Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Activation of P2X7 receptors decreases the proliferation of murine luteal cells

Jing Wang A , Shuangmei Liu B , Yijun Nie C , Bing Wu B , Qin Wu B , Miaomiao Song B , Min Tang D , Li Xiao D , Ping Xu E , Ximin Tan E , Luyin Zhang E , Gang Li D , Shangdong Liang B and Chunping Zhang D F
+ Author Affiliations
- Author Affiliations

A Department of Microbiology, School of Medicine, Nanchang University, #461 Bayi Avenue, Nanchang, Jiangxi 330006, People’s Republic of China.

B Department of Physiology, School of Medicine, Nanchang University, #461 Bayi Avenue, Nanchang, Jiangxi 330006, People’s Republic of China.

C The First Affiliated Hospital, School of Medicine, Nanchang University, #461 Bayi Avenue, Nanchang, Jiangxi 330006, People’s Republic of China.

D Department of Cell Biology, School of Medicine, Nanchang University, #461 Bayi Avenue, Nanchang, Jiangxi 330006, People’s Republic of China.

E School of Medicine, Nanchang University, #461 Bayi Avenue, Nanchang, Jiangxi 330006, People’s Republic of China.

F Corresponding author. Email: zhangcp81@gmail.com

Reproduction, Fertility and Development 27(8) 1262-1271 https://doi.org/10.1071/RD14381
Submitted: 9 October 2014  Accepted: 9 February 2015   Published: 18 March 2015

Abstract

Extracellular ATP regulates cellular function in an autocrine or paracrine manner through activating purinergic signalling. Studies have shown that purinergic receptors were expressed in mammalian ovaries and they have been proposed as an intra-ovarian regulatory mechanism. P2X7 was expressed in porcine ovarian theca cells and murine and human ovarian surface epithelium and is involved in ATP-induced apoptotic cell death. However, the role of P2X7 in corpus luteum is still unclear. The aim of this study was to investigate the role of ATP signalling in murine luteal cells and the possible mechanism(s) involved. We found that P2X7 was highly expressed in murine small luteal cells. The agonists of P2X7, ATP and BzATP, inhibited the proliferation of luteal cells. P2X7 antagonist BBG reversed the inhibition induced by ATP and BzATP. Further studies showed that ATP and BzATP inhibited the expression of cell cycle regulators cyclinD2 and cyclinE2. ATP and BzATP also inhibited the p38–mitogen-activated protein kinase (MAPK) signalling pathway. These results reveal that P2X7 receptor activation is involved in corpus luteum formation and function.

Additional keywords: ATP, corpus luteum, cyclinD2, p38MAPK, purinergic signaling.


References

Arellano, R. O., Martinez-Torres, A., and Garay, E. (2002). Ionic currents activated via purinergic receptors in the cumulus cell-enclosed mouse oocyte. Biol. Reprod. 67, 837–846.
Ionic currents activated via purinergic receptors in the cumulus cell-enclosed mouse oocyte.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XmsV2jsLk%3D&md5=5ced77da14a3292b16200729e4355f08CAS | 12193392PubMed |

Barbieri, R., Alloisio, S., Ferroni, S., and Nobile, M. (2008). Differential crosstalk between P2X7 and arachidonic acid in activation of mitogen-activated protein kinases. Neurochem. Int. 53, 255–262.
Differential crosstalk between P2X7 and arachidonic acid in activation of mitogen-activated protein kinases.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhsVWrs7nJ&md5=fc22725f306ea99c0fc57dd09d5d4712CAS | 18804898PubMed |

Baricordi, O. R., Melchiorri, L., Adinolfi, E., Falzoni, S., Chiozzi, P., Buell, G., and Di Virgilio, F. (1999). Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor. J. Biol. Chem. 274, 33206–33208.
Increased proliferation rate of lymphoid cells transfected with the P2X(7) ATP receptor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXns1aqtLc%3D&md5=5bad1e7f08d03f730a4d23706ea711cbCAS | 10559192PubMed |

Bintig, W., Baumgart, J., Walter, W. J., Heisterkamp, A., Lubatschowski, H., and Ngezahayo, A. (2009). Purinergic signalling in rat GFSHR-17 granulosa cells: an in vitro model of granulosa cells in maturing follicles. J. Bioenerg. Biomembr. 41, 85–94.
Purinergic signalling in rat GFSHR-17 granulosa cells: an in vitro model of granulosa cells in maturing follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXjvFaqt7k%3D&md5=d23945418cc1d268d7e4cbdd2e8eb1bfCAS | 19191015PubMed |

Burnstock, G., and Verkhratsky, A. (2010). Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death. Cell Death Dis. 1, e9.
Long-term (trophic) purinergic signalling: purinoceptors control cell proliferation, differentiation and death.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3M3jtVKltw%3D%3D&md5=59ff85682523c37c47dc79c380de5a7dCAS | 21364628PubMed |

Corriden, R., and Insel, P. A. (2010). Basal release of ATP: an autocrine–paracrine mechanism for cell regulation. Sci. Signal. 3, re1.
Basal release of ATP: an autocrine–paracrine mechanism for cell regulation.Crossref | GoogleScholarGoogle Scholar | 20068232PubMed |

Coutinho-Silva, R., Persechini, P. M., Bisaggio, R. D., Perfettini, J. L., Neto, A. C., Kanellopoulos, J. M., Motta-Ly, I., Dautry-Varsat, A., and Ojcius, D. M. (1999). P2Z/P2X7 receptor-dependent apoptosis of dendritic cells. Am. J. Physiol. 276, C1139–C1147.
| 1:CAS:528:DyaK1MXjsVWhsbo%3D&md5=01591dd358ae7a37306c373b2ef385fbCAS | 10329963PubMed |

Di Virgilio, F. (2007). Liaisons dangereuses: P2X(7) and the inflammasome. Trends Pharmacol. Sci. 28, 465–472.
Liaisons dangereuses: P2X(7) and the inflammasome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVWiu73M&md5=f704d91f05ac34acf26800931daaa3b5CAS | 17692395PubMed |

Faure, E., Garrouste, F., Parat, F., Monferran, S., Leloup, L., Pommier, G., Kovacic, H., and Lehmann, M. (2012). P2Y2 receptor inhibits EGF-induced MAPK pathway to stabilise keratinocyte hemidesmosomes. J. Cell Sci. 125, 4264–4277.
P2Y2 receptor inhibits EGF-induced MAPK pathway to stabilise keratinocyte hemidesmosomes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhvVGntbzP&md5=e67b4672bf6a0ea53a70777d90ccdc37CAS | 22718344PubMed |

Ferrari, D., Los, M., Bauer, M. K., Vandenabeele, P., Wesselborg, S., and Schulze-Osthoff, K. (1999). P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death. FEBS Lett. 447, 71–75.
P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXhvVClsrg%3D&md5=9c67cb696a59c336bb56e97f0bc942bfCAS | 10218585PubMed |

Gaundar, S. S., and Bendall, L. J. (2010). The potential and limitations of p38MAPK as a drug target for the treatment of haematological malignancies. Curr. Drug Targets 11, 823–833.
The potential and limitations of p38MAPK as a drug target for the treatment of haematological malignancies.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXpsFeisLg%3D&md5=55454b90bd1d1bbce5980e302a369ffaCAS | 20370645PubMed |

Grazul-Bilska, A. T., Redmer, D. A., and Reynolds, L. P. (1997). Cellular interactions in the corpus luteum. Semin. Reprod. Endocrinol. 15, 383–393.
Cellular interactions in the corpus luteum.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK1c3kt1Snug%3D%3D&md5=0f2aa6b06898a461378afd9001d2e3cdCAS | 9580947PubMed |

Hu, J. L., Xiao, L., Li, Z. Y., Wang, Q., Chang, Y., and Jin, Y. (2013). Upregulation of HO-1 is accompanied by activation of p38MAPK and mTOR in human oesophageal squamous carcinoma cells. Cell Biol. Int. 37, 584–592.
Upregulation of HO-1 is accompanied by activation of p38MAPK and mTOR in human oesophageal squamous carcinoma cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXnsVOntLk%3D&md5=a5940bd2087ad583939c9fdfc2f676cbCAS | 23412940PubMed |

Kamada, S., Blackmore, P. F., Oehninger, S., Gordon, K., and Hodgen, G. D. (1994). Existence of P2-purinoceptors on human and porcine granulosa cells. J. Clin. Endocrinol. Metab. 78, 650–656.
| 1:CAS:528:DyaK2cXitVyku7o%3D&md5=6af3019b3d8979847b9e03f456a7c615CAS | 8126137PubMed |

Li, X., Zhou, L., Feng, Y. H., Abdul-Karim, F. W., and Gorodeski, G. I. (2006). The P2X7 receptor: a novel biomarker of uterine epithelial cancers. Cancer Epidemiol. Biomarkers Prev. 15, 1906–1913.
The P2X7 receptor: a novel biomarker of uterine epithelial cancers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XhtVGktbnO&md5=166ca705364acc2c3023308d16cf2c34CAS | 17035398PubMed |

Mayo, C., Ren, R., Rich, C., Stepp, M. A., and Trinkaus-Randall, V. (2008). Regulation by P2X7: epithelial migration and stromal organisation in the cornea. Invest. Ophthalmol. Vis. Sci. 49, 4384–4391.
Regulation by P2X7: epithelial migration and stromal organisation in the cornea.Crossref | GoogleScholarGoogle Scholar | 18502993PubMed |

Miyamoto, A., Shirasuna, K., and Sasahara, K. (2009). Local regulation of corpus luteum development and regression in the cow: impact of angiogenic and vasoactive factors. Domest. Anim. Endocrinol. 37, 159–169.
Local regulation of corpus luteum development and regression in the cow: impact of angiogenic and vasoactive factors.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVKgt77O&md5=a256fc96e51a90928bc0174b5dd99030CAS | 19592192PubMed |

Niswender, G. D., Juengel, J. L., Silva, P. J., Rollyson, M. K., and McIntush, E. W. (2000). Mechanisms controlling the function and life span of the corpus luteum. Physiol. Rev. 80, 1–29.
| 1:CAS:528:DC%2BD3cXmtl2jtg%3D%3D&md5=59d93d1366f5919775f587d9881981c3CAS | 10617764PubMed |

Ortega, F., Perez-Sen, R., Delicado, E. G., and Miras-Portugal, M. T. (2009). P2X7 nucleotide receptor is coupled to GSK-3 inhibition and neuroprotection in cerebellar granule neurons. Neurotox. Res. 15, 193–204.
P2X7 nucleotide receptor is coupled to GSK-3 inhibition and neuroprotection in cerebellar granule neurons.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXhtVejurvP&md5=1b21045a34544d311d93b0d3e313166eCAS | 19384592PubMed |

Peng, J., Tang, M., Zhang, B.P., Zhang, P., Zhong, T., Zong, T., Yang, B., and Kuang, H. B. (2013). Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signalling pathway in rat luteal cells. Fertil. Steril. 99, 1436–1443e1.
Kisspeptin stimulates progesterone secretion via the Erk1/2 mitogen-activated protein kinase signalling pathway in rat luteal cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXnslCitQ%3D%3D&md5=6f6e76aa8349f672f6babf6975616198CAS | 23312234PubMed |

Santini, E., Cuccato, S., Madec, S., Chimenti, D., Ferrannini, E., and Solini, A. (2009). Extracellular adenosine 5′-triphosphate modulates insulin secretion via functionally active purinergic receptors of X and Y subtype. Endocrinology 150, 2596–2602.
Extracellular adenosine 5′-triphosphate modulates insulin secretion via functionally active purinergic receptors of X and Y subtype.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXmvVCqtLs%3D&md5=b1fac6b3fb41ad7ea7b2622b50e1ff8eCAS | 19196799PubMed |

Skarzynski, D. J., Piotrowska-Tomala, K. K., Lukasik, K., Galvao, A., Farberov, S., Zalman, Y., and Meidan, R. (2013). Growth and regression in bovine corpora lutea: regulation by local survival and death pathways. Reprod. Domest. Anim. 48, 25–37.
Growth and regression in bovine corpora lutea: regulation by local survival and death pathways.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhtlalsrrL&md5=ec6e38aa7a7ae16a41c5ad96fecc336aCAS | 23962212PubMed |

Tai, C. J., Kang, S. K., Cheng, K. W., Choi, K. C., Nathwani, P. S., and Leung, P. C. (2000). Expression and regulation of P2U-purinergic receptor in human granulosa–luteal cells. J. Clin. Endocrinol. Metab. 85, 1591–1597.
| 1:CAS:528:DC%2BD3cXisFOqu7c%3D&md5=69654fc43bbcafa503d5fdc34610889fCAS | 10770202PubMed |

Tai, C. J., Kang, S. K., Tzeng, C. R., and Leung, P. C. (2001). Adenosine triphosphate activates mitogen-activated protein kinase in human granulosa–luteal cells. Endocrinology 142, 1554–1560.
| 1:CAS:528:DC%2BD3MXitlemurY%3D&md5=838d26435be366989e97b3070d953f2fCAS | 11250936PubMed |

Tai, C. J., Chang, S. J., Leung, P. C., and Tzeng, C. R. (2004). Adenosine 5′-triphosphate activates nuclear translocation of mitogen-activated protein kinases leading to the induction of early growth response 1 and raf expression in human granulosa–luteal cells. J. Clin. Endocrinol. Metab. 89, 5189–5195.
Adenosine 5′-triphosphate activates nuclear translocation of mitogen-activated protein kinases leading to the induction of early growth response 1 and raf expression in human granulosa–luteal cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXovVemtr4%3D&md5=90b51fd420881b56273a76d9ccc043c5CAS | 15472225PubMed |

Tai, C. J., Chang, S. J., Chien, L. Y., Leung, P. C., and Tzeng, C. R. (2005). Adenosine triphosphate induces activation of caspase-3 in apoptosis of human granulosa–luteal cells. Endocr. J. 52, 327–335.
Adenosine triphosphate induces activation of caspase-3 in apoptosis of human granulosa–luteal cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXntVWrsrc%3D&md5=40284c763f85177d755d77ace4991650CAS | 16006727PubMed |

Vázquez-Cuevas, F. G., Juarez, B., Garay, E., and Arellano, R. O. (2006). ATP-induced apoptotic cell death in porcine ovarian theca cells through P2X7 receptor activation. Mol. Reprod. Dev. 73, 745–755.
ATP-induced apoptotic cell death in porcine ovarian theca cells through P2X7 receptor activation.Crossref | GoogleScholarGoogle Scholar | 16541451PubMed |

Vázquez-Cuevas, F. G., Cruz-Rico, A., Garay, E., García-Carrancá, A., Pérez-Montiel, D., Juárez, B., and Arellano, R. O. (2013). Differential expression of the P2X7 receptor in ovarian surface epithelium during the oestrous cycle in the mouse. Reprod. Fertil. Dev. 25, 971–984.
Differential expression of the P2X7 receptor in ovarian surface epithelium during the oestrous cycle in the mouse.Crossref | GoogleScholarGoogle Scholar | 23050672PubMed |

Weihs, A. M., Fuchs, C., Teuschl, A. H., Hartinger, J., Slezak, P., Mittermayr, R., Redl, H., Junger, W. G., Sitte, H. H., and Runzler, D. (2014). Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation. J. Biol. Chem. 289, 27090–27104.
Shock wave treatment enhances cell proliferation and improves wound healing by ATP release-coupled extracellular signal-regulated kinase (ERK) activation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhs1eiurvI&md5=853ab4b68ae81837acc392107f2d6319CAS | 25118288PubMed |

Xu, S., Wen, H., and Jiang, H. (2012). Urotensin II promotes the proliferation of endothelial progenitor cells through p38 and p44/42 MAPK activation. Mol. Med. Rep. 6, 197–200.
| 1:CAS:528:DC%2BC38XovFSmtrc%3D&md5=46e32f92213d5bed4d3c5cfe3f416f7cCAS | 22552405PubMed |

Yang, D., Elner, S. G., Clark, A. J., Hughes, B. A., Petty, H. R., and Elner, V. M. (2011). Activation of P2X receptors induces apoptosis in human retinal pigment epithelium. Invest. Ophthalmol. Vis. Sci. 52, 1522–1530.
Activation of P2X receptors induces apoptosis in human retinal pigment epithelium.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXmslWjs78%3D&md5=367fa427f5618246516799924c45f4acCAS | 21071745PubMed |

Yoon, M. J., Lee, H. J., Lee, Y. S., Kim, J. H., Park, J. K., Chang, W. K., Shin, H. C., and Kim, D. K. (2007). Extracellular ATP is involved in the induction of apoptosis in murine haematopoietic cells. Biol. Pharm. Bull. 30, 671–676.
Extracellular ATP is involved in the induction of apoptosis in murine haematopoietic cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXls1aktLw%3D&md5=f0b9d47f8f2271255a656f3905941578CAS | 17409500PubMed |

Yoshioka, S., Abe, H., Sakumoto, R., and Okuda, K. (2013). Proliferation of luteal steroidogenic cells in cattle. PLoS ONE 8, e84186.
Proliferation of luteal steroidogenic cells in cattle.Crossref | GoogleScholarGoogle Scholar | 24386349PubMed |

Zhang, X., Meng, L., He, B., Chen, J., Liu, P., Zhao, J., Zhang, Y., Li, M., and An, D. (2009). The role of P2X7 receptor in ATP-mediated human leukaemia cell death: calcium influx-independent. Acta Biochim. Biophys. Sin. (Shanghai) 41, 362–369.
The role of P2X7 receptor in ATP-mediated human leukaemia cell death: calcium influx-independent.Crossref | GoogleScholarGoogle Scholar | 19430700PubMed |