Journal of Glycobiology
Open Access

How can progesterone modify the folding and N-glycosylation of a protein?

Glycobiology World Congress

August 10-12, 2015 Philadelphia, USA

Silvia E Miranda

Posters-Accepted Abstracts: J Glycobiol

Abstract :

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.