Тип публикации: статья из журнала

Год издания: 2010

Идентификатор DOI: 10.1016/j.bbrc.2010.11.090

Ключевые слова: Hyposulfatemia, longevity, NaS1, SLC13A1, sulfate

Аннотация: Sulfate (SO₄^{2 -}) plays an important role in mammalian growth and development. The NaS1 sulfate transporter mediates renal sulfate reabsorption and regulates serum sulfate levels. Genetic sequencing of the NaS1 gene (SLC13A1) in a family with hyposulfataemia found NaS1 variants R12X and N174S. Hyposulfataemic NaS1 null (Nas1^-/-) mice were found to live longer and have less tumors in aged mice. Median life spans increased (by ≈25%) in male and female Nas1^-/- mice when compared with Nas1^+/+ mice. Increased hepatic mRNA expression of genes involved in aging: Sirt1 (by ≈60%), Cat (by ≈48%), Hdac3 (by ≈22%), Trp53 and Cd55 (by ≈36%) were detected in Nas1^-/- mice. Histological analyses of livers from 2-year-old mice revealed neoplasms in >50% of Nas1^+/+ mice but not in Nas1^-/- mice. This is the first study to identify hyposulfataemia in humans with NaS1 sequence variants. Furthermore, we identified an extended lifespan, a decreased incidence of spontaneous hepatic tumors and increased hepatic mRNA levels of 5 genes involved in aging in the Nas1^-/- mouse, indicating that NaS1 may play role in longevity and cancer. © 2010 Elsevier Inc. All rights reserved.

Журнал: Biochemical and Biophysical Research Communications

ISSN журнала: 0006291X

Издатель: Academic Press

• Markovich D. (School of Biomedical Sciences, University of Queensland, St. Lucia, Australia)
• Dawson P.A. (Mater Medical Research Institute, South Brisbane, Australia)
• Ku M.C. (School of Biomedical Sciences, University of Queensland, St. Lucia, Australia)
• Muslim D. (School of Biomedical Sciences, University of Queensland, St. Lucia, Australia)
• McWhinney A. (Pathology Department, Mater Health Services, South Brisbane, Australia)
• Heussler H.S. (School of Medicine, University of Queensland, St. Lucia, Australia)
• Bowling F.G. (Mater Children's Hospital, Mater Health Services, South Brisbane, Australia)

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