Secreted Klotho protein in sera and CSF: implication for post‐translational cleavage in release of Klotho protein from cell membrane

Imura, Akihiro; Iwano, Akiko; Tohyama, Osamu; Tsuji, Yoshihito; Nozaki, Kazuhiko; Hashimoto, Nobuo; Fujimori, Toshihiko; Nabeshima, Yo‐ichi

doi:10.1016/j.febslet.2004.03.090

Cited by 469 publications

(247 citation statements)

References 11 publications

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“…Moreover the previous findings also agree with Derakhshanfar et al (2007) provides evidence that pre-treatment of vitamin E can prevent both the functional and histological renal changes in nephtotoxicity. Similar results found by Koh et al (2001) and Imura et al (2004) reported severely reduced production of klotho in urine and kidneys (messenger RNA and protein) by Western blot of patients with acute renal failure and klotho levels have been shown to correlate negatively with plasma creatinine levels. Also the previous results come in harmony with the results obtained by El-Far et al (2005) found the presence of significant negative correlation between GPx activity and serum creatinine level.…”

Section: Discussionsupporting

confidence: 75%

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Elgendey¹,

Hemeda²,

Sosa³

et al. 2015

American Journal of Biochemistry and Biotechnology

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Acute Renal Failure (ARF) has traditionally been defined as the abrupt and progressive loss of kidney functions resulting in the retention of urea and other nitrogenous waste products associated with interstitial inflammation, tubular injury and increasing Tumor Necrosis Factor (TNF). Mortality in patients with ARF remains high >50% in severely ill patients. Klotho gene is a new anti-aging gene. Genetic mutation of klotho gene causes multiple premature aging-like phenotypes and shortens lifespan. Klotho gene is highly expressed in the kidney and a soluble form of klotho functions as an endocrine substance that exerts multiple actions including the modulation of renal solute transport and the protection of the kidney. This study aimed to clarify the pre treatment and/or post treatment effect of vitamin E as an antioxidant on kidney functions, klotho gene expression and glutathione peroxidase-1 gene expression among rats with acute renal failure. Using glycerol as oxidative stress factor to cause acute renal failure and Real time PCR for assessment of gene expression of target gene in the control and treated groups. Our results demonstrated that the vitamin E (α tocopherol) as antioxidant factor decreased the kidney injuries as pre renal failure administer and improve kidney function as post renal failure administer. Those effects were through up regulating the Klotho as anti aging gene and the Glutathione Peroxidase (GPx-1) as antioxidant gene expression in the kidney tissue. We concluded that factors those up regulate the klotho gene expression can use as protective factors against kidney injuries and to improve kidney function in renal failure.

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Section: Discussionsupporting

confidence: 75%

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Elgendey¹,

Hemeda²,

Sosa³

et al. 2015

American Journal of Biochemistry and Biotechnology

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“…Admittedly, we cannot provide our own experimental data to support this favoured hypothesis. aKL (130 kDa) appears to result from proteolytic ectodomain clipping (10). Two members of the ' A Disintegrin and Metalloproteinase' (ADAM) family, ADAM10 and ADAM17, have been suggested as the responsible enzymes (9), and the activity of secretases (25,26) shedding the ectodomain from the integral membrane Klotho may be increased in acromegaly, either directly by GH or indirectly by factors or a proteolytic activity induced by GH.…”

Section: Discussionmentioning

confidence: 99%

“…The mechanisms leading to soluble aKL excess in the serum in active acromegaly remain unclear. Soluble aKL could arise either from a distinct transcript (24) or from ectodomain shedding of membrane Klotho (9,10,25). It remains unclear whether in acromegalics membraneassociated Klotho (mainly found in the kidneys) and soluble aKL (as detected in the serum) rise concurrently or whether elevated soluble aKL is unrelated or possibly inversely related to the abundance of plasma membrane Klotho in the kidneys -possibly resulting from enhanced enzymatic activity.…”

Section: Discussionmentioning

confidence: 99%

“…Soluble aKL attenuates insulin/insulin-like growth factor 1 (IGF1) signalling and regulates calcium homoeostasis (7,8). The extracellular domain of the membrane-bound form can be enzymatically cleaved (ectodomain shedding) and released as soluble aKL into blood, urine and cerebrospinal fluid (9,10). Recently, a sandwich ELISA for the measurement of soluble aKL was established and is now commercially available (11).…”

Section: Introductionmentioning

confidence: 99%

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Soluble α-Klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas

Neidert

Sze

Zwimpfer

et al. 2013

European Journal of Endocrinology

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Objective: Klotho is a lifespan-influencing gene expressed mainly in the kidneys. Soluble a-Klotho (aKL) is released into the circulation. In this study, we present baseline aKL serum levels of patients with acromegaly compared with controls with other pituitary adenomas and assess changes following transsphenoidal surgery. Design: Prospective controlled study. Methods: We measured soluble aKL (sandwich ELISA) and IGF1 (RIA) in sera of 14 patients (eight females and six males) with active acromegaly and in 22 control patients (13 females and nine males) operated for non-GH-producing pituitary adenomas. Immunohistochemical staining for Klotho was performed in resected adenomas and in normal pituitary tissue samples. Results: Soluble aKL was high in the acromegaly group preoperatively (median 4217 pg/ml, interquartile range (IQR) 1812-6623 pg/ml) and declined after surgery during early follow-up (2-6 days; median 645 pg/ml, IQR 550-1303 pg/ml) (P!0.001) and during late follow-up (2-3 months post-operatively; median 902 pg/ml, IQR 497-1340 pg/ml; P!0.001). In controls, preoperative soluble aKL was significantly lower than in acromegalics, 532 pg/ml (400-677 pg/ml; P!0.001). Following surgery, soluble aKL remained low during early and late follow-up -changes over time within the control group were not statistically significant. These results were independent of age, sex and kidney function. Klotho staining was equal or slightly decreased in GH-positive adenomas compared with controls. Conclusion: High soluble aKL serum levels were specific to GH-producing adenomas and decreased rapidly following adenoma removal. Thus, soluble aKL appears to be a new specific and sensitive biomarker reflecting disease activity in acromegaly. Similar Klotho staining patterns in controls and acromegalics suggest that the rise in serum aKL is caused by systemic actions of pituitary GH rather than due to increased expression of Klotho by the pituitary (adenoma).

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“…It exists in 2 forms: The transmembrane and the soluble secreted form [163] . Klotho is detected as a soluble protein in body fluids including blood, CSF and urine [164] . The highest expression of Klotho is in the kidney and the brain [6] , but it is also expressed in parathyroid gland [165] and heart [166] with less abundance.…”

Section: Sharaf El Din Uaa Et Al Stop Chronic Kidney Disease Progrementioning

confidence: 99%

Stop chronic kidney disease progression: Time is approaching

Din¹,

Salem²,

Abdulazim³

2016

WJN

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Progression of chronic kidney disease (CKD) is inevitable. However, the last decade has witnessed tremendous achievements in this field. Today we are optimistic; the dream of withholding this progression is about to be realistic. The recent discoveries in the field of CKD management involved most of the individual diseases leading the patients to end-stage renal disease. Most of these advances involved patients suffering diabetic kidney disease, chronic glomerulonephritis, polycystic kidney disease, renal amyloidosis and chronic tubulointerstitial disease. The chronic systemic inflammatory status and increased oxidative stress were also investigated. This inflammatory status influences the antisenescence Klotho gene expression. The role of Klotho in CKD progression together with its therapeutic value are explored. The role of gut as a major source of inflammation, the pathogenesis of intestinal mucosal barrier damage, the role of intestinal alkaline phosphatase and the dietary and therapeutic implications add a novel therapeutic tool to delay CKD progression.

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Secreted Klotho protein in sera and CSF: implication for post‐translational cleavage in release of Klotho protein from cell membrane

Cited by 469 publications

References 11 publications

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Factors Those Up Regulate <i>Klotho</i> and Glutathione Peroxidase-1 Gene Expression Improve Renal Function in Rats with Acute Renal Failure

Soluble α-Klotho: a novel serum biomarker for the activity of GH-producing pituitary adenomas

Stop chronic kidney disease progression: Time is approaching

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