Cytochrome b561, Copper, β-Cleaved Amyloid Precursor Protein and Niemann-Pick C1 Protein are Involved in Ascorbate-Induced Release and Membrane Penetration of Heparan Sulfate from Endosomal S-Nitrosylated Glypican-1.

Cytochrome b561, Copper, β-Cleaved Amyloid Precursor Protein and Niemann-Pick C1 Protein are Involved in Ascorbate-Induced Release and Membrane Penetration of Heparan Sulfate from Endosomal S-Nitrosylated Glypican-1. Exp Cell Res. 2017 Sep 09;: Authors: Cheng F, Fransson LÅ, Mani K Abstract Ascorbate-induced release of heparan sulfate from S-nitrosylated heparan sulfate proteoglycan glypican-1 takes place in endosomes. Heparan sulfate penetrates the membrane and is transported to the nucleus. This process is dependent on copper and on expression and processing of the amyloid precursor protein. It remains unclear how exogenously supplied ascorbate can generate HS-anMan in endosomes and how passage through the membrane is facilitated. Here we have examined wild-type, Alzheimer Tg2576 and amyloid precursor protein (-/-) mouse fibroblasts and human fetal and Niemann-Pick C1 fibroblasts by using deconvolution immunofluorescence microscopy, siRNA technology and [S(35)]sulfate-labeling, vesicle isolation and gel chromatography. We found that ascorbate-induced release of heparan sulfate was dependent on expression of endosomal cytochrome b561. Formation and nuclear transport of heparan sulfate was suppressed by inhibition of β-processing of the amyloid precursor protein and formation was restored by copper (I) ions. Membrane penetration was not dependent on amyloid beta channel formation. Inhibition of endosomal exit resulted in accumulat...
Source: Experimental Cell Research - Category: Cytology Authors: Tags: Exp Cell Res Source Type: research