Klotho protein: Its role in aging and central nervous system pathology

Boksha, Irina S.; Прохорова, Т. А.; Savushkina, Olga K.; Tereshkina, Elena B.

doi:10.1134/s0006297917090024

Cited by 23 publications

(10 citation statements)

References 98 publications

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“…Klotho is firstly discovered as an anti-aging gene and knock-out of klotho accelerates aging in mice (Kurosu et al, 2005). Subsequently, accumulating evidence support that klotho has a wide range of biological effects, including anti-aging, anti-apoptosis, calcium and phosphorus metabolism, anti-carcinogenesis, and anti-oxidation (Abraham et al, 2016;Boksha et al, 2017). In our study, overexpression of klotho exhibited a significant anti-oncogenic role in osteosarcoma.…”

Section: Discussionsupporting

confidence: 56%

Overexpression of klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo

2020

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Klotho is originally discovered as an anti-aging gene and knock-out of klotho accelerates aging in mice. Subsequent studies support the anti-carcinogenesis role of klotho in a variety of human malignancies. The present study investigated the role of klotho on growth and metastasis of osteosarcoma cells. The osteosarcoma cells were transduced with lentivirus particles encoding klotho or scramble control. The reconstructed osteosarcoma cells were injected into the femoral medullary cavity of nude mice to establish a xenograft animal model. The anti-tumor properties of klotho were evaluated in terms of tumor growth, apoptosis, glycogen production, and pulmonary metastasis. Lentivirus-mediated overexpression of klotho significantly decreased tumor volume and weight in osteosarcoma mice. Determination of PCNA and Ki67 expression revealed that overexpression of klotho inhibited cell proliferation in tumor tissues obtained from osteosarcoma xenografts. PAS staining also showed that overexpression of klotho significantly decreased the production of glycogen in osteosarcoma. Moreover, TUNEL positive cells were significantly increased after lentivirus-mediated overexpression of klotho. Furthermore, lentivirus-mediated upregulation of klotho reduced the number of pulmonary metastatic lesions in mice compared to control mice. These findings demonstrated that elevated klotho could inhibit osteosarcoma cell growth and pulmonary metastasis in vivo, suggesting that klotho may be a valuable therapeutic target for osteosarcoma.

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Section: Discussionsupporting

confidence: 56%

Overexpression of klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo

2020

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“…The Klotho gene is mainly expressed in brain and kidney tissues ( 21 , 22 ). In animal models of kidney diseases, it has been demonstrated that the expression level of Klotho protein is reduced ( 23 ).…”

Section: Discussionmentioning

confidence: 99%

Aerobic exercise‑stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney

Luan

et al. 2018

Exp Ther Med

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Aerobic exercise induces many adaptive changes in the whole body and improves metabolic characteristics. Klotho, an anti-aging gene, is mainly expressed in the brain and kidney. The roles of Klotho in the brain and kidney during aerobic exercise remain largely unknown. The present study aimed to determine whether aerobic exercise could influence the expression of Klotho, decrease reactive oxygen species (ROS) and prolong life span. Sprague Dawley rats were exercised on a motor treadmill. Klotho mRNA and protein expression levels in rat brain and kidney tissues were examined using reverse transcription-quantitative polymerase chain reaction and western blotting, respectively. ROS production was detected following intermittent aerobic exercise (IAE) or continuous aerobic exercise (CAE). Kaplan-Meier curve analysis demonstrated that aerobic exercise significantly improved rat survival (P<0.001). The ROS levels in rat brain and kidney tissues were decreased in the aerobic exercise groups compared with the control group (P<0.05). In addition, Klotho mRNA and protein expression levels were increased significantly following aerobic exercise compared with controls (P<0.05). There was no significant difference between the IAE and CAE groups in any experiments (P>0.05). These results suggest that aerobic exercise-stimulated Klotho upregulation extends the life span by attenuating the excess production of ROS in the brain and kidney. As Klotho exhibits a potential anti-aging effect, promoting Klotho expression through aerobic exercise may be a novel approach for the prevention and treatment of aging and aging-related diseases.

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“…Chemokine ligand 11 and β‐2 microglobulin may accelerate brain aging (Villeda et al,; Smith et al, ). Klotho proteins have been shown to protect against senescence by enzymatically activating many intracellular signaling pathways including the insulin signaling (Xu and Sun, ; Boksha et al, ). Klotho acts in the forms of a membrane‐spanning protein and a secreted protein.…”

Section: Resultsmentioning

confidence: 99%

Calmodulin‐like skin protein suppresses the increase in senescence‐associated β‐galactosidase induced by hydrogen peroxide or ultraviolet irradiation in keratinocytes

Yusuke

Miyachi

Nawa

et al. 2019

Cell Biology International

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Calmodulin‐like skin protein (CLSP) is a secreted peptide that is produced by skin keratinocytes and some related epithelial cells. It has previously been shown that CLSP is recruited via the bloodstream into the central nervous system where it likely exerts a neuroprotective effect against toxicity related to Alzheimer's disease (AD) by binding to the heterotrimeric humanin receptor and activating intracellular survival signaling. However, it remains to be elucidated whether secreted CLSP shows a protective effect in the skin tissues. In the current study, using primary keratinocytes treated with hydrogen peroxide (H2O2) or exposed to ultraviolet (UV) irradiation as senescence models of keratinocytes, we addressed whether CLSP affects senescence in skin keratinocytes. We found that CLSP expression was upregulated by H2O2 or UV in keratinocytes. Furthermore, co‐incubation with recombinant CLSP reduced the increase in senescence‐associated β‐galactosidase‐positivity in keratinocytes that were induced by H2O2 or UV. These results suggest that CLSP may function as a senescence‐suppressing factor in keratinocytes.

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Klotho protein: Its role in aging and central nervous system pathology

Cited by 23 publications

References 98 publications

Overexpression of klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo

Overexpression of klotho suppresses growth and pulmonary metastasis of osteosarcoma in vivo

Aerobic exercise‑stimulated Klotho upregulation extends life span by attenuating the excess production of reactive oxygen species in the brain and kidney

Calmodulin‐like skin protein suppresses the increase in senescence‐associated β‐galactosidase induced by hydrogen peroxide or ultraviolet irradiation in keratinocytes

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