GRP78 acts as a cAMP/PKA signaling modulator through the MC4R pathway in porcine embryonic development

by Selleckchem | Dec 17 2023

Glucose-regulated protein 78 (GRP78) binds to and stabilizes melanocortin 4 receptor (MC4R), which activates protein kinase A (PKA) by regulating G proteins. GRP78 is primarily used as a marker for endoplasmic reticulum stress; however, its other functions have not been well studied. Therefore, in this study, we aimed to investigate the function of GRP78 during porcine embryonic development. The developmental quality of porcine embryos, expression of cell cycle proteins, and function of mitochondria were evaluated by inhibiting the function of GRP78. Porcine oocytes were activated to undergo parthenogenesis, and blastocysts were obtained after 7 days of in vitro culture. GRP78 function was inhibited by adding 20 μM HA15 to the in vitro culture medium. The inhibition in GRP78 function led to a decrease in G proteins release, which subsequently downregulated the cyclic adenosine monophosphate (cAMP)/PKA pathway. Ultimately, inhibition of GRP78 function induced the inhibition of CDK1 and cyclin B expression and disruption of the cell cycle. In addition, inhibition of GRP78 function regulated DRP1 and SIRT1 expression, resulting in mitochondrial dysfunction. This study provides new insights into the role of GRP78 in porcine embryonic development, particularly its involvement in the regulation of the MC4R pathway and downstream cAMP/PKA signaling. The results suggest that the inhibition of GRP78 function in porcine embryos by HA15 treatment may have negative effects on embryo quality and development. This study also demonstrated that GRP78 plays a crucial role in the functioning of MC4R, which releases the G protein during porcine embryonic development.

Comments:

Your study explores the role of Glucose-regulated protein 78 (GRP78) in porcine embryonic development. The findings indicate that GRP78 binds to and stabilizes melanocortin 4 receptor (MC4R), thereby activating the protein kinase A (PKA) pathway through the regulation of G proteins. The study utilized HA15, an inhibitor of GRP78 function, to investigate the consequences of inhibiting GRP78 during porcine embryonic development.

The results suggest that inhibiting GRP78 function led to a decrease in G protein release, subsequently downregulating the cyclic adenosine monophosphate (cAMP)/PKA pathway. This downregulation resulted in the inhibition of CDK1 and cyclin B expression, disrupting the cell cycle. Additionally, the inhibition of GRP78 function was associated with the regulation of DRP1 and SIRT1 expression, leading to mitochondrial dysfunction.

Overall, the study provides valuable insights into the involvement of GRP78 in the regulation of MC4R and its downstream cAMP/PKA signaling pathway during porcine embryonic development. The findings suggest that inhibiting GRP78 function, as demonstrated by HA15 treatment, may negatively impact embryo quality and development. Furthermore, the study highlights the critical role of GRP78 in MC4R functioning, emphasizing its importance in porcine embryonic development.