CYSTAMINE AND CYSTINE SUPPRESS NA+ TRANSPORT IN FROG SKIN EPITHELIUM
Abstract and keywords
Abstract (English):
Amphibian skin and other isolated epithelial systems are classical model objects for studying the mechanisms of transepithelial ion transport. Na+ transport in osmoregulatory epithelium is a complex, multicomponent system, which involves Na+ transporting proteins and signaling cascades localized in various cell membranes. The protein components of this system may be a target for oxidative stress. At the same time, the effect of oxidizing and reducing agents on Na+ transport in native epithelial systems, such as frog skin epithelium, practically has not been studied. Using voltage-clamp technique the effect of disulfide-containing oxidizing agents cystine and cystamine on Na+ transport in frog skin was investigated. It has been shown for the first time that the treatment of the skin of the Rana temporaria frog with cystamine or cystine at a concentration of 10 μg/ml suppresses the transepithelial Na+ transport. It was also found that the preincubation with dithiothreitol, which reduces disulfide bonds in proteins, prevents the inhibitory effect of cystamine and cystine. The obtained results indicate that Na+ transport in the frog skin is sensitive to oxidative stress and is modulated by disulfide-containing oxidizing agents, such as cystamine or cystine, and also that the effect of cystamine and cystine on Na+ transport in the frog skin epithelium is mediated by their interaction with functionally important cysteine residues of Na+-transporting proteins.

Keywords:
Na+ transport, cystamine, cystine, dithiothreitol, frog skin epithelium
Text
Publication text (PDF): Read Download
References

1. Natochin Yu.V. Fundamentals of kidney physiology. L.: Nauka, 1982, 184 p. (In Russ.)]

2. Benos D.J., Stanton B.A. Functional domeins within the degenerin/epitelial sodium channel (Deg/ENaC) superfamily of ion channels. J. Physiol., 1999, vol. 520, pp. 631-644.

3. Firsov D., Robert-Nicoud M., Gruender S., Schild L., Rossier B.C. Mutational analysis of cysteine-rich domain of the epithelium sodium channel (ENaC): Identification of cysteines essential for channel expression at the cell surface. J. Biol. Chem., 1999, vol. 274, pp. 2743-2749.

4. Kellenberger S., Gautschi I., Pfister Y., Schild L. Intracellular thiol-mediated modulation of epithelial sodium channel activity. J. Biol. Chem., 2005, vol. 280, pp. 7739-7747.

5. Koefoed-Johnsen V., Ussing H.H. The nature of the frog skin potential. Acta. Physiol. Scand., 1958, vol. 42, pp. 298-308.

6. Boldyrev A.A., Bulygina E.R. Na/K-ATPase and oxidative stress. Ann. N.Y. Acad. Sci., 1997, vol. 834, pp. 666-668.

7. Coor C., Salmon R.F., Quigley R., Marver D., Baum M. Role of adenosine triphosphate (ATP) and NaKATPase in the inhibiton of proximal tubule transport with intracellular cystine loading. J. Clin. Invest., 1991, vol. 87, pp. 955-961.

8. Lesort M., Lee M., Tucholski J., Johnson G.V.W. Cystamine inhibits caspase activity. J. Biol. Chem., 2003, vol. 278, pp. 3825-3830.

9. Paul B.D., Snyder S.H. Therapeutic applications of cysteamine and cystamine in neurodegenerative and neuropsychiatric diseases. Front. Neurol., 2019, vol. 10, art. 1315.

10. Wagner C.A., Lang F., Broer S. Function and structure of heterodimeric amino acid transporters. Amer. J. Physiol., 2001, vol. 281, pp. C1077-C1093.

11. Sheng S.H., Li J.Q., McNulty K.A., Kieber-Emmons T., Kleyman T.R. Epithelial sodium channel pore region. Structure and role in gating. J. Biol. Chem., 2001, vol. 276, pp. 1326-1334.

12. Krumm P., Giraldez T., Alvarez de la Rosa D., Clauss W.G., Fronius M., Althaus M. Thiol-reactive compounds from garlic inhibit the epithelial sodium channel (ENaC). Bioorg. Med. Chem., 2012, vol. 20, pp. 3979-3984.

13. Waag T., Gelhaus C., Rath J., Stich A., Leippe M., Schirmeister T. Allicin and derivates are cysteine protease inhibitors with antiparasitic activity. Bioorg. Med. Chem. Lett., 2010, vol. 20, pp. 5541-5543.

14. Kleyman T.R., Carattino M.D., Hughey R.P. ENaC at the cutting edge: regulation of epithelial sodium channels by proteases. J. Biol. Chem., 2009, vol. 284, pp. 20447-20451.

15. Rossier B.C., Stutts M.J. Activation of the epithelial sodium channel (ENaC) by serine proteases. Annu. Rev. Physiol., 2009, vol. 71, pp. 361-379.

16. Bengrine A., Li J., Hamm L.L., Awayda M.S. Indirect activation of the epithelial Na+ channel by trypsin. J. Biol. Chem., 2007, vol. 282, pp. 26884-26896.

17. Garcia-Caballero A., Ishmael S.S., Dang Y., Gillie D., Bond J.S., Milgram S.L., Stutts M.J. Activation of the epithelial sodium channel by the metalloprotease meprin β-subunit. Channels (Austin), 2011, vol. 5, pp. 14-22.

18. Haerteis S., Krappitz M., Bertog M., Krappitz A., Baraznenok V., Henderson I., Lindstrom E., Murphy J.E., Bunnett N.W., Korbmacher C. Proteolytic activation of the epithelial sodium channel (ENaC) by the cysteine protease cathepsin-S. Eur. J. Physiol., 2012, vol. 464, pp. 353-365.

19. Brix K., Dunkhorst A., Mayer K., Jordans S. Cysteine cathepsins: cellular roadmap to different functions. Biochimie, 2008, vol. 90, pp. 194-207.

20. Kirschke H., Wiederanders B., Bromme D., Rinne A. Cathepsin S from bovine spleen. Purification, distribution, intracellular localization and action on proteins. Biochem. J., 1989, vol. 264, pp. 467-473.

21. Zavasnik-Bergant T., Turk B. Cysteine cathepsins in the immune response. Tissue Antigens, 2006, vol. 67, pp. 349-355.

22. Lorand L., Conrad S.M. Transglutaminase. Mol. Cell Biochem., 1984, vol. 58, pp. 9-35.


Login or Create
* Forgot password?