INVESTIGADORES
MIRANDA Silvia Esther
congresos y reuniones científicas
Título:
How can progesterone modify the folding and N-glycosylation of a protein??
Autor/es:
SILVIA MIRANDA
Lugar:
Filadelfia
Reunión:
Congreso; First Glycobiology World Congress.; 2015
Institución organizadora:
OMICS International
Resumen:
How can progesterone modify the folding and N-glycosylation of a protein? Silvia E Miranda Universidad de Buenos Aires, Argentina The glycosylation pattern of many proteins can influence their physicochemical and biological properties leading to pathological consequences. Moreover, folding and glycosylation are interdependent processes. We have studied the effects of progesterone on the glycosylation of IgG and on two critical endoplasmic reticulum enzymes: The oligosaccharyltransferase complex (OST) which catalyzed the N-linked glycosylation and the UDP-Glc:Glycoprotein glucosyltransferase (UGGT) which is a central component of the Endoplasmic Reticulum (ER) glycoprotein folding quality control system. We first employed a murine hybridoma cell cultured with a physiological range of progesterone doses and analyzed: The expression of two isoforms of the OST catalytic subunit, STT3-A and STT3-B which are endowed with distinct enzymatic properties, the glycosylation pattern of the secreted IgG and the expression and activity of UGGT. We found that P4 increases IgG N-glycosylation by means of a switch of STT3 isoform expression through a progesterone-induced blocking factor (PIBF) dependent mechanism. We also described the expression and activity of two UGGT isoforms both of them differentially regulated by high P4 doses through nuclear and membrane receptors. To investigate the in vivo modulation of OST, we next employed a sound stress mouse model which increased the abortion rate due a decrease in progesterone levels and in serum glycosylated IgG. We investigated the OST isoform expression in intestine and in implantation sites. In both tissues, sound stress induced an inflammatory response and a switch of STT3 isoform expression. These findings demonstrate that progesterone can regulate both the IgG glycosylation and the glycoprotein quality control mechanism.
