Abstract
There are several evidences, suggesting a relationship between hyperhomocysteinemia and various diseases of the visual system. Therefore in this study the effects of homocysteinylation on aggregation and fibrillation of lens crystallins were studied using spectroscopic techniques, SDS-PAGE and western blot analysis. The results of UV–Vis absorption studies suggest an induction of lens protein aggregation after homocysteinylation. Furthermore, the existence of fibril in the aggregate of lens proteins confirmed by Congo red absorption measurement and Thioflavin-T fluorescence assay. Taken together the results of SDS-PAGE and Western blotting, it is suggested that almost all detectable eye lens crystallins are prone to aggregation by homocysteinylation, while α-Crystallin comprises the main portion of lens protein aggregate. Overall this study may suggest lens protein homocysteinylation as a possible mechanism to explain the relationship between hyperhomocysteinimia and some impairments of the visual system.
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Abbreviations
- ANS:
-
1-Anilino-8-naphthalene sulfonate
- CR:
-
Congo red
- HCTL:
-
Homocysteine thiolactone
- Hcy:
-
Homocysteine
- ThT:
-
Thioflavin-T
- TSP:
-
Total soluble proteins
- SDS-PAGE:
-
Sodium dodecyl sulfate poly acrylamide gel electrophoresis
References
Abu El-Asrar AM, Abdel Gader AGM, Al-Amro SA, Al-Attas OS (2002) Eur J Ophthalmol 12(6):495–500
Alfthan G, Aro A, Gey KF (1997) Lancet 349(9049):397
Bełtowski J (2005) Postepy Hig Med Dosw (Online) 59:392–404
Bhaskar H, Chaudhary R (2010) Case Report Med. doi:10.1155/2010/691563
Chiti F, Dobson CM (2006) Annu Rev Biochem 75:333–366
Cho NH, Lim S, Jang HC, Park HK, Metzger BE (2005) Diabetes Care 28(11):2750–2755
Chua B, Kifley A, Wong TY, Mitchell P (2005) Am J Ophthalmol 139(1):181–182
De Falco M, Pollio F, Scaramellino M, Pontillo M, Lieto AD (2000) Clin Exp Obstet Gynecol 27(3–4):188–190
de Jong WW, Hendriks W, Mulders JW, Bloemendal H (1989) Trends Biochem Sci 14(9):365–368
de Jong WW, Terwindt EC, Bloemendal H (1975) FEBS Lett 58(1):310–313
Deminice R, Vannucchi H, Simões-Ambrosio LM, Jordao AA (2011) Eur J Appl Physiol 111(11):2663–2670
Domagała TB, Łacinski M, Trzeciak WH, Mackness B, Mackness MI, Jakubowski H (2006) Cell Mol Biol (Noisy-le-grand) 52(5):4–10
Donaldson P, Kistler J, Mathias RT (2001) News Physiol Sci 16:118–123
Dubin RA, Ally AH, Chung S, Piatigorsky J (1990) Genomics 7(4):594–601
Ganapathy PS, Moister B, Roon P, Mysona BA, Duplantier J, Dun Y, Moister TK, Farley MJ, Prasad PD, Liu K, Smith SB (2009) Invest Ophthalmol Vis Sci 50(9):4460–4470
Hawe A, Sutter M, Jiskoot W (2008) Pharm Res 25(7):1487–1499
Herrmann W, Obeid R (2011) Clin Chem Lab Med 49(3):435–441
Hop CECA, Bakhtiar R (2002) Rapid Commun Mass Spectrom 16(11):1049–1053
Hussein WI, Green R, Jacobsen DW, Faiman C (1999) Ann Intern Med 131(5):348–351
Jakubowski H (1990) Proc Natl Acad Sci USA 87(12):4504–4508
Jakubowski H (1991) EMBO J 10(3):593–598
Jakubowski H (1997) J Biol Chem 272(3):1935–1942
Jakubowski H (1999) FASEB J 13(15):2277–2283
Jakubowski H (2000) J Nutr 130(2S Suppl):377S–381S
Jakubowski H (2006) J Nutr 136(6):1741S–1749S
Kamei A, Hamaguchi T, Matsuura N, Masuda K (2001) Biol Pharm Bull 24(1):96–99
Khalili-Hezarjaribi H, Yousefi R, Moosavi-Movahedi AA (2012) Protein Pept Lett 19(4):450–457
Klunk WE, Jacob RF, Mason RP (1999) Meth Enzymol 309:285–305
Kulshrestha OP, Kulshrestha SN, Khuteta KP, Shukla Y (1983) Indian J Ophthalmol 31(3):267–269
Kumar MS, Koteiche HA, Claxton DP, Mchaourab HS (2009) FEBS Lett 583(1):175–179
Kumar PA, Kumar MS, Reddy GB (2007) Biochem J 408(Pt 2):251–258
Lapko VN, Smith DL, Smith JB (2003) Protein Sci 12(8):1762–1774
Liang JN, Hershorin LL, Chylack LT Jr (1986) Diabetologia 29(4):225–228
Lubsen NH, Aarts HJ, Schoenmakers JG (1988) Prog Biophys Mol Biol 51(1):47–76
MacCoss MJ, McDonald WH, Saraf A, Sadygov R, Clark JM, Tasto JJ, Gould KL, Wolters D, Washburn M, Weiss A, Clark JI, Yates JR 3rd (2002) Proc Natl Acad Sci USA 99(12):7900–7905
Mackness MI, Walker CH, Carlson LA (1987) Clin Chem 33(4):587–588
Mansoor MA, Bergmark C, Svardal AM, Lønning PE, Ueland PM (1995) Arterioscler Thromb Vasc Biol 15(2):232–240
Meehan S, Berry Y, Luisi B, Dobson CM, Carver JA, MacPhee CE (2004) J Biol Chem 279(5):3413–3419
Morgan SL, Baggott JE, Lee JY, Alarcón GS (1998) J Rheumatol 25(3):441–446
Muchowski PJ, Wacker JL (2005) Nat Rev Neurosci 6(1):11–22
Nygård O, Refsum H, Ueland PM, Vollset SE (1998) Am J Clin Nutr 67(2):263–270
Paoli P, Sbrana F, Tiribilli B, Caselli A, Pantera B, Cirri P, De Donatis A, Formigli L, Nosi D, Manao G, Camici G, Ramponi G (2010) J Mol Biol 400(4):889–907
Persa C, Osmotherly K, Chao-Wei Chen K, Moon S, Lou MF (2006) Exp Eye Res 83(4):817–823
Raju I, Abraham EC (2011) PLoS ONE 6(11):e28085
Refsum H (2001) Br J Nutr 85(Suppl 2):S109–S113
Riddles PW, Blakeley RL, Zerner B (1983) Meth Enzymol 91:49–60
Rimm EB, Willett WC, Hu FB, Sampson L, Colditz GA, Manson JE, Hennekens C, Stampfer MJ (1998) JAMA 279(5):359–364
Roedl JB, Bleich S, Reulbach U, Rejdak R, Kornhuber J, Kruse FE, Schlötzer-Schrehardt U, Jünemann AG (2007) J Glaucoma 16(2):234–239
Roedl JB, Bleich S, Reulbach U, Rejdak R, Naumann GOH, Kruse FE, Schlötzer-Schrehardt U, Kornhuber J, Jünemann AGM (2007) J Neural Trans 114(5):571–575
Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) JAMA 270(22):2693–2698
Seshadri N, Robinson K (1999) Curr Cardiol Rep 1(2):91–98
Sikora M, Twardowski T, Jakubowski H (2006) Postepy Biochem 52(4):417–423
Srinivas P, Narahari A, Petrash JM, Swamy MJ, Reddy GB (2010) IUBMB Life 62(9):693–702
Takemoto L, Sorensen CM (2008) Exp Eye Res 87(6):496–501
Thampi P, Hassan A, Smith JB, Abraham EC (2002) Invest Ophthalmol Vis Sci 43(10):3265–3272
Van Montfort R, Slingsby C, Vierling E (2001) Adv Protein Chem 59:105–156
Weger M, Stanger O, Deutschmann H, Temmel W, Renner W, Schmut O, Semmelrock J, Haas A (2002) Graefes Arch Clin Exp Ophthalmol 240(4):286–290
Wistow GJ, Piatigorsky J (1988) Annu Rev Biochem 57:479–504
Wolfe LS, Calabrese MF, Nath A, Blaho DV, Miranker AD, Xiong Y (2010) Proc Natl Acad Sci USA 107(39):16863–16868
Yu NT, DeNagel DC, Pruett PL, Kuck JF Jr (1985) Proc Natl Acad Sci USA 82(23):7965–7968
Acknowledgments
We would like to thank the financial supports of Iran National Science Foundation (INSF)/Grant number: 88001578. Also the financial supports of the research council of Shiraz University are gratefully acknowledged.
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Khazaei, S., Yousefi, R. & Alavian-Mehr, MM. Aggregation and Fibrillation of Eye Lens Crystallins by Homocysteinylation; Implication in the Eye Pathological Disorders. Protein J 31, 717–727 (2012). https://doi.org/10.1007/s10930-012-9451-4
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DOI: https://doi.org/10.1007/s10930-012-9451-4