Sulfite and base for the treatment of familial amyloidotic polyneuropathy: two additive approaches to stabilize the conformation of human amyloidogenic transthyretin
Tóm tắt
Recently, we presented evidence that sulfite protects transthyretin (TTR) from normal human individuals and heterozygotes with amyloidogenic TTR mutations against the decay of tetramers into monomers. In this paper we demonstrate a stabilizing effect of sulfite on TTR tetramers from a familial amyloidotic polyneuropathy (FAP) patient homozygous for the most-common amyloidogenic TTR-V30 M mutation. We compare the conformational stability of partially sulfonated TTR from a heterozygote for normal TTR and amyloidogenic TTR-V30 M with the stability of untreated TTR from a compound heterozygote for amyloidogenic TTR-V30 M and TTR-T119 M known to have only minor or no problems of FAP. Using a combination of polyacrylamide gel electrophoresis (PAGE) and sodium dodecyl sulfate (SDS) gradient PAGE we demonstrate that TTR dimers containing amyloidogenic TTR mutations decay into monomers at pH<7.4. Increasing the pH by some 0.2 units within physiological ranges, i.e., pH 7.0–7.4, and sulfonation of TTR were observed to have additive inhibitory effects on the transition of dimers into monomers. We conclude that mild acidifying episodes in the interstitial volume of tissues at risk for amyloidosis could contribute to the development of FAP. Early and permanent efforts to counteract acidosis by treatment with base could possibly help to delay the onset of the disease. The intake of sulfite could support these efforts.
Tài liệu tham khảo
Benson MD (1995) Amyloidosis. In: Sciver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic basis of inherited diseases, vol 3. McGraw-Hill, New York, pp 4139–4191
Holmgren G, Steen L, Ekstedt J, Groth C-G, Ericzon B-G, Eriksson S, Anderson O, Karlberg I, Norden G, Nakazato M, Hawkins P, Richardson S, Pepys M (1991) Biochemical effect of liver transplantation in two Swedish patients with familial amyloidotic polyneuropathy (FAP-met30). Clin Genet 40:242–246
Holmgren G, Costa PMP, Andersson C, Asplund K, Steen L, Beckman L, Nylander P–O, Teixeira A, Saraiva MJM, Costa PP (1994) Geographic distribution of TTR met30 carriers in northern Sweden: discrepancy between carrier frequency and prevalence rate. J Med Genet 31:351–354
Sousa A, Andersson R, Drugge U, Holmgren G, Sandgren O (1993) Familial amyloidotic polyneuropathy in Sweden: geographic distribution, age of onset, and prevalence. Hum Hered 43:288–294
Holmgren G, Ando Y, Wikström L, Rydh A, Suhr O (1997) Discordant symptoms in monozygotic twins with familial amyloidotic polyneuropathy (FAP) (TTR met30). Amyloid 4:178–180
Munar–Ques M, Pedrosa JL, Coelho T, Gusmao L, Seruca R, Amorim A, Sequeiros J (1999) Two pairs of proven monozygotic twins discordant for familial amyloid neuropathy (FAP) TTR Met30. J Med Genet 36:629–623
Ando Y, Ohtsu Y, Terazaki H, Kibayashi K, Nakamura M, Ando E, Matsunaga N, Obayashi K, Uchoino M, Ando M, Tsunenari S (2000) Japanese monozygotic twins with familial amyloidotic polyneuropathy (FAP) (amyloidogenic TTR Val30Met). Amyloid 7:133–136
Altland K, Benson MD, Ferlini A, Husby G, Linke RP, Salvi F, Saraiva, MJM, Skinner M, Sletten K, Steinmetz A, Winter P (1996) Most cases of familial amyloidotic polyneuropathy (FAP) are associated with amino acid substitutions destabilizing the folded state of transthyretin monomers. Neuromusc Disord 6:S17
Miroy GJ, Lai Z, Lashuel H, Peterson SA, Strang C, Kelly JW (1996) Inhibiting transthyretin amyloid fibril formation via protein stabilization. Proc Natl Acad Sci U S A 93:15051–15056
Peterson SA, Klabunde T, Lashuel HA, Purkey H, Sacchiettini JC, Kelly JW (1998) Inhibiting transthyretin conformational changes that lead to amyloid fibril formation. Proc Natl Acad Sci U S A 95:12956–12960
Altland K, Winter P, Sauerborn MK (1999) Electrically neutral microheterogeneity of human plasma transthyretin (prealbumin) detected by isoelectric focusing in urea gradients. Electrophoresis 20:1349–1364
Altland K, Winter P (1999) Potential treatment of transthyretin-type amyloidoses by sulfite. Neurogenetics 2:183–188
Alves IL, Hays MT, Saraiva MJM (1993) Comparative stability and clearance of [Met30] transthyretin and [Met119] transthyretin. Eur J Biochem 249:662–668
Coelho T, Choão R, Sousa A, Alves I, Torres MF, Saraiva MJM (1996) Compound heterozygotes of transthyretin Met30 and transthyretin Met119 are protected from the devastating effects of familial amyloidotic polyneuropathy. Neuromusc Disord 6 [Suppl 1]:S20
Alves IL, Altland K, Almeida MR, Winter P, Saraiva MJM (1997) Screening and biochemical characterization of transthyretin variants in the Portuguese population. Hum Mutat 9:226–233
Altland K, Winter P (2003) Polyacrylamide gel electrophoresis followed by sodium dodecyl sulfate gradient polyacrylamide gel electrophoresis for the study of the dimer to monomer transition of human transthyretin. Electrophoresis 14:2265–2271
Street D, Bangsbo J, Juel C (2001) Interstitial pH in human muscle during and after dynamic graded exercise. J Physiol 537:993–998
Frassetto L, Morris Jr RC, Sellmeyer DE, Todd K, Sebastian A (2001) Diet, evolution and aging. The pathological effects of the post-agricultural inversion of the potassium-to-sodium and base-to chloride ratios in the human diet. Eur J Nutr 40:200–213
Wardener HE, MacGregor GA (2002) Harmful effects of dietary salt in addition to hypertension. J Hum Hypertens 16:213–223
Remer T, Manz F (1995) Potential renal acid load of foods and its influence on urine pH. J Am Diet Assoc 95:791–797
Leaf A, Xiao Y-F (2001) The modulation of ionic currents in excitable tissues by n-3 polyunsaturated fatty acids. J Membr Biol 184:263–271
Eaton SB, Konnor M (1985) Paleolithic nutrition. A consideration of its nature and current implications. N Engl J Med 312:283–289
Sebastian A, Frassetto LA, Sellmeyer DE, Merriam RL, Morris Jr RC (2002) Estimation of the net acid load of the diet of ancestral preagricultural Homo sapiens and their hominid ancestors. Am J Clin Nutr 76:1308–1316
Simopoulos AP (2001) n–3 Fatty acids and human health: defining strategies for public policy. Lipids 36:S84–S89
Kishikawa M, Nakanishi T, Miyazaki A, Shimizu A (1999) Enhanced amyloidogenicity of sulfonated transthyretin in vitro, a hypothetical etiology of senile amyloidosis. Amyloid 6:183–186
Zhang Q, Kelly W (2003) Cys10 mixed disulfides make transthyretin more amyloidogenic under mildly acidic conditions. Biochemistry 42:8756–8761
Hötzel D, Muskat E, Bitsch I, Aign W, Althoff D-J, Cremer H-D (1969) Thiaminmangel und Unbedenklichkeit von Sulfit für den Menschen. Intern Z Vit Forschung 39:372–383