α-Klotho mice demonstrate increased expression of the non-sulfated N-glycan form of the HNK-1 glyco-epitope in kidney tissue.
The α-Klotho mouse is an animal model that prematurely exhibits phenotypes resembling human aging owing to mutation of the α-Klotho gene. Although α-Klotho mice appear normal at birth, they begin showing multiple age-associated disorders after 3-4 weeks. Meanwhile, overexpression of α-Klotho extends lifespan. Therefore, α-Klotho may be involved in the aging process. The α-Klotho protein has homology to β-glucosidase and is proposed to have glycosidase activity. However, it is unclear whether glycan alterations are present in α-Klotho mice. Here we found increased levels of the non-sulfated HNK-1 glyco-epitope in the kidneys of α-Klotho mice. This phenomenon was also observed in normal aged mice. Immunohistochemical analysis demonstrated that increased non-sulfated HNK-1 glyco-epitope appeared predominantly in the outer half of the renal cortex, where α-Klotho protein is highly expressed. To clarify the cause, the expression of glucuronyltransferase S (GlcAT-S) and the activity of β-glucuronidase were also examined. The expressions of GlcAT-S were comparable in α-Klotho mice and wild-type mice, but β-glucuronidase activity was lower in α-Klotho mice than in wild-type. These results suggest that increased non-sulfated HNK-1 epitope levels in α-Klotho mice may be due to decreased β-glucuronidase activity. Taken together, α-Klotho expression was associated with expression of the non-sulfated HNK-1 epitope.
Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan; Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; and Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Keiko
K
Akasaka-Manya
Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan; Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; and Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Hiroshi
H
Manya
Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan; Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; and Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Yasuhiko
Y
Kizuka
Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan; Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; and Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan.
Shogo
S
Oka
Molecular Glycobiology, Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo Metropolitan Geriatric Hospital and Institute of Gerontology, 35-2 Sakaecho, Itabashi-ku, Tokyo 173-0015, Japan; Department of Biological Chemistry, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan; and Department of Biological Chemistry, Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan endo@tmig.or.jp.
Tamao
T
Endo
D000818:Animals; D001921:Brain / Q000378:metabolism; D018959:CD57 Antigens / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006031:Glycosylation; D007668:Kidney / Q000201:enzymology*; D000090265:Klotho Proteins; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009928:Organ Specificity; D011134:Polysaccharides / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011956:Receptors, Cell Surface / Q000235:genetics*
D018959:CD57 Antigens; D011134:Polysaccharides; D011956:Receptors, Cell Surface; D005966:Glucuronidase; D000090265:Klotho Proteins
Glucuronyltransferase; kidney; non-sulfated HNK-1 epitope; α-Klotho; β-Glucuronidase