Anti-oxidative effect of Klotho on endothelial cells through cAMP activation |
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Authors: | Rakugi Hiromi Matsukawa Naomichi Ishikawa Kazuhiko Yang Jin Imai Michio Ikushima Masashi Maekawa Yoshihiro Kida Iwao Miyazaki Jun-ichi Ogihara Toshio |
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Institution: | (1) Department of Geriatric Medicine, Osaka University Graduate School of Medicine, 2-2 Yamadaoka (B6), Suita 565-0871, Japan;(2) Division of Stem Cell Regulation Research, Osaka University Graduate School of Medicine, 2-2 Yamadaoka (G6), Suita, Japan |
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Abstract: | Klotho, a regulatory factor implicated in countering the aging process, has been reported to ameliorate endothelial dysfunction
in vivo. To clarify whether Klotho protein directly affects endothelial cell function, we studied the effects of membrane-form
Klotho on manganese superoxide dismutase (Mn-SOD) expression and nitric oxide production in human umbilical vein endothelial
cells (HUVEC). We incubated HUVEC with conditioned medium from COS-1 cells transfected with expression vector, pCAGGS-klotho
(Klotho-CM) or a recombinant, purified 6His-tagged Klotho protein. Both Klotho-CM and 6His-tagged Klotho protein enhanced
Mn-SOD expression by approximately two-fold, partially via activation of the cAMP signaling pathway. Furthermore, Klotho-CM
increased nitric oxide production, which also contributed to the up-regulation of Mn-SOD. Using the oxidation-sensitive dye
dihydroethidium, we found that Klotho inhibited angiotensin II-induced reactive oxygen species production in HUVEC. These
findings provide new insights into the mechanisms of Klotho action and support the therapeutic potential of membrane-form
Klotho to regulate endothelial function.
Hiromi Rakugi and Naomichi Matsukawa contributed equally to this work. |
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Keywords: | Aging Angiotensin Antioxidants Endothelium Klotho |
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