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Taurine 8 pp 153-165 | Cite as

Taurine Deficiency and MELAS Are Closely Related Syndromes

  • Stephen W. SchafferEmail author
  • Chian Ju Jong
  • Danielle Warner
  • Takashi Ito
  • Junichi Azuma
Conference paper
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 776)

Abstract

MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is a mitochondrial disease caused by one or more mutations of tRNALeu(UUR). These mutations reduce both the aminoacylation of tRNALeu(UUR) and a posttranslational modification in the wobble position of tRNALeu(UUR). Both changes result in reduced transcription of mitochondria-encoded proteins; however, reduced aminoacylation affects the decoding of both UUG and UUA while the wobble defect specifically diminishes UUG decoding. Because 12 out of the 13 mitochondria-encoded proteins are more dependent on UUA decoding than UUG decoding, the aminoacylation defect should have a more profound effect on protein synthesis than the wobble defect, which more specifically alters the expression of one mitochondria-encoded protein, ND6. Taurine serves as a substrate in the formation of 5-taurinomethyluridine-tRNALeu(UUR); therefore, taurine deficiency should mimic 5-taurinomethyluridine-tRNALeu(UUR) deficiency. Hence, the wobble hypothesis predicts that the symptoms of MELAS mimic those of taurine deficiency, provided that the dominant defect in MELAS is wobble modification deficiency. On the other hand, if the aminoacylation defect dominates, significant differences should exist between taurine deficiency and MELAS. The present review tests this hypothesis by comparing the symptoms of MELAS and taurine deficiency.

Keywords

Respiratory Chain Activity Taurine Treatment Renal Defect Puromycin Aminonucleoside Taurine Deficiency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviation

MELAS

Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes

References

  1. Anan R, Nakagawa M, Miyata M, Higuchi I, Nakao S, Suehara M, Osame M, Tanaka H (1995) Cardiac involvement in mitochondrial diseases. Circulation 91:955–961PubMedCrossRefGoogle Scholar
  2. Anderson PA, Baker DH, Corbin JE, Helper LC (1979) Biochemical lesions associated with taurine deficiency in the cat. J Anim Sci 49:1227–1234PubMedGoogle Scholar
  3. Arakawa K, Kudo T, Ikawa M, Morikawa N, Kawai Y, Sahashi K, Lee JD, Kuriyama M, Miyamori I, Okazawa H, Yoneda M (2010) Abnormal myocardial energy-production state in mitochondrial cardiomyopathy and acute response to L-arginine infusion. Circ J 74:2702–2711PubMedCrossRefGoogle Scholar
  4. Azuma J, Sawamura A, Awata N, Hasegawa H, Ogura K, Harada H, Ohta H, Yamauchi K, Kishimoto S (1983) Double-blind randomized crossover trial of taurine in congestive heart failure. Curr Therapeut Res 34:543–557Google Scholar
  5. Bagley PJ, Stipanuk MH (1995) Rats fed a low protein diet supplemented with sulfur amino acids have increased cysteine dioxygenase activity and increased taurine production in hepatocytes. J Nutr 125:933–940PubMedGoogle Scholar
  6. Blondel O, Bailbe D, Portha B (1990) Insulin resistance in rats with non-insulin-dependent diabetes induced by neonatal (5 days) streptozotocin: evidence for reversal following phlorizin treatment. Metabolism 39:787–793PubMedCrossRefGoogle Scholar
  7. Chang KJ (2000) Effect of taurine and β-alanine on morphological changes of pancreas in streptozotocin-induced rats. Adv Expt Med Biol 483:571–577CrossRefGoogle Scholar
  8. Chiang LM, Jong YJ, Huang SC, Tsai JL, Pang CY, Lee HC, Wei YH (1995) Heteroplasmic mitochondrial DNA mutation in a patient with mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes. J Formos Med Assoc 94:42–47PubMedGoogle Scholar
  9. Davies WE, Harding NJ, Kay IS, Hopkins PC (1994) The role of taurine in mammalian hearing. Adv Expt Biol Med 359:393–398Google Scholar
  10. Gaull GE (1986) Taurine as a conditionally essential nutrient in man. J Am Coll Nutr 5:121–125PubMedGoogle Scholar
  11. Geggel HS, Ament ME, Heckenlively JR, Martin DA, Koppel JD (1985) Nutritional requirement for taurine in patients receiving long-term parenteral nutrition. N Engl J Med 312:142–146PubMedCrossRefGoogle Scholar
  12. Golubnitschaja O, Moenkemann H, Kim K, Mozaffari MS (2003) DNA damage and expression of checkpoint genes p21(WAF1/CIP1) and 14-3-3 sigma in taurine-deficient cardiomyocytes. Biochem Pharmacol 66:511–517PubMedCrossRefGoogle Scholar
  13. Han X, Chesney RW (2012) The role of taurine in renal disorders. Amino Acids 43:2249–2263Google Scholar
  14. Hansen SH (2001) The role of taurine in diabetes and the development of diabetic complications. Diabetes/Metabol Res Rev 17:330–346CrossRefGoogle Scholar
  15. Harris NG, Plant HD, Inglis BA, Briggs RW, Jones HC (1997) Neurochemical changes in the cerebral cortex of treated and untreated hydrocephalic rat pups quantified with in vitro 1H-NMR spectroscopy. J Neurochem 68:305–312PubMedCrossRefGoogle Scholar
  16. Hayes KC, Carey RE, Schmidt SY (1975) Retinal degeneration associated with taurine deficiency in the cat. Science 188:949–951PubMedCrossRefGoogle Scholar
  17. Hayes KC, Stephan ZF, Sturman JA (1980) Growth depression in taurine-depleted infant monkeys. J Nutr 110:2058–2064PubMedGoogle Scholar
  18. Heller-Stilb B, van Roeyen C, Rascher K, Hartwig HG, Huth A, Seeliger MW, Warskulat U, Haussinger D (2002) Disruption of the taurine transporter gene (taut) leads to retinal degeneration in mice. FASEB J 16:231–233PubMedGoogle Scholar
  19. Hilton G (1995) MELAS: a mitochondrial encephalomyopathy syndrome. J Neurosci Nurs 27:278–282PubMedCrossRefGoogle Scholar
  20. Hirano M, Konishi K, Arata N, Iyori M, Saruta T, Kuramochi S, Akizuki M (2002) Renal complications in a patient with A-to-G mutation of mitochondrial DNA at the 3243 position of leucine tRNA. Int Med 41:113–118CrossRefGoogle Scholar
  21. Hirano M, Pavlakis SG (1994) Mitochondrial myopathy, encephalopathy, lactic acidosis and strokelike episodes (MELAS): current concepts. J Child Neurol 9:4–13PubMedCrossRefGoogle Scholar
  22. Huxtable RJ (1992) Physiological actions of taurine. Physiol Rev 72:101–163PubMedGoogle Scholar
  23. Iizuka T, Sakai F (2005) Pathogenesis of stroke-like episodes in MELAS: Analysis of neurovascular cellular mechanisms. Current Neurovasc Res 2:29–45CrossRefGoogle Scholar
  24. Imaki H, Moretz R, Wisniewski H, Neuringer M, Sturman J (1987) Retinal degeneration in 3-month-old rhesus monkey infants fed a taurine-free human infant formula. J Neurosci Res 18:602–614PubMedCrossRefGoogle Scholar
  25. Ito T, Kimura Y, Uozumi Y, Takai M, Muraoka S, Matsuda T, Ueki K, Yoshiyama M, Ikawa M, Okabe M, Schaffer SW, Fujio Y, Azuma J (2008) Taurine depletion caused by knocking out the taurine transporter gene leads to cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol 44:927–937PubMedCrossRefGoogle Scholar
  26. Jacobsen JG, Smith LH Jr (1968) Biochemistry and physiology of taurine and taurine derivatives. Physiol Rev 48:424–511PubMedGoogle Scholar
  27. Jong CJ, Azuma J, Schaffer S (2012) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42:2223–2232PubMedCrossRefGoogle Scholar
  28. Kirino Y, Yasukawa T, Ohta S, Akira S, Ishihara K, Watanabe K, Suzuki T (2004) Codon-specific translational defect caused by a wobble modification deficiency in mutant tRNA from a human mitochondrial disease. Proc Natl Acad Sci 101:15070–15075PubMedCrossRefGoogle Scholar
  29. Lake N, de Roode M, Nattel S (1987) Effects of taurine depletion on rat cardiac electrophysiology: in vivo and in vitro studies. Life Sci 40:997–1005PubMedCrossRefGoogle Scholar
  30. Lake N, Malik N, De Marte L (1988) Taurine depletion leads to loss of rat optic nerve axons. Vision Res 28:1071–1076PubMedCrossRefGoogle Scholar
  31. Latkany P, Ciulla TA, Cucchillo P, Malkoff MD (1999) Mitochondrial maculopathy: Geographic atrophy of the macula in the MELAS associated A to G 3243 mitochondrial DNA point mutation. Am J Ophthalmol 128:112–114PubMedCrossRefGoogle Scholar
  32. Maassen JA, Hat LM, van Essen E, Heine RJ, Nijpels G, Tafrechi RSJ, Raap AK, Janssen GMC, Lemkes HHPJ (2004) Mitochondrial diabetes: molecular mechanisms and clinical presentation. Diabetes 53(Suppl 1):S103–S109PubMedCrossRefGoogle Scholar
  33. Maassen JA, Hart LM, Janssen GMC, Reiling E, Romijn JA, Lemkes HH (2006) Mitochondrial diabetes and its lessons for common type 2 diabetes. Biochem Soc Trans 34:819–823PubMedCrossRefGoogle Scholar
  34. Mozaffari MS, Patel C, Abdelsayad R, Schaffer SW (2006) Accelerated NaCl-induced hypertension in taurine-deficient rat: role of renal function. Renal Int 70:329–337Google Scholar
  35. Mozaffari MS, Tan BH, Lucia MA, Schaffer SW (1986) Effect of drug-induced taurine depletion on cardiac contractility and metabolism. Biochem Pharmacol 35:985–989PubMedCrossRefGoogle Scholar
  36. Novotny MJ, Hogan PM, Flannigan G (1994) Echocardiographic evidence for myocardial failure induced by taurine deficiency in domestic cats. Can J Vet Res 58:6–12PubMedGoogle Scholar
  37. Novotny MJ, Hogan PM, Paley DM, Adams HR (1991) Systolic and diastolic dysfunction of the left ventricle induced by taurine deficiency in cats. Am J Physiol 261:H121–H127PubMedGoogle Scholar
  38. Oermann E, Warskulat U, Heller-Stilb B, Haussinger D, Zilles K (2005) Taurine-transporter gene knockout-induced changes in GABAA, kainite and AMPA but not NMDA receptor binding in mouse brain. Anat Embryol 210:363–372PubMedCrossRefGoogle Scholar
  39. Pasantes-Morales H, Arzate ME, Quesada O, Huxtable RJ (1987) Higher susceptibility of taurine-deficient rats to seizures induced by 4-aminopyridine. Neuropharmacology 26:1721–1725PubMedCrossRefGoogle Scholar
  40. Pion PD, Kittleson MD, Thomas WP, Skiles ML, Rogers QR (1992) Clinical findings in cats with dilated cardiomyopathy and relationship of findings to taurine deficiency. J Am Vet Med Assoc 201:267–274PubMedGoogle Scholar
  41. Pion PD, Kittleson MD, Rogers QR, Morris JG (1987) Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy. Science 237:764–748PubMedCrossRefGoogle Scholar
  42. Roysommuti S, Suwanich A, Lerdweeraphon W, Thaeomor A, Jirakulsomchok D, Wyss JM (2009) Sex dependent effects of perinatal taurine exposure on the arterial pressure control in adult offspring. Adv Exp Med Biol 643:135–144PubMedCrossRefGoogle Scholar
  43. Rummelt V, Folberg R, Ionasescu V, Yi H, Moore KC (1993) Ocular pathology of MELAS syndrome with mitochondrial DNA nucleotide 3243 point mutation. Ophthalmology 100:1757–1766PubMedGoogle Scholar
  44. Schaffer SW, Wilson GL (1993) Insulin resistance and mechanical dysfunction in hearts of Wistar rats with streptozotocin-induced non-insulin-dependent diabetes mellitus. Diabetologia 36:195–199PubMedCrossRefGoogle Scholar
  45. Schmidt SY, Berson EL, Watson G, Huang C (1977) Retinal degeation in cats fed casein III. Taurine deficiency and ERG amplitudes. Invest Ophthalmol Visual Sci 16:673–678Google Scholar
  46. Sergeeva OA, Fleischer W, Chepkova AN, Warskulat U, Haussinger D, Siebler M, Hess HL (2007) GABAA–receptor modification in taurine transporter knockout mice causes striatal disinhibition. J Physiol 585:539–548PubMedCrossRefGoogle Scholar
  47. Silbert L, Durocher A, Biller J (1996) The “S” in MELAS. J Stroke Cerebrovasc Dis 6:67–71PubMedCrossRefGoogle Scholar
  48. Smith PR, Bain SC, Good PA, Hattersley AT, Barnett AH, Gibson JM, Dodson PM (1999) Pigmentary retinal dystrophy and the syndrome of maternally inherited diabetes and deafness caused by the mitochondrial DNA 3243 tRNALeu A to G mutation. Ophthalmology 106:1101–1108PubMedCrossRefGoogle Scholar
  49. Sproule DM, Kaufmann P (2008) Mitochondrial encephalopathy, lactic acidosis and strokelike episodes: Basic concepts, clinical phenotype, and therapeutic management of MELAS syndrome. Ann N Y Acad Sci 1142:133–158PubMedCrossRefGoogle Scholar
  50. Sproule DM, Kaufmann P, Engelstad K, Starc TJ, Hordof AJ, DeVivo DC (2007) Wolff-Parkinson-White syndrome in patients with MELAS. Arch Neurol 64:1625–1627PubMedCrossRefGoogle Scholar
  51. Sue CM, Crimmins DS, Soo YS, Pamphlett R, Presgrave CM, Kotsimbos N, Jean-Francois MJB, Byrne E, Morris JGL (1998) Neuroradiological features of six kindreds with MELAS tRNALeu A3243G point mutation: implications for pathogenesis. J Neurl Neurosug Psychiatry 65:233–240CrossRefGoogle Scholar
  52. Thambisetty M, Newman NJ, Glass JD, Frankel MR (2002) A practical approach to the diagnosis and management of MELAS: case report and review. Neurologist 8:302–312PubMedCrossRefGoogle Scholar
  53. Trachtman H, Barbour R, Sturman JA, Finberg L (1988) Taurine and osmoregulation: Taurine is a cerebral osmoprotective molecular in chronic hypernatremic dehydration. Pediatr Res 23:35–39PubMedCrossRefGoogle Scholar
  54. Trachtman H, Del Pizzo R, Futterweit S, Levine D, Rao PS, Valderrama E, Sturman JA (1992) Taurine attenuates renal disease in chronic puromycin aminonucleoside nephropathy. Am J Physiol 262:F117–F123PubMedGoogle Scholar
  55. Turnbull HE, Lax NZ, Diodato D, Ansorge O, Turnbull DM (2010) The mitochondrial brain: From mitochondrial genome to neurodegeneration. Biochim Biophys Acta 1802:111–121PubMedCrossRefGoogle Scholar
  56. Tyson JE, Lasky R, Flood D, Mize C, Picone T, Paule CL (1989) Randomized trial of taurine supplementation for infants  <  1,300-gram birth weight: effect on auditory brainstem-evoked responses. Pediatrics 83:406–415PubMedGoogle Scholar
  57. Vallecalle-Sandoval MH, Heaney G, Sersen E, Sturman JA (1991) Comparison of the developmental changes of the brainstem auditory evoked response (BAER) in taurine-supplemented and taurine-deficient kittens. Int J Dev Neurosci 9:571–579PubMedCrossRefGoogle Scholar
  58. Van den Ouweland JMW, Lemkes HHPJ, Ruitenbeek W, Sandkuijl LA, de Vijlder MF, Struyvenberg PAA, van de Kamp JJP, Maaseen JA (1992) Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat Genet 1:368–371PubMedCrossRefGoogle Scholar
  59. Vinton NE, Heckenlively JR, Laidlaw SA, Martin DA, Foxman SR, Ament ME, Kopple JD (1990) Visual function in patients undergoing long-term total parenteral nutrition. Am J Clin Nutr 52:895–902PubMedGoogle Scholar
  60. Vionnet N, Passa P, Froguel P (1993) Prevalence of mitochondrial gene mutations in families with diabetes mellitus. Lancet 342:1429–1430PubMedCrossRefGoogle Scholar
  61. Warskulat U, Borsch E, Reinehr R, Heller-Stilb B, Monnighoff I, BuchczykD DM, Flogel U, Kappert G, Soboll S, Beer S, Pfeffer K, Marschall HU, Gabrielsen M, Amiry-Moghaddam M, Ottersen OP, Dienes HP, Haussinger D (2006) Chronic liver disease is triggered by taurine transporter knockout in the mouse. FASEB J 20:574–576PubMedGoogle Scholar
  62. Warskulat U, Flogel U, Jacoby C, Harwig HG, Thewissen M, Merx MW, Molojavyi A, Heller-Stilb B, Schrader J, Haussinger D (2004) Taurine transporter knockout depletes muscle taurine levels and results in severe skeletal muscle impairment but leaves cardiac function uncompromised. FASEB J 18:577–579PubMedGoogle Scholar
  63. Weiss C, Glowatzki E, Fuchs P (2009) The postsynaptic function of type II cochlear afferents. Nature 461:1126–1129CrossRefGoogle Scholar
  64. Wen GY, Sturman JA, Wisniewski HM, Lidsky AA, Cornwell AC, Hayes KC (1979) Tapetum disorganization in taurine-depleted cats. Invst Opthalmol Visual Sci 18:1200–1206Google Scholar
  65. Yasukawa T, Suzuki T, Suzuki T, Ueda T, Ohta S, Watanabe K (2000) Modification defect at anticodon wobble nucleotide of mitochondrial tRNAsLeu(UUR) with pathogenic mutations of mitochondrila myopathy, encephalopathy, lactic acidosis, and stroke-like episodes. J Biol Chem 275:4251–4257PubMedCrossRefGoogle Scholar
  66. Yatabe Y, Miyakawa S, Miyazaki T, Matsuzaki Y, Ochiai N (2003) Effects of taurine administration in rat skeletal muscles on exercise. J Orthop Sci 8:415–419PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Stephen W. Schaffer
    • 1
    Email author
  • Chian Ju Jong
    • 1
  • Danielle Warner
    • 1
  • Takashi Ito
    • 2
  • Junichi Azuma
    • 2
  1. 1.Department of PharmacologySchool of Medicine, University of South AlabamaMobileUSA
  2. 2.Hyogo University of Health Sciences, School of PharmacyKobeJapan

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