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16 July 2014 Activation of 5′ Adenosine Monophosphate-Activated Protein Kinase Blocks Cumulus Cell Expansion Through Inhibition of Protein Synthesis During In Vitro Maturation in Swine
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Abstract

The serine/threonine kinase 5′ adenosine monophosphate-activated protein kinase (AMPK), a heterotrimeric protein known as a metabolic switch, is involved in oocyte nuclear maturation in mice, cattle, and swine. The present study analyzed AMPK activation in cumulus cell expansion during in vitro maturation (IVM) of porcine cumulus-oocyte complexes (COC). 5-Aminoimidazole-4-carboxamide-1-beta-d-ribofuranoside (AICAR) is a well-known activator of AMPK. It inhibited oocyte meiotic resumption in COC. Moreover, cumulus cell expansion did not occur in the presence of AICAR, demonstrating its marked impact on cumulus cells. Activation of AMPK was supported by AICAR-mediated phosphorylation of alpha AMPK subunits. Furthermore, the presence of AICAR increased glucose uptake, a classical response to activation of this metabolic switch in response to depleted cellular energy levels. Neither nuclear maturation nor cumulus expansion was reversed by glucosamine, an alternative substrate in hyaluronic acid synthesis, through the hexosamine biosynthetic pathway, which ruled out possible depletion of substrates. Both increased gap junction communication and phosphodiesterase activity in COC are dependent on protein synthesis during the initial hours of IVM; however, both were inhibited in the presence of AICAR, which supports the finding that activation of AMPK by AICAR mediated inhibition of protein synthesis. Moreover, this protein synthesis inhibition was equivalent to that of the well-known protein synthesis inhibitor cycloheximide, as observed on cumulus expansion and protein concentration. Finally, the phosphorylation level of selected kinases was investigated. The pattern of raptor phosphorylation is supportive of activation of AMPK-mediated inhibition of protein synthesis. In conclusion, AICAR-mediated AMPK activation in porcine COC inhibited cumulus cell expansion and protein synthesis. These results bring new considerations to the importance of this kinase in ovarian physiology and to the development of new oocyte culture medium.

Nicolas Santiquet, Maxime Sasseville, Martin Laforest, Christine Guillemette, Robert B. Gilchrist, and François J. Richard "Activation of 5′ Adenosine Monophosphate-Activated Protein Kinase Blocks Cumulus Cell Expansion Through Inhibition of Protein Synthesis During In Vitro Maturation in Swine," Biology of Reproduction 91(2), (16 July 2014). https://doi.org/10.1095/biolreprod.113.116764
Received: 13 December 2013; Accepted: 1 June 2014; Published: 16 July 2014
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