RESUMO
Endometrial receptivity is essential for successful embryo implantation and pregnancy initiation and is regulated via various signaling pathways. Adiponectin, an important adipokine, may be a potential regulator of reproductive system functions. The aim of the present study was to elucidate the regulatory role of adiponectin receptor 1 (ADIPOR1) in endometrial receptivity. The endometrial receptivity between RL952 and AN3CA cell lines was confirmed using an in vitro JAr spheroid attachment model. 293T cells were transfected with control or short hairpin (sh)ADIPOR1 vectors and RL952 cells were transduced with lentiviral particles targeting ADIPOR1. Reverse transcriptionquantitative PCR and immunoblot assays were also performed. ADIPOR1 was consistently upregulated in the endometrium during the midsecretory phase compared with that in the proliferative phase and in receptive RL952 cells compared with that in nonreceptive AN3CA cells. Stable cell lines with diminished ADIPOR1 expression caused by shRNA showed reduced Ecadherin expression and attenuated in vitro endometrial receptivity. ADIPOR1 regulated AMPactivated protein kinase (AMPK) activity in endometrial epithelial cells. Regulation of AMPK activity via dorsomorphin and 5aminoimidazole4carboxamide ribonucleotide affected Ecadherin expression and in vitro endometrial receptivity. The ADIPOR1/AMPK/Ecadherin axis is vital to endometrial receptivity. These findings can help improve fertility treatments and outcomes.
Assuntos
Proteínas Quinases Ativadas por AMP , Caderinas , Endométrio , Receptores de Adiponectina , Transdução de Sinais , Receptores de Adiponectina/metabolismo , Receptores de Adiponectina/genética , Humanos , Feminino , Endométrio/metabolismo , Caderinas/metabolismo , Caderinas/genética , Proteínas Quinases Ativadas por AMP/metabolismo , Linhagem Celular , Implantação do Embrião , RNA Interferente Pequeno/metabolismo , RNA Interferente Pequeno/genética , Adulto , Aminoimidazol Carboxamida/análogos & derivados , RibonucleotídeosRESUMO
Echinochrome A (EchA) is a dark-red pigment of the polyhydroxynaphthoquinone class isolated from sea urchin Scaphechinus mirabilis. Acetylcholinesterase (AChE) inhibitors are used in the treatment of various neuromuscular disorders, and are considered as strong therapeutic agents for the treatment of Alzheimer's disease (AD). Although EchA is clinically used to treat ophthalmic diseases and limit infarct formation during ischemia/ reperfusion injury, anti-AChE effect of EchA is still unknown. In this study, we investigated the anti-AChE effect of EchA in vitro. EchA and its exhausted form which lost anti-oxidant capacity did not show any significant cytotoxicy on the H9c2 and A7r5 cells. EchA inhibited AChE with an irreversible and uncompetitive mode. In addition, EchA showed reactive oxygen species scavenging activity, particularly with nitric oxide. These findings indicate new therapeutic potential for EchA in treating reduced acetylcholine-related diseases including AD and provide an insight into developing new AChE inhibitors.