Oxidative stress disrupts internalization and endocytic trafficking of transferrin in a human malignant keratinocyte line

Oxidative stress is involved in epidermal cell pathology. One potential mechanism for this toxicity that has previously not been explored in epidermal cells involves modulation of endocytic trafficking and the implications that such modulation can have for altered cell function. The effects of oxida...

Full description

Saved in:
Bibliographic Details
Published in:Cell biochemistry and biophysics 2006-01, Vol.45 (2), p.177-184
Main Authors: Cheng, Julia, Vieira, Amandio
Format: Article
Language:English
Subjects:
Binding Sites
Carcinoma, Squamous Cell - metabolism
Carcinoma, Squamous Cell - pathology
Cell Line, Tumor
Cell Membrane - metabolism
Endocytosis - physiology
Humans
Hydrogen Peroxide
Keratinocytes - metabolism
Oxidative Stress
Transferrin - metabolism
Citations: Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Oxidative stress is involved in epidermal cell pathology. One potential mechanism for this toxicity that has previously not been explored in epidermal cells involves modulation of endocytic trafficking and the implications that such modulation can have for altered cell function. The effects of oxidative stress on endocytic trafficking are not well understood, particularly relating to how general or cell-type specific such effects may be. With induction of oxidative stress by hydrogen peroxide, for example, both impaired and enhanced cell-surface binding and endocytic trafficking have been reported for transferrin (Tf), a circulatory iron-carrier protein. The objective of the current study was to characterize the effect of oxidative stress on internalization and endocytic trafficking of Tf in an epidermoid cell line (A431). Evidence is presented for a significant dose-dependent impairment of cellular Tf internalization after treatment with hydrogen peroxide over a wide range of concentrations from 0.06 to 5.8 mM. Scatchard analysis of binding revealed that peroxide treatments resulted in a large decrease, more than fourfold, in the number of cell-surface Tf-binding sites (Bmax) but little change in the dissociation constant (Kd). With respect to endocytic trafficking of Tf, evidence is presented that transport of internalized transferrin back out of the cell (i.e., Tf recycling) is significantly impaired as a result of oxidative stress at all the peroxide concentrations tested. The oxidative stress-dependent changes in endocytic trafficking in these malignant human keratinocytes are compared with those reported for other cell types.
ISSN:1085-9195
1559-0283
1085-9195
DOI:10.1385/cbb:45:2:177