Klotho gene delivery suppresses oxidative stress in vivo

Abstract

Objective: Mice deficient in the klotho gene exhibit a syndrome resembling premature human aging. A recent report also suggested that klotho transgenic mice exhibited a long lifespan, which shows that klotho is an antisenescence gene. Previously, klotho has been reported to improve endothelial dysfunction, and also to have a preventive effect against oxidative stress. In the present study, we investigated the effect of klotho gene delivery on blood pressure and oxidative stress in vivo. Methods:Klotho plasmid was injected into the tail vein of mice and spontaneous hypertensive rats over 5 s. Results:Klotho gene delivery upregulated manganese superoxide dismutase protein expression and total superoxide dismutase activity in the aorta of mice compared with the control. It upregulated nitric oxide production, and downregulated lipid peroxide concentration in the serum of mice. When klotho plasmid was administered to spontaneously hypertensive rats, superoxide dismutase activity in the kidney and liver was significantly increased, and lipid peroxide concentration in the kidney and liver was significantly decreased, compared with the control. Klotho gene delivery in spontaneously hypertensive rats did not alter systolic blood pressure. Conclusion:These results suggest that klotho gene infusion into the tail vein of mice and rats has a suppressive effect against oxidative stress. These findings may provide a new insight into the therapeutic potential of klotho gene delivery in vivo to regulate oxidative stress.

Reactive Oxygen Species and Age‐Related Genes p66Shc, Sirtuin, FoxO3 and Klotho in Senescence

“…It has been shown that the formation and bioavailability of nitric oxide was decreased in old human and animals 62–65. On the other hand, it has been shown that the Klotho gene enhanced NO formation in human and animal cells 47,49. Therefore, we can hypothesize that both anti-aging genes and nitric oxide are critical factors of aging development.…”

“…Ohta et al47 investigated the effect of Klotho gene delivery on blood pressure and oxidative stress in vivo. They found that Klotho gene upregulated MnSOD expression and total SOD activity in the aorta of mice, enhanced nitric oxide production, and downregulated lipid peroxide concentration in serum of mice.…”

Reduction of cellular stress is essential for Fibroblast growth factor 1 treatment for diabetic nephropathy

“…Our previous study had also demonstrated that FGF1 treatment blocks ER stress and consequently apoptosis of DA neuron during development of Parkinson's disease (PD) . Moreover, FGF23, the FGF family, has also an anti‐oxidative stress activity . Thus, we hypothesized that FGF1‐associated glucose decreases and subsequent reduction of cellular stress is the another potential cellular molecule mechanisms mediating FGF1 treatment forDN.…”

“…17 Moreover, FGF23, the FGF family, has also an anti-oxidative stress activity. 18,19 Thus, we hypothesized that FGF1-associated glucose decreases and subsequent reduction of cellular stress is the another potential cellular molecule mechanisms mediating FGF1 treatment forDN.…”

Plasma Klotho Levels Were Inversely Associated with Subclinical Carotid Atherosclerosis in HIV-Infected Patients Receiving Combined Antiretroviral Therapy

“…24 A previous study reported that klotho gene delivery up-regulates the expression of manganese superoxide dismutase and suppresses oxidative stress in vivo. 25 In addition, circulating …”