Using light microscopic immunohistochemical methods, we found the highest levels of Klotho immunoreactivity in two brain regions: the choroid plexus, and cerebellar Purkinje cells. The purpose of the present study was to determine the precise cellular localization of Klotho in the mouse brain. The transmembrane form of the Klotho protein directly binds to multiple fibroblast growth factor receptors and modifies their ligand affinity and specificity. The extracellular domain of Klotho has an activity that increases the expression of anti-oxidant enzymes and confers resistance to oxidative stress in cultured cells and in whole animals. The klotho gene encodes a single-pass transmembrane protein whose extracellular domain is shed and released into blood, urine, and cerebrospinal fluid, potentially functioning as a humoral factor. Klotho is a putative age-suppressing gene whose over-expression in mice results in extension of life span. Khobahy, Ida Pastor, Johanne Kuro-o, Makoto Liu, Xinran Nuclear localization of Klotho in brain: an anti-aging protein The preservation of Klotho gene expression might induce the anti-oxidative stress mechanism for homeostasis of healthy human kidney independently of its general condition including age, renal function, and histological findings. Nitrotyrosine-positive bands of various sizes were observed in kidney from Klotho-deficient mice only. The expression levels of all genes were significantly higher in mice with Klotho overexpression than in wild-type mice, and those except for PRDX3 and GPX1 were significantly lower in Klotho-deficient mice than in wild-type littermate mice. Expression levels of Klotho gene were positively correlated with p53 gene, and antioxidant enzyme genes such as Catalase, superoxide dismutase 1 (SOD1), SOD2, peroxiredoxin 3 (PRDX3), and glutathione peroxidase 1 (GPX1) but not clinical parameters such as age and renal function, and pathological features such as glomerulosclerosis and interstitial fibrosis tubular atrophy. The nitrotyrosine expression level in kidney was evaluated in these animal models. In this study, we examined the relationships of Klotho and anti-oxidative stress gene expression levels in zero-hour biopsy specimens from 44 donors in kidney transplantation and verified them in animal models whose Klotho gene expression levels were varied. Other biological activities of Klotho including anti-aging effects such as protection from various cellular stress have been shown, however, the precise mechanism of these effects of Klotho gene in the healthy human kidney is not well understood. Klotho, which was originally identified as an anti-aging gene, forms a complex with fibroblast growth factor 23 (FGF23) receptor in kidney, with subsequent signaling that regulates mineral metabolism. Kimura, Takaaki Shiizaki, Kazuhiro Kurosu, Hiroshi Akimoto, Tetsu Shinzato, Takahiro Shimizu, Toshihiro Kurosawa, Akira Kubo, Taro Nanmoku, Koji Kuro-O, Makoto Yagisawa, Takashi The impact of preserved Klotho gene expression on anti-oxidative stress activity in healthy kidney.

Kid3 cardiomyocyte