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Volume 3
Current Research: Integrative Medicine
Chronic Diseases 2018
July 16-17, 2018
Page 28
Notes:
Chronic Diseases
July 16-17, 2018 Berlin, Germany
2
nd
International Conference on
Vagharsh Khachikyan, Curr Res Integr Med 2018, Volume 3
DOI: 10.4172/2529-797X-C1-001
The dysfunction of cGMP-activatedNa
+
/Ca
2+
exchange controlling cell hydration is a primarymechanism
for cell pathology
O
ver-hydration of cells is a hallmark for early detection of cell pathology. Na
+
/K
+
-ATPase, having a central role in metabolic
regulation of cell hydration, has three catalytic isoforms with different affinities to ouabain and functional activities.
Among these isoforms, the α3 isoform, with the highest affinity to ouabain, isn’t involved in ion-transporting process and has
an intracellular signaling function. It is known that α3 isoforms of Na
+
/K
+
-ATPase, which are absent in non-excitable cells
of healthy animals, are highly expressed in cell pathology, including cancerous cells. On the basis of this, the expression of
these isoforms is considered as one of the early hallmarks for cell pathology). It has also been shown that α3 isoform, which
is absent in non-excitable cells of healthy animals, appears in non-cancerous tissues of women with breast cancer, as well as
in all non-excitable tissues of mice carrying sarcoma-180 tumor. Moreover, it has also been shown that this expression of
α3 isoform is accompanied by cell hydration. On the basis of these data, it has been hypothesized that the dysfunction of
intracellular signaling system controlling cell hydration could serve as a primary mechanism for carcinogenesis. To check
this hypothesis, in non-excitable tissues of healthy and sarcoma-180 carrying mice (including tumor tissues), dose-dependent
ouabain effects on Na
+
/K
+
-pump activity, cell hydration, intracellular cyclic nucleotides (cGMP and cAMP), glycolysis rate
(lactate concentration in blood and lactate dehydrogenase activity), membrane permeability for protons, Na
+
/H
+
, Na
+
/Ca
2+
exchange and cell proliferation by means of electrophysiological, isotope, immunoassay andmicroscopic methods were studied.
These studies have brought us to conclusion that the dysfunction of α3 isoform-dependent cGMP-activated Na
+
/Ca
2+
exchange
in forward mode, which controls Na
+
/K
+-
pump activity, cell hydration, membrane permeability for Na
+
and Ca
2+
, glycolysis
activity and cell proliferation, is a primary mechanism for generation of cell over-hydration and Warburg phenomena leading
to carcinogenesis. Therefore, α3 isoform-dependent cGMP-activated Na
+
/Ca
2+
exchange in forward mode has been suggested
as a novel therapeutic target for early stage of carcinogenesis.
Biography
Vagharsh Khachikyan has received his PhD in Cancer Therapy at Yerevan State Medical University. Currently, he is a Physician at National Center of Oncology named
after V. A. Fanarjyan and a Senior Scientist and Lecturer at UNESCO Chair in Life Sciences at Life Sciences International Postgraduate Educational Center. He also con-
ducts lectures on oncology at UNESCO Chair in Life Sciences. His research includes the study of the dysfunction of intracellular signaling system responsible for cancer
generation. He has participated in a number of international trainings and conferences.
info@biophys.amVagharsh Khachikyan
International Postgraduate Educational Center, Armenia