349-56.
Navarro VM, Fernández-Fernández R, Castellano JM, Roa J, Mayen A, Barreiro ML, et al. Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol 2004; 561: 379-86.
Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, et al. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol 2004; 16: 850-8.
Arai AC, Xia YF, Suzuki E, Kessler M, Civelli O, Nothacker HP. Cancer metastasis-suppressing peptide metastin upregulates excitatory synaptic transmission in hippocampal dentate granule cells. J Neurophysiol 2005; 94: 3648-52.
Ozcan M, Alcin E, Ayar A, Yilmaz B, Sandal S, Kelestimur H. Kisspeptin-10 elicits triphasic cytosolic calcium responses in immortalized GT1-7 GnRH neurones. Neurosci Lett 2011; 492: 55-8.
Jiang JH, He Z, Peng YL, Jin WD, Wang Z, Han RW, et al. (2015) Kisspeptin-13 enhances memory and mitigates memory impairment induced by AÎ²1-42 in mice novel object and object location recognition tasks. Neurobiol Learn Mem 123: 187-95.
Telegdy G, Adamik í. The action of kisspeptin-13 on passive avoidance learning in mice. Involvement of transmitters. Behav Brain Res. 2013; 243:300-5.
Arai AC. The role of kisspeptin and GPR54 in the hippocampus. Peptides. 2009; 30(1): 16-25.
Brailoiu GC, Dun SL, Ohsawa M, Yin D, Yang J, Chang JK, et al. KiSS-1 expression and metastin-like immunoreactivity in the rat brain. J Comp Neurol 2005; 481: 314-29.
Harms JF, Welch DR, Miele ME. KISS1 metastasis suppression and emergent pathways. Clin Exp Metastasis 2003; 20: 11-8.
Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, et al. Kisspeptin-10, a KiSS 1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci 2004; 117: 1319-28.
Yoon MJ, Lee AR, Jeong SA, Kim YS, Kim JY, Kwon YJ, et al. Release of Ca2+ from the endoplasmic reticulum and its subsequent influx into mitochondria trigger celastrol-induced paraptosis in cancer cells. Oncotarget. 2014; 5(16):6816-31.

References

Kotani M, Detheux M, Vandenbogaerde A, Communi D, Vanderwinden JM, Le Poul E, et al. (2001) The metastasis suppressor gene KiSS-1 encodes kisspeptins, the natural ligands of the orphan Gprotein coupled receptor GPR54. J Biol Chem 2001; 276: 34631.

Muir AI, Chamberlain L, Elshourbagy NA, Michalovich D, Moore DJ, Calamari A, et al. AXOR12, a novel human G protein-coupled receptor, activated by the peptide KiSS-1. J Biol Chem 2001; 276: 28969-75.

Ohtaki T, Shintani Y, Honda S, Matsumoto H, Hori A, Kanehashi K, et al. Metastasis suppressor gene KiSS-1 encodes peptide ligand of a G-protein-coupled receptor. Nature 2001; 411: 613-7.

de Roux N, Genin E, Carel JC, Matsuda F, Chaussain JL, Milgrom E. Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54. Proc Natl Acad Sci U S A 2003; 100: 10972-76.

Seminara SB. Kisspeptin in reproduction. Semin Reprod Med. 2007; 25(5):337-43.

Funes S, Hedrick JA, Vassileva G, Markowitz L, Abbondanzo S, Golovko A, et al. The KiSS-1 receptor GPR54 is essential for the development of the murine reproductive system. Biochem. Biophys. Res Commun 2003; 312: 1357-63.

Parhar IS, Ogawa S, Sakuma Y. Laser-captured single digoxigenin-labeled neurons of gonadotropin-releasing hormone types reveal a novel G protein-coupled receptor (GPR54) duringmaturation in cichlid ï¬sh. Endocrinology 2004; 145: 3613-18.

Messager S, Chatzidaki EE, Ma D, Hendrick AG, Zahn D, Dixon J, et al. Kisspeptin directly stimulates gonadotropin-releasing hormone release via G protein-coupled receptor 54. Proc. Natl Acad Sci USA 2005; 102: 1761-66.

Han SK, Gottsch ML, Lee KJ, Popa SM, Smith JT, Jakawich SK, et al. Activation of gonadotropin-releasing hormone (GnRH) neurons by kisspeptin as a neuroendocrine switch for the onset of puberty. J Neurosci 2005; 25: 11349-56.

Navarro VM, Fernández-Fernández R, Castellano JM, Roa J, Mayen A, Barreiro ML, et al. Advanced vaginal opening and precocious activation of the reproductive axis by KiSS-1 peptide, the endogenous ligand of GPR54. J Physiol 2004; 561: 379-86.

Thompson EL, Patterson M, Murphy KG, Smith KL, Dhillo WS, Todd JF, et al. Central and peripheral administration of kisspeptin-10 stimulates the hypothalamic-pituitary-gonadal axis. J Neuroendocrinol 2004; 16: 850-8.

Arai AC, Xia YF, Suzuki E, Kessler M, Civelli O, Nothacker HP. Cancer metastasis-suppressing peptide metastin upregulates excitatory synaptic transmission in hippocampal dentate granule cells. J Neurophysiol 2005; 94: 3648-52.

Ozcan M, Alcin E, Ayar A, Yilmaz B, Sandal S, Kelestimur H. Kisspeptin-10 elicits triphasic cytosolic calcium responses in immortalized GT1-7 GnRH neurones. Neurosci Lett 2011; 492: 55-8.

Jiang JH, He Z, Peng YL, Jin WD, Wang Z, Han RW, et al. (2015) Kisspeptin-13 enhances memory and mitigates memory impairment induced by AÎ²1-42 in mice novel object and object location recognition tasks. Neurobiol Learn Mem 123: 187-95.

Telegdy G, Adamik í. The action of kisspeptin-13 on passive avoidance learning in mice. Involvement of transmitters. Behav Brain Res. 2013; 243:300-5.

Arai AC. The role of kisspeptin and GPR54 in the hippocampus. Peptides. 2009; 30(1): 16-25.

Brailoiu GC, Dun SL, Ohsawa M, Yin D, Yang J, Chang JK, et al. KiSS-1 expression and metastin-like immunoreactivity in the rat brain. J Comp Neurol 2005; 481: 314-29.

Harms JF, Welch DR, Miele ME. KISS1 metastasis suppression and emergent pathways. Clin Exp Metastasis 2003; 20: 11-8.

Bilban M, Ghaffari-Tabrizi N, Hintermann E, Bauer S, Molzer S, Zoratti C, et al. Kisspeptin-10, a KiSS 1/metastin-derived decapeptide, is a physiological invasion inhibitor of primary human trophoblasts. J Cell Sci 2004; 117: 1319-28.

Yoon MJ, Lee AR, Jeong SA, Kim YS, Kim JY, Kwon YJ, et al. Release of Ca2+ from the endoplasmic reticulum and its subsequent influx into mitochondria trigger celastrol-induced paraptosis in cancer cells. Oncotarget. 2014; 5(16):6816-31.

Author biographies is not available.