Format

Send to

Choose Destination
Exp Gerontol. 2016 Jan;73:1-4. doi: 10.1016/j.exger.2015.11.003. Epub 2015 Nov 10.

Role of galactose in cellular senescence.

Author information

1
Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
2
Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA; Department of Biochemistry, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA. Electronic address: shiio@uthscsa.edu.

Abstract

Cellular senescence has been proposed to play critical roles in tumor suppression and organismal aging, but the molecular mechanism of senescence remains incompletely understood. Here we report that a putative lysosomal carbohydrate efflux transporter, Spinster, induces cellular senescence in human primary fibroblasts. Administration of d-galactose synergistically enhanced Spinster-induced senescence and this synergism required the transporter activity of Spinster. Intracellular d-galactose is metabolized to galactose-1-phosphate by galactokinase. Galactokinase-deficient fibroblasts, which accumulate intracellular d-galactose, displayed increased baseline senescence. Senescence of galactokinase-deficient fibroblasts was further enhanced by d-galactose administration and was diminished by restoration of wild-type galactokinase expression. Silencing galactokinase in normal fibroblasts also induced senescence. These results suggest a role for intracellular galactose in the induction of cellular senescence.

KEYWORDS:

Galactokinase; Galactose; Lysosome; Senescence; Spinster

PMID:
26547052
DOI:
10.1016/j.exger.2015.11.003
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center