Role of Cardiac Glycosides in Regulation of the Growth of Retinal Tissue Explants

Lopatina, E. V.; Karetsky, A. V.; Penniyaynen, V. A.; Виноградова, Т. В.

doi:10.1007/s10517-009-0384-7

Cited by 8 publications

(3 citation statements)

References 8 publications

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“…The butanol extract contained flavonoids with retardation values similar to those of the flavonoids in the EtOAc extract. The pharmacology of cardiac glycosides involves a complex set of direct and indirect effects (Katzung & Parmely, 2001;Lopatina, 2008). Their most important effect is to enhance the force and velocity of myocardial contraction (positive inotropic effect).…”

Section: Discussionmentioning

confidence: 99%

Extraction and phytochemical investigation ofCalotropis procera: Effect of plant extracts on the activity of diverse muscles

Moustafa

Ahmed

Nabil

et al. 2010

Pharmaceutical Biology

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Section: Discussionmentioning

confidence: 99%

Extraction and phytochemical investigation ofCalotropis procera: Effect of plant extracts on the activity of diverse muscles

Moustafa

Ahmed

Nabil

et al. 2010

Pharmaceutical Biology

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“…Retinoschisin has a known protective effect on the survival of outer retinal cells, 33 , 34 but the effect of cardiac glycosides appears to be concentration dependent. Whereas low levels (10 −11 to 10 −13 M) of cardiac glycosides were reported to stimulate retinal explant growth, 40 higher concentrations significantly disrupted retinal integrity and functionality. 41 – 44 Furthermore, treatment of heart diseases with cardiac glycosides can have detrimental repercussions on the patients’ vision.…”

Section: Discussionmentioning

confidence: 94%

Retinoschisin and Cardiac Glycoside Crosstalk at the Retinal Na/K-ATPase

Schmid

Plössl

Schmid

et al. 2020

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. Mutations in the RS1 gene, which encodes retinoschisin, cause X-linked juvenile retinoschisis, a retinal dystrophy in males. Retinoschisin specifically interacts with the retinal sodium-potassium adenosine triphosphatase (Na/K-ATPase), a transmembrane ion pump. Na/K-ATPases also bind cardiac glycosides, which control the activity of the pump and have been linked to disturbances in retinal homeostasis. In this study, we investigated the crosstalk between retinoschisin and cardiac glycosides at the retinal Na/K-ATPase and the consequences of this interplay on retinal integrity. METHODS. The effect of cardiac glycosides (ouabain and digoxin) on the binding of retinoschisin to the retinal Na/K-ATPase was investigated via western blot and immunocytochemistry. Also, the influence of retinoschisin on the binding of cardiac glycosides was analyzed via enzymatic assays, which quantified cardiac glycoside-sensitive Na/K-ATPase pump activity. Moreover, retinoschisin-dependent binding of tritium-labeled ouabain to the Na/K-ATPase was determined. Finally, a reciprocal effect of retinoschisin and cardiac glycosides on Na/K-ATPase localization and photoreceptor degeneration was addressed using immunohistochemistry in retinoschisin-deficient murine retinal explants. RESULTS. Cardiac glycosides displaced retinoschisin from the retinal Na/K-ATPase; however, retinoschisin did not affect cardiac glycoside binding. Notably, cardiac glycosides reduced the capacity of retinoschisin to regulate Na/K-ATPase localization and to protect against photoreceptor degeneration. CONCLUSIONS. Our findings reveal opposing effects of retinoschisin and cardiac glycosides on retinal Na/K-ATPase binding and on retinal integrity, suggesting that a fine-tuned interplay between both components is required to maintain retinal homeostasis. This observation provides new insight into the mechanisms underlying the pathological effects of cardiac glycoside treatment on retinal integrity.

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“…The interaction ouabain with Na + ,K + -ATPase leads to activation of Src kinases, the formation of the receptor-tyrosinekinase complex and the launch of various signaling cascades, including that leading to increase of reactive oxygen species (Aperia 2007). Being a signal transducer, Na + ,K + -АТPase controls cell growth and proliferation (Kipenko et al 2009;Lopatina et al 2005Lopatina et al , 2008bPanniiaĭnen et al 2003;Schoner 2002aSchoner , 2002bXie 2001). In low concentrations ouabain increase the synthesis of proteins, cell size, stimulates the process of cell division.…”

Section: R a F Tmentioning

confidence: 99%

Modulation of the transducer function of Na⁺,K⁺-ATPase: new mechanism of heart remodeling

Lopatina

Kipenko

Pasatetskaya

et al. 2016

Can. J. Physiol. Pharmacol.

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Endogenous digitalis-like factors were found in the mammalian and human blood. It was the starting point for the elucidation of the new non-pumping function of the Na,K-ATPase. It was previously well known that Na,K-ATPase is a pharmacological target receptor for cardiac glycosides (J.C. Skou. 1957. Biochim. Biophys. Acta, 23: 394-401). We have investigated the trophotropic effects of such agents as ouabain, epinephrine, norepinephrine, atenolol, and comenic acid using the organotypic tissue culture combined with the reconstruction of optical cross sections and confocal microscopy. It was shown that the growth zone of organotypic culture forms a multidimensional structure. Our results indicate that the cardiac glycoside ouabain applied in endogenous concentrations (10, 10 mol/L) can modulate transducer function of Na,K-ATPase and control the cell growth and proliferation. It was also shown that Src-kinase is involved in "endogenous" ouabain activated intracellular pathways as a series unit. Epinephrine (10-10 mol/L) and comenic acid (10-10 mol/L) were demonstrated to modulate the growth of 10- to 12-day-old chicken embryo cardiac tissue explants in a dose-dependent manner. Epinephrine and comenic acid regulate growth and proliferation of the cardiac tissue via receptor-mediated modulation Na,K-ATPase as a signal transducer. The trophotropic effects of the investigated agents specifically control the heart remodeling phenomenon.

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Role of Cardiac Glycosides in Regulation of the Growth of Retinal Tissue Explants

Cited by 8 publications

References 8 publications

Extraction and phytochemical investigation ofCalotropis procera: Effect of plant extracts on the activity of diverse muscles

Extraction and phytochemical investigation ofCalotropis procera: Effect of plant extracts on the activity of diverse muscles

Retinoschisin and Cardiac Glycoside Crosstalk at the Retinal Na/K-ATPase

Modulation of the transducer function of Na⁺,K⁺-ATPase: new mechanism of heart remodeling

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Role of Cardiac Glycosides in Regulation of the Growth of Retinal Tissue Explants

Cited by 8 publications

References 8 publications

Extraction and phytochemical investigation ofCalotropis procera: Effect of plant extracts on the activity of diverse muscles

Extraction and phytochemical investigation ofCalotropis procera: Effect of plant extracts on the activity of diverse muscles

Retinoschisin and Cardiac Glycoside Crosstalk at the Retinal Na/K-ATPase

Modulation of the transducer function of Na+,K+-ATPase: new mechanism of heart remodeling

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Modulation of the transducer function of Na⁺,K⁺-ATPase: new mechanism of heart remodeling