title: Role of galactose in cellular senescence.
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.
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Elzi
authors.affiliation: Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, TX 78229-3900, USA.
authors.forename: Meihua
authors.initials: M
authors.lastname: Song
authors.affiliation: 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.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Shiio
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000494:pharmacology / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000502:physiology*; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005686:Galactokinase / Q000172:deficiency / Q000502:physiology; D005690:Galactose / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000494:pharmacology / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C110810:LAT protein, human; D008565:Membrane Proteins; D005686:Galactokinase; D005690:Galactose
keywords: Galactokinase; Galactose; Lysosome; Senescence; Spinster