Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)

Persons with Down syndrome (DS, trisomy 21) have widespread cellular protein trafficking defects. There is a paucity of data describing the intracellular transport of IgG in the context of endosomal-lysosomal alterations linked to trisomy 21. In this study, we analyzed the intracellular traffic of IgG mediated by the human neonatal Fc receptor (FcRn) in fibroblast cell lines with trisomy 21. Intracellular IgG trafficking studies in live cells showed that fibroblasts with trisomy 21 exhibit higher proportion of IgG in lysosomes (~ 10% increase), decreased IgG content in intracellular vesicles (~ 9% decrease), and a trend towards decreased IgG recycling (~ 55% decrease) in comparison to diploid cells. Amyloid-beta precursor protein (APP) overexpression in diploid fibroblasts replicated the increase in IgG sorting to the degradative pathway observed in cells with trisomy 21. The impact of APP on the expression of FCGRT (alpha chain component of FcRn) was investigated by APP knock down and overexpression of the APP protein. APP knock down increased the expression of FCGRT mRNA by ~ 60% in both diploid and trisomic cells. Overexpression of APP in diploid fibroblasts and HepG2 cells resulted in a decrease in FCGRT and FcRn expression. Our results indicate that the intracellular traffic of IgG is altered in cells with trisomy 21. This study lays the foundation for future investigations into the role of FcRn in the context of DS.

Effect of telomerization on the growth patterns of adult cutaneous diploid fibroblasts

The article describes effects of telomerization on proliferative activity in cultured cutaneous diploid fibroblasts obtained from an adult men aged 57 years. It is shown that the cells in the control culture initially divide quite actively, but starting from the 27th to the 40th passages, the rate of their division decreases and the time to reach the monolayer increases by about 2 times, and starting from the 42nd passage, the time to reach the monolayer increases by 4-10 times (up to 16-40 days). In a single case, an increase in the doubling time of control non-thelomerized cells was recorded up to 30 times (136 days). The introduction of the telomerase gene allowed cells maintain a high rate of cell division to about 45-47 passages. At the same time, the culture with the telomerase gene exceeds the control culture by 10 passages. Rate of growth the cells with telomerase gene after 48 and up to 57 passages slowed down by 10-18 times (up to 40-73 days). At the 47th passage in the control culture and at the 57th passage in the experimental culture, the cells practically stopped dividing and their number did not increase. The results show that the inclusion of the telomerase gene in adult fibroblasts does not always cancel the limit of cell divisions.

Analysis of the intracellular traffic of IgG in the context of Down syndrome (trisomy 21)

Persons with Down syndrome (DS, trisomy 21) have widespread cellular protein trafficking defects. There is a paucity of data describing the intracellular transport of IgG in the context of endosomal-lysosomal alterations linked to trisomy 21. In this study, we analyzed the intracellular traffic of IgG mediated by the human neonatal Fc receptor (FcRn) in fibroblast cell lines with trisomy 21. Intracellular IgG trafficking studies in live cells showed that fibroblasts with trisomy 21 exhibit higher proportion of IgG in lysosomes (~10% increase), decreased IgG content in intracellular vesicles (~9% decrease), and a trend towards decreased IgG recycling (~55% decrease) in comparison to diploid cells. Amyloid-beta precursor protein (APP) overexpression in diploid fibroblasts replicated the increase in IgG sorting to the degradative pathway observed in cells with trisomy 21. The impact of APP on the expression of FCGRT (alpha chain component of FcRn) was investigated by APP knock down and overexpression of the APP protein. APP knock down increased the expression of FCGRT mRNA by ~60% in both diploid and trisomic cells. Overexpression of APP in diploid fibroblasts and HepG2 cells resulted in a decrease in FCGRT and FcRn expression. Our results indicate that the intracellular traffic of IgG is altered in cells with trisomy 21. This study lays the foundation for future investigations into the role of FcRn in the context of DS.