title: GABA, progesterone and zona pellucida activation of PLA2 and regulation by MEK-ERK1/2 during acrosomal exocytosis in guinea pig spermatozoa.
abstract: We investigated whether GABA activates phospholipase A2 (PLA2) during acrosomal exocytosis, and if the MEK-ERK1/2 pathway modulates PLA2 activation initiated by GABA, progesterone or zona pellucida (ZP). In guinea pig spermatozoa prelabelled with [14C]arachidonic acid or [14C]choline chloride, GABA stimulated a decrease in phosphatidylcholine (PC), and release of arachidonic acid and lysoPC, during exocytosis. These lipid changes are indicative of PLA2 activation and appear essential for exocytosis since inclusion of aristolochic acid (a PLA2 inhibitor) abrogated them, along with exocytosis. GABA activation of PLA2 seems to be mediated, at least in part, by diacylglycerol (DAG) and protein kinase C since inclusion of the DAG kinase inhibitor R59022 enhanced PLA2 activity and exocytosis stimulated by GABA, whereas exposure to staurosporine decreased both. GABA-, progesterone- and ZP-induced release of arachidonic acid and exocytosis were prevented by U0126 and PD98059 (MEK inhibitors). Taken together, our results suggest that PLA2 plays a fundamental role in agonist-stimulated exocytosis and that MEK-ERK1/2 are involved in PLA2 regulation during this process.
authors.affiliation: Zhejiang Academy of Medical Science, 310013 Hangzhou, China.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Chen
authors.forename: Ya
authors.initials: Y
authors.lastname: Ni
authors.forename: Yong-Miao
authors.initials: YM
authors.lastname: Pan
authors.forename: Qi-Xian
authors.initials: QX
authors.lastname: Shi
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Yuan
authors.forename: Ai-Jun
authors.initials: AJ
authors.lastname: Chen
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Mao
authors.forename: Shu-Qing
authors.initials: SQ
authors.lastname: Yu
authors.forename: Eduardo R S
authors.initials: ER
authors.lastname: Roldan
mesh_terms: D020101:Acrosome Reaction / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry / Q000378:metabolism; D034341:Aristolochic Acids / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004789:Enzyme Activation; D005089:Exocytosis / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005260:Female; D006168:Guinea Pigs; D020935:MAP Kinase Signaling System / Q000502:physiology; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011374:Progesterone / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D013094:Spermatozoa / Q000737:chemistry / Q000378:metabolism*; D015044:Zona Pellucida / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
chemical_list: D034341:Aristolochic Acids; D004075:Diglycerides; D016718:Arachidonic Acid; D011374:Progesterone; D005680:gamma-Aminobutyric Acid; C000228:aristolochic acid I; D011493:Protein Kinase C; D048049:Extracellular Signal-Regulated MAP Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D010741:Phospholipases A; D054467:Phospholipases A2