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Shaher Bano Mirza, Ramin Ekhteiari Salmas, M Qaiser Fatmi, Serdar Durdagi
The Klotho is known as lifespan enhancing protein involved in antagonizing the effect of Wnt proteins. Wnt proteins are stem cell regulators, and uninterrupted exposure of Wnt proteins to the cell can cause stem and progenitor cell senescence, which may lead to aging. Keeping in mind the importance of Klotho in Wnt signaling, in silico approaches have been applied to study the important interactions between Klotho and Wnt3 and Wnt3a (wingless-type mouse mammary tumor virus (MMTV) integration site family members 3 and 3a)...
October 21, 2016: Journal of Enzyme Inhibition and Medicinal Chemistry
Jing Chen, Xiaoyan Zhang, Han Zhang, Tongqiang Liu, Hui Zhang, Jie Teng, Jun Ji, Xiaoqiang Ding
Chronic kidney disease (CKD) is a state of Klotho deficiency. The Klotho expression may be suppressed due to DNA hypermethylation in cancer cells so we have investigated the effects and possible mechanisms by which Klotho expression is regulated in human aortic smooth muscle cells (HASMCs). The vascular Klotho hypermethylation in radial arteries of patients with end-stage renal disease was described. Cultured HASMCs and 5/6-nephrectomized Sprague Dawley (SD) rats treated with indoxyl sulfate (IS) were used as in vitro and in vivo models, respectively...
2016: International Journal of Biological Sciences
Mariya Markova, Olga Pivovarova, Silke Hornemann, Stephanie Sucher, Turid Frahnow, Katrin Wegner, Jürgen Machann, Klaus Jürgen Petzke, Johannes Hierholzer, Ralf Lichtinghagen, Christian Herder, Maren Carstensen-Kirberg, Michael Roden, Natalia Rudovich, Susanne Klaus, Ralph Thomann, Rosemarie Schneeweiss, Sascha Rohn, Andreas F H Pfeiffer
BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is associated with increased risk of hepatic, cardiovascular, and metabolic diseases. High-protein diets, rich in methionine and branched chain amino acids (BCAAs), apparently reduce liver fat but may induce insulin resistance. We investigated the effects of diets high in animal protein vs plant protein, which differ in levels of methionine and BCAA, in subjects with type 2 diabetes and NAFLD. We examined levels of liver fat, lipogenic indices, markers of inflammation, serum levels of fibroblast growth factor 21 (FGF21), and activation of signaling pathways in adipose tissue...
October 17, 2016: Gastroenterology
Olga Ruiz-Andres, Maria Dolores Sanchez-Niño, Juan Antonio Moreno, Marta Ruiz-Ortega, Adrian Mario Ramos, Ana Belén Sanz, Alberto Ortiz
Chronic kidney disease (CKD) is associated to an increased risk of death, CKD progression and acute kidney injury (AKI) even from early stages, when glomerular filtration rate (GFR) is preserved. The link between early CKD and these risks is unclear, since there is no accumulation of uremic toxins. However, pathological albuminuria and kidney inflammation are frequent features of early CKD and the production of kidney protective factors may be decreased. Indeed, Klotho expression is already decreased in CKD category G1 (normal GFR)...
October 19, 2016: American Journal of Physiology. Renal Physiology
Osama Mosa, Milan Skitek, Ales Jerin
CONTEXT AND OBJECTIVE: Acute kidney injury (AKI) is still a headache for clinicians and scientists as a possible reason for increased death among intensive care unit (ICU) patients after invasive cardiac surgery. Furthermore, the diagnostic process for AKI using conventional biomarkers is not sufficient to ensure early warning of this condition because of the morbid influence of non-renal factors that definitively delay the time for the prognosis. These imposed limitations have led to significant amounts of research targeted towards identifying novel biomarkers for AKI with a sustained degree of sensitivity and specificity...
October 13, 2016: São Paulo Medical Journal, Revista Paulista de Medicina
Mohammad H Ahoor, Amir Ghorbanihaghjo, Rana Sorkhabi, Ali Kiavar
PURPOSE: Klotho is a newly discovered protein that presumably has an important role in the aging process. The goal of this research is to compare the levels of Klotho and Endothelin-1 (ET-1) in the serum and aqueous humor of patients with pseudoexfoliation syndrome (PES) and pseudoexfoliative glaucoma (PEG). PATIENTS AND METHODS: Aqueous humor and serum samples were obtained at the time of cataract surgery from 15 patients with PES, 15 patients with PEG, and 15 control patients...
October 14, 2016: Journal of Glaucoma
Zoraida Verde, Jose M Rodríguez González-Moro, Luis M Chicharro, Luis Reinoso-Barbero, Fernando Bandrés, Félix Gómez-Gallego, Catalina Santiago
Reports regarding smoking differences in α-klotho expression have provided conflicting results. In the current study we focused on the influence of smoking intensity to serum levels of the aging molecule α-klotho in healthy smokers. 40 middle aged healthy smokers without airway obstruction or restriction were selected for the analysis. Serum levels of soluble α-klotho were significantly higher in heavy smokers (P < 0.001). These results are in agreement with the possibility that α-klotho acts as anti-inflammatory molecule and strengthen the hypothesis that an increase of serum levels of α-klotho might be a compensatory response to smoking stress in healthy population...
October 17, 2016: Lung
Michael J Econs, Glenn W Irwin
No abstract text is available yet for this article.
October 13, 2016: Bone
Funda Sari, Ayca Inci, Suleyman Dolu, Hamit Yasar Ellidag, Ramazan Cetinkaya, Fettah Fevzi Ersoy
This study aims to determine fibroblast growth factor-23 and soluble α-Klotho levels in patients with autosomal dominant polycystic kidney disease. A total of 76 patients with autosomal dominant polycystic kidney disease and 32 healthy volunteers were included in the study. Serum fibroblast growth factor-23 and soluble α-Klotho levels were measured with ELISA kits. Parathyroid hormone, phosphate, calcium, creatinine, 25-hydroxyvitamin D3 levels, urinary protein to creatinine ratio and estimated glomerular filtration rate were also measured or calculated...
October 12, 2016: Journal of Investigative Medicine: the Official Publication of the American Federation for Clinical Research
Tami Rubinek, Shiri Shahmoon, Ayelet Shabtay-Orbach, Michal Ben Ami, Yael Levy-Shraga, Kineret Mazor-Aronovitch, Yonatan Yeshayahu, Ram Doolman, Rina Hemi, Hannah Kanety, Ido Wolf, Dalit Modan-Moses
CONTEXT: Klotho is an aging-modulating protein expressed mainly in the kidneys, which can be cleaved and shed to act as a circulating hormone. Several lines of evidence suggest a tight interaction between klotho and the GH-IGF-I axis. We showed previously that klotho levels are decreased in pediatric patients with growth hormone deficiency (GHD). Our aim now is to investigate the effect of GH therapy on klotho levels in these patients and to elucidate the role of IGF-1 in mediating secretion of klotho...
November 2016: Metabolism: Clinical and Experimental
Hamit Yasar Ellidag, Necat Yilmaz, Fatma Kurtulus, Ozgur Aydin, Esin Eren, Ayca Inci, Suleyman Dolu, Fatma Demet Arslan Ince, Özlem Giray, Aylin Yaman
BACKGROUND: The klotho (Klt)-fibroblast growth factor-23 (FGF-23)-vitamin D axis is the main component of calcium (Ca) and phosphorus (P) metabolisms; on the contrary, it is also secreted from the choroid plexus (CP). PURPOSE: This study is aimed at evaluating serum soluble Klt (sKlt), FGF-23, and 25-(OH)-vitamin D levels in multiple sclerosis (MS) patients. METHODS: Thirty-two relapsing-remitting MS patients (11 males and 21 females; mean age 38...
September 2016: Annals of Neurosciences
Jennifer S Yokoyama, Gabe Marx, Jesse A Brown, Luke W Bonham, Dan Wang, Giovanni Coppola, William W Seeley, Howard J Rosen, Bruce L Miller, Joel H Kramer, Dena B Dubal
Cognitive decline is a major biomedical challenge as the global population ages. Elevated levels of the longevity factor klotho suppress aging, enhance cognition, and promote synaptic plasticity and neural resilience against aging and Alzheimer's disease (AD)-related pathogenic proteins. Here, we examined the relationship between human genetic variants of KLOTHO and systemic klotho levels - and assessed neuroanatomic correlates of serum klotho in a cohort of healthy older adults. Serum klotho levels were increased with KL-VS heterozygosity, as anticipated...
October 6, 2016: Brain Imaging and Behavior
Dieter Haffner, Maren Leifheit-Nestler
Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular mortality, infections, and impaired cognitive function. It is characterized by excessively increased levels of the phosphaturic hormone fibroblast growth factor 23 (FGF23) and a deficiency of its co-receptor Klotho. Despite the important physiological effect of FGF23 in maintaining phosphate homeostasis, there is increasing evidence that higher FGF23 levels are a risk factor for mortality and cardiovascular disease. FGF23 directly induces left ventricular hypertrophy via activation of the FGF receptor 4/calcineurin/nuclear factor of activated T cells signaling pathway...
October 4, 2016: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
Qin Zhang, Shasha Yin, Lin Liu, Zhihong Liu, Wangsen Cao
Renal fibrosis is the hallmark of chronic kidney diseases (CKD) and its development and progression are significantly affected by epigenetic modifications. Rhein, a plant-derived anthraquinone, displays strong anti-fibrosis properties, but its protective mode of action remains incompletely understood. Here we explore the mechanism of Rhein anti-renal fibrosis by investigating its regulation of Klotho, a known renal anti-fibrotic protein whose suppression after renal injury reportedly involves aberrant DNA methylation...
October 5, 2016: Scientific Reports
Giuseppe Maltese, Paraskevi-Maria Psefteli, Benedetta Rizzo, Salil Srivastava, Luigi Gnudi, Giovanni E Mann, Richard C M Siow
Vascular ageing in conditions such as atherosclerosis, diabetes and chronic kidney disease, is associated with the activation of the renin angiotensin system (RAS) and diminished expression of antioxidant defences mediated by the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2). The anti-ageing hormone klotho promotes longevity and protects against cardiovascular and renal diseases. Klotho has been shown to activate Nrf2 and attenuate oxidative damage in neuronal cells, however, the mechanisms by which it protects against vascular smooth muscle cell VSMC dysfunction elicited by Angiotensin II (AngII) remain to be elucidated...
October 3, 2016: Journal of Cellular and Molecular Medicine
Rik Mencke, Jan-Luuk Hillebrands
Klotho is an anti-ageing protein that functions in many pathways that govern ageing, like regulation of phosphate homeostasis, insulin signaling, and Wnt signaling. Klotho expression levels and levels in blood decline during ageing. The vascular phenotype of Klotho deficiency features medial calcification, intima hyperplasia, endothelial dysfunction, arterial stiffening, hypertension, and impaired angiogenesis and vasculogenesis, with characteristics similar to aged human arteries. Klotho-deficient phenotypes can be prevented and rescued by Klotho gene expression or protein supplementation...
September 28, 2016: Ageing Research Reviews
Qin Zhang, Lin Liu, Wenjun Lin, Shasha Yin, Aiping Duan, Zhihong Liu, Wangsen Cao
Rhein is an anthraquinone compound isolated from the medicinal plant rhubarb and mainly used in the clinical treatment of diabetic nephropathy. Rhein exhibits various renoprotective functions, but the underlying mechanisms are not fully determined. However, its renoprotective properties recapitulate the role of Klotho, a renal-specific antiaging protein critical for maintaining kidney homeostasis. Here we explored the connections between rhein renoprotection and Klotho in a mouse model of adenine-induced chronic kidney disease...
September 27, 2016: Kidney International
Soheila Adeli, Maryam Zahmatkesh, Gholamreza Tavoosidana, Morteza Karimian, Gholamreza Hassanzadeh
Brain oxidative status is a crucial factor in the development of sporadic Alzheimer's disease (AD). Klotho, an anti-aging protein, diminishes oxidative stress by the induction of manganese superoxide dismutase (MnSOD). Thus, the substances that increase klotho expression could be considered as a potential treatment for Alzheimer's disease when the oxidative imbalance is present. Statins are suggested to up-regulate klotho expression. We examined the effect of simvastatin (5mg/kg, daily for 3weeks) on hippocampal klotho and MnSOD expression in the cognitive declined animal model induced by intracerebroventricular (ICV)-streptozotocin (STZ) administration...
January 4, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
Whitney Shatz, Domingos Ng, George Dutina, Athena W Wong, Diana Ronai Dunshee, Junichiro Sonoda, Amy Shen, Justin M Scheer
Bispecific antibodies have shown promise in the clinic as medicines with novel mechanisms of action. Lack of efficient production of bispecific IgGs, however, has limited their rapid advancement. Here, we describe a single-reactor process using mammalian cell co-culture production to efficiently produce a bispecific IgG with four distinct polypeptide chains without the need for parallel processing of each half-antibody or additional framework mutations. This method resembles a conventional process, and the quality and yield of the monoclonal antibodies are equal to those produced using parallel processing methods...
September 28, 2016: MAbs
Antero Salminen, Anu Kauppinen, Kai Kaarniranta
Fibroblast growth factor 21 (FGF21) has a significant role in the regulation of energy metabolism, e.g., in the control of systemic glucose and lipid metabolism. For instance, FGF21 enhances insulin sensitivity, increases glucose uptake, and thus can decrease serum hyperglycemia, while it also increases lipid oxidation and inhibits lipogenesis. AMP-activated protein kinase (AMPK) is a tissue energy sensor involved in maintaining the energy balance and tissue integrity. It is known that AMPK signaling generates an energy metabolic profile which displays a remarkable overlap with that of FGF21...
September 27, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
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