Yıl: 2022 Cilt: 50 Sayı: 1 Sayfa Aralığı: 37 - 43 Metin Dili: İngilizce DOI: 10.15671/hjbc.669854 İndeks Tarihi: 29-07-2022

CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS

Öz:
Improper folding of the mutant proteins may finally cause several conformational diseases such as Nephrogenic Diabetes Insipidus (NDI). In recent years, as a therapeutic strategy, chaperone treatment for such diseases is among current issues. In our study, we aimed to analyze the effect of several chemical chaperones on mutant V2 receptors which cause NDI. V2R mutant constructs were introduced into the pLV2R. Mutants were transiently expressed in COS-7 cells. After MTT analyses, cell surface ELISA experiment was performed for understanding the rescue potential of the chaperones of the mutated proteins. As a result, we analyzed that rescue potential of a chemical chaperone depends on both chemical compound and the mutation type. We may conclude that such chaperone treatment studies are valuable for development of the therapeutic strategies.
Anahtar Kelime: NDI Chaperone AVPR2

Kimyasal Şaperonların Arjinin Vazopressin Reseptör 2 Mutantları Üzerine Etkisi

Öz:
Mutant proteinlerin yanlış katlanması, Nefrojenik Diabetes İnsipidus gibi bazı konformasyonel hastalıklara sebep olabilmektedir. Son yıllarda, terapötik bir strateji olarak, şaperon tedavisi bu tür hastalıklar için güncel konular arasındadır. Bu çalışmanın amacı, bazı kimyasal şaperonların Nefrojenik Diabetes İnsipidus’a neden olan V2 reseptör mutantları üzerine etkisinin araştırılmasıdır. V2R mutant örnekleri pLV2R vektöründe oluşturulmuştur. Mutant örnekler geçici trasfeksiyon ile COS-7 hücrelerinde ifade edilmiştir. MTT analizinden sonra, mutant proteinler üzerinde şaperonların kurtarma potansiyellerinin analizi için hücre yüzey ve sandviç ELİZA deneyleri uygulanmıştır. Sonuç olarak, kimyasal şaperonların kurtarma potansiyellerinin hem kullanılan kimyasal bileşiğe hem de mutasyonun tipine göre etki ettiği gözlenmiştir. Bu ve bunun gibi şaperon uygulamalarının terapötik stratejilerin geliştirilmesi açısından değerli olduğu sonucuna varılmıştır.
Anahtar Kelime:

Belge Türü: Makale Makale Türü: Araştırma Makalesi Erişim Türü: Erişime Açık
  • 1. J.H. Robben, N.V. Knoers, and P.M. Deen, Cell biological aspects of the vasopressin type-2 receptor and aquaporin 2 water channel in nephrogenic diabetes insipidus, Am. J. Physiol. Renal. Physiol., 291 (2006) F257-70.
  • 2. N. Gregersen, P. Bross, S. Vang, and J.H. Christensen, Protein misfolding and human disease, Annu. Rev. Genomics Hum. Genet., 7 (2006) 103-24.
  • 3. V. Bernier, M. Lagace, D.G. Bichet, and M. Bouvier, Pharmacological chaperones: potential treatment for conformational diseases, Trends Endocrinol. Metab., 15 (2004) 222-228.
  • 4. E. Saglar, F. Deniz, B. Erdem, T. Karaduman, A. Yonem, E. Cagiltay, and H. Mergen, A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family, Endocrine, 46 (2014) 148-53.
  • 5. Daniel G. Bichet, Chapter 2 V2R Mutations and Nephrogenic Diabetes Insipidus. 2009. p. 15-29.
  • 6. C.H. Chen, Chen, W.Y., Liu, H.L., Liu, T.T., Tsou, A.P., Lin, C.Y., Chao, T., Qi, Y., Hsiao, K.J., Identification of mutations in the arginine vasopressin receptor 2 gene causing nephrogenic diabetes insipidus in Chinese patients, J. Hum. Genet., 47 (2002) 66-73.
  • 7. D. Saglar Duzenli, E. Deniz, F. Azal O.B. Erdem, H. Mergen, Mutations in the AVPR2, AVP-NPII, and AQP2 genes in Turkish patients with diabetes insipidus, Endocrine, (2012).
  • 8. B. Erdem, A. Schulz, E. Saglar, F. Deniz, T. Schoneberg, and H. Mergen, Functional characterization of AVPR2 mutants found in Turkish patients with nephrogenic diabetes insipidus, Endocr. Connect., 7 (2018) 56-64.
  • 9. P. Csermely E. Papp, Chemical chaperones: mechanisms of action and potential use., Handb. Exp. Pharmacol., 172 (2006) 405-16.
  • 10. J.H. Robben and P.M. Deen, Pharmacological chaperones in nephrogenic diabetes insipidus: possibilities for clinical application, BioDrugs, 21 (2007) 157-66.
  • 11. J.D. Albright, Reich, M.F., Delos Santos, E.G. Dusza, J.P. Sum F.W. Venkatesan, A.M. Coupet, J. Chan, P.S. Ru,, Mazandarani H, Bailey T., 5-Fluoro-2-methyl-N-[4-(5H-pyrrolo[2,1-c]-[1, 4]benzodiazepin-10(11H)-ylcarbonyl)-3-chlorophenyl] benzamide (VPA-985): an orally active arginine vasopressin antagonist with selectivity for V2 receptors., J. Med. Chem., 41 (1998) 2442-2444.
  • 12. B. Mouillac and C. Mendre, Pharmacological chaperones as potential therapeutic strategies for misfolded mutant vasopressin receptors, Handb Exp Pharmacol, 245 (2018) 63-83.
  • 13. S. Diamant, N. Eliahu, D. Rosenthal, and P. Goloubinoff, Chemical chaperones regulate molecular chaperones in vitro and in cells under combined salt and heat stresses, J. Biol. Chem., 276 (2001) 39586-39591.
  • 14. D.S. Yang, C.M. Yip, T.H. Huang, A. Chakrabartty, and P.E. Fraser, Manipulating the amyloid-beta aggregation pathway with chemical chaperones, J. Biol. Chem., 274 (1999) 32970- 32974.
  • 15. J.H. Robben, M. Sze, N.A.M. Knoers, and P.M.T. Deen, Rescue of vasopressin V2 receptor mutants by chemical chaperones: Specificity and mechanism, Molecul. Biol. Cell, 17 (2006) 379-386.
  • 16. S. Sato, Ward, C.L., Krouse, M.E., Wine, J.J., and Kopito, R. R., Glycerol reverses the misfolding phenotype of the most common cystic fibrosis mutation, J. Biol. Chem., 271 (1996) 635-638.
  • 17. Z. Bebok, C.J. Venglarik, Z. Panczel, T. Jilling, K.L. Kirk, and E.J. Sorscher, Activation of DeltaF508 CFTR in an epithelial monolayer, Am. J. Physiol., 275 (1998) C599-607.
  • 18. Y.X. Tao and P.M. Conn, Chaperoning G protein-coupled receptors: from cell biology to therapeutics, Endocr. Rev., 35 (2014) 602-647.
  • 19. H.I. Cheong, H.Y. Cho, H.W. Park, I.S. Ha, and Y. Choi, Molecular genetic study of congenital nephrogenic diabetes insipidus and rescue of mutant vasopressin V2 receptor by chemical chaperones, Nephrology (Carlton), 12 (2007) 113- 117.
  • 20. B.K. Tamarappoo, B. Yang, and A.S. Verkman, Misfolding of mutant aquaporin-2 water channels in nephrogenic diabetes insipidus, J. Biol. Chem., 274 (1999) 34825-34831.
  • 21. T. Arakawa, D. Ejima, Y. Kita, and K. Tsumoto, Small molecule pharmacological chaperones: From thermodynamic stabilization to pharmaceutical drugs, Biochim. Biophys. Acta, 1764 (2006) 1677-1687.
  • 22. M.A. Brostrom, C.O. Brostrom, Calcium dynamics and endoplasmic reticular function in the regulation of protein synthesis: implications for cell growth and adaptability, Cell Calcium, 34 (2003) 345-363.
  • 23. S.K. Nigam, A.L. Goldberg, S. Ho, M.F. Rohde, K.T. Bush, S. M. Yu, A set of endoplasmic reticulum proteins possessing properties of molecular chaperones includes Ca(2+)-binding proteins and members of the thioredoxin superfamily, J. Biol. Chem., 269 (1994) 1744-1749.
  • 24. S.E. Trombetta, A.J. Parodi, Purification to apparent homogeneity and partial characterization of rat liver UDPglucose:glycoprotein glucosyltransferase, J. Biol. Chem., 267 (1992) 9236-9240.
  • 25. M.E. Egan, M. Pearson, S.A. Weiner, V. Rajendran, D. Rubin, J. Glöckner-Pagel, S. Canny, K. Du, G.L. Lukacs, M.J. Caplan, Curcumin, a major constituent of turmeric, corrects cystic fibrosis defects, Science, 304 (2004) 600-602.
  • 26. B. Erdem Tıncdemir, H. Mergen, E. Saglar Ozer, Evaulation of pharmacochaperone-mediated rescue of mutant V2 receptor proteins, Europ. J. Pharmacol., 865 (2019) 172803.
APA Erdem Tuncdemir B, Karaduman T, Ozcan Turkmen M, Şahin D, MERGEN H, SAGLAR OZER E (2022). CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. , 37 - 43. 10.15671/hjbc.669854
Chicago Erdem Tuncdemir Beril,Karaduman Tugce,Ozcan Turkmen Merve,Şahin Dilara,MERGEN HATICE,SAGLAR OZER EMEL CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. (2022): 37 - 43. 10.15671/hjbc.669854
MLA Erdem Tuncdemir Beril,Karaduman Tugce,Ozcan Turkmen Merve,Şahin Dilara,MERGEN HATICE,SAGLAR OZER EMEL CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. , 2022, ss.37 - 43. 10.15671/hjbc.669854
AMA Erdem Tuncdemir B,Karaduman T,Ozcan Turkmen M,Şahin D,MERGEN H,SAGLAR OZER E CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. . 2022; 37 - 43. 10.15671/hjbc.669854
Vancouver Erdem Tuncdemir B,Karaduman T,Ozcan Turkmen M,Şahin D,MERGEN H,SAGLAR OZER E CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. . 2022; 37 - 43. 10.15671/hjbc.669854
IEEE Erdem Tuncdemir B,Karaduman T,Ozcan Turkmen M,Şahin D,MERGEN H,SAGLAR OZER E "CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS." , ss.37 - 43, 2022. 10.15671/hjbc.669854
ISNAD Erdem Tuncdemir, Beril vd. "CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS". (2022), 37-43. https://doi.org/10.15671/hjbc.669854
APA Erdem Tuncdemir B, Karaduman T, Ozcan Turkmen M, Şahin D, MERGEN H, SAGLAR OZER E (2022). CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. Hacettepe Journal of Biology and Chemistry, 50(1), 37 - 43. 10.15671/hjbc.669854
Chicago Erdem Tuncdemir Beril,Karaduman Tugce,Ozcan Turkmen Merve,Şahin Dilara,MERGEN HATICE,SAGLAR OZER EMEL CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. Hacettepe Journal of Biology and Chemistry 50, no.1 (2022): 37 - 43. 10.15671/hjbc.669854
MLA Erdem Tuncdemir Beril,Karaduman Tugce,Ozcan Turkmen Merve,Şahin Dilara,MERGEN HATICE,SAGLAR OZER EMEL CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. Hacettepe Journal of Biology and Chemistry, vol.50, no.1, 2022, ss.37 - 43. 10.15671/hjbc.669854
AMA Erdem Tuncdemir B,Karaduman T,Ozcan Turkmen M,Şahin D,MERGEN H,SAGLAR OZER E CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. Hacettepe Journal of Biology and Chemistry. 2022; 50(1): 37 - 43. 10.15671/hjbc.669854
Vancouver Erdem Tuncdemir B,Karaduman T,Ozcan Turkmen M,Şahin D,MERGEN H,SAGLAR OZER E CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS. Hacettepe Journal of Biology and Chemistry. 2022; 50(1): 37 - 43. 10.15671/hjbc.669854
IEEE Erdem Tuncdemir B,Karaduman T,Ozcan Turkmen M,Şahin D,MERGEN H,SAGLAR OZER E "CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS." Hacettepe Journal of Biology and Chemistry, 50, ss.37 - 43, 2022. 10.15671/hjbc.669854
ISNAD Erdem Tuncdemir, Beril vd. "CHEMICAL CHAPERONE EFFECTS ON ARGININE-VASOPRESSIN RECEPTOR 2 MUTANTS". Hacettepe Journal of Biology and Chemistry 50/1 (2022), 37-43. https://doi.org/10.15671/hjbc.669854