Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells.
Klotho-mutated mice manifest multiple age-related disorders that are observed in humans. A recent study suggested that Klotho protein might function as an anti-aging hormone in mammals. Because it has been reported that apoptosis and senescence in vascular endothelial cells are closely related to the progression of atherosclerosis, we investigated Klotho's ability to interfere with apoptosis and cellular senescence in human umbilical vascular endothelial cells (HUVEC). Klotho overexpression decreased H(2)O(2)-induced apoptosis in COS-1 cells and Jurkat cells. Klotho protein also reduced H(2)O(2)- and etoposide-induced apoptosis in HUVEC. Caspase-3 and caspase-9 activity was lower in Klotho-treated HUVEC than in control cells. Senescence-associated beta-gal staining showed that Klotho protein interferes with H(2)O(2)-induced premature cellular senescence. The expression of p53 and p21 was lower in Klotho-treated cells. Our study suggests that Klotho acts as a humoral factor to reduce H(2)O(2)-induced apoptosis and cellular senescence in vascular cells.
Ikushima
Masashi
M
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Rakugi
Hiromi
H
Ishikawa
Kazuhiko
K
Maekawa
Yoshihiro
Y
Yamamoto
Koichi
K
Ohta
Junsuke
J
Chihara
Yukana
Y
Kida
Iwao
I
Ogihara
Toshio
T
D017209:Apoptosis / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D042783:Endothelial Cells / Q000166:cytology* / Q000187:drug effects*; D005966:Glucuronidase; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D000090265:Klotho Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011994:Recombinant Proteins / Q000378:metabolism
D008565:Membrane Proteins; D011994:Recombinant Proteins; D006861:Hydrogen Peroxide; D005966:Glucuronidase; D000090265:Klotho Proteins