KLOTHO PROTEIN AS MODERN MARKER FOR DIAGNOSTICS PROGNOSIS

KLOTHO PROTEIN AS MODERN MARKER FOR DIAGNOSTICS, PROGNOSIS, MONITORING OF THE EFFECTIVENESS OF TREATMENT Sergii Pavlov, Irina Vozna, Alexandr Vozniy State Medical University, Zaporozhye, Ukraine

• BIOLOGICAL MARKER – definition, which was introducted by National Academy of Science of the USA (2001). It entails measurement of different parameters, which characterize interaction between biological system and potentially dangerous physical, chemical and biological agents. Depending on the certain demands, biological markers can be classified according to the different signs 2

BIOLOGICAL MARKERS - Markers of the Cardiovascular Pathology, Matrix metalloproteinases (MMPs). - Markers of the central nervous system diseases, metabolic syndrome. Molecules of the endogenous cytoprotection and apoptosis. - Molecular diagnostics of the autoimmune diseases, diabetes mellitus. Cytokines. Adhesion molecules. - Markers of the GIT diseases. Molecular diagnostics of the liver, pancreas diseases. - Coagulation system monitoring, Molecular diagnostics of the anemias. Analysis of the Complement system disturbances. - Markers of the inflammation, oxidative stress. Oncomarkes. Molecular diagnostics of sepsis. Immunological markers in transplantology. - Markers of Reproduction. Prenatal diagnostics. - Hormones. - Electrolytes. - Enzymes. - Markers in fundamental and molecular biology. - NEW!!! Biomarkers in Dentistry 3

«Ideal marker» Prognosis / Risk assessment Effective diagnostics Monitoring of the treatment / dosage selection Target / Object of the Pharmacological impact Standardization of the method for detection, reproducible results 4

Klotho is an enzyme that in humans is encoded by the KL gene. This gene encodes a type-I membrane protein that is related to β-glucuronidases. Reduced production of this protein has been observed in patients with chronic renal failure (CRF), and this may be one of the factors underlying the degenerative processes (e. g. , arteriosclerosis, osteoporosis, and skin atrophy) seen in CRF. Also, mutations within this protein have been associated with ageing, bone loss and alcohol consumption. Transgenic mice that overexpress Klotho live longer than wild-type mice.

Although the vast majority of research has been based on lack of Klotho, it was demonstrated that an overexpression of Klotho in mice might extend their average life span between 19% and 31% compared to normal mice. In addition, variations in the Klotho gene (SNP Rs 9536314) are associated with both life extension and increased cognition in human populations.

Protein Klotho is Biological Marker Of Cardiovascular Pathology Protein Klotho Vit D? FGF 23 Ca 2+ Vascular Calcification

Protein Klotho is Biological Markers of the central nervous system diseases Glutamate-mediated excitotoxicity (NR 2) Protein Klotho Ca 2+ - Mitochondrial Dysfunction Modulation c-fos Modulation Bcl-2

Protein Klotho & HSP 70 are factors of endogenous cytoprotection Chaperone function of HSP 70 HSP protects protein Klotho from oxidative stress, restores corrupted structure Research of Ming-Chang, Mingium Shi, Han J. Cho et al. , May 2013, DOI : https: //doi. org/10/1038/ki. 2013. 149

HSP 70/protein Klotho Heart failure HSP 70 Protein Klotho m. RNA HSP 70 m. RNA Protein Klotho

HSP 70/protein Klotho Experemental Cerebral Ishemia HSP 70 m. RNA HSP 70 Protein Klotho m. RNA Protein Klotho

Protein Klotho. Bone tissue FGF 23 MMP Vit. D Ca 2+ Vit. D HSP 70 Protein Klotho

Protein Klotho & Dentistry Dental Health is the Main Factor Determining the Quality of Life

In fact… Expression and Synthesis of Protein Klotho In medieval times the thirtieth meant being OLD…….

GROWTH HORMONE ALSO express and synthesise Protein Klotho

30 HSP 70 Prot. Kloth Level of Protein Klotho, HSP 70 (A) and Cathelicidin (LL 37) (B) in the oral fluid of periodontitis patients before and after treatment (n=25) (30 -37 years old) ** 20 15 * 10 ** * 5 0 Control Parodontitis, Treatment 30 Catel. Prot. Kloth 25 A ** 20 ng/m 25 * 10 B ** 5 0 Control Parodontitis, Treatment

Protein Klotho, MMP 8 (A)and FGF 23 (B) in the oral fluid of patients with bone destruction and on the background of successful implantation (n=25) (30 -37 years old) 35 MMP 8 Prot. Kloth * 30 25 ng/ml 20 ** 15 ** 10 * 5 0 Control Bone destruction 30 Succes. Implant. A B FGF 23 25 ng/m 20 ** ** 15 * 10 * 5 0 Control Bone destruction Succes. Implant. Prot. Kloth

30 Vit D Prot. Kloth 25 ** ** 15 * 10 A * 5 B 0 Control Caries, Tretment 30 DPB Prot. Kloth 25 ** ** * 20 ng/ml 20 Vitamin D (A) and Vitamin D-binding protein (DBP) (B) in the oral fluid of caries patients before and after treatment (n=25) (30 -37 years old) 15 * 10 5 0 Control Caries, Tretment

Protein Klotho is not a specific marker It is marker of typical pathological processes in various systems and organs

PROSPECTS OF RESEARCH • Pathogenesis • Monitoring of the treatment / dosage selection • Target / Object of the Pharmacological correction

“Modern Molecular-biochemical Markers in Clinical and Experimental Medicine -2018” , Prague, Czech Republic OCTOBER 2018

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