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Does Taurine Prolong Lifespan by Improving Heart Function?

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Taurine 9

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 803))

Abstract

Taurine transporter knockout (TauTKO) mice die prematurely, an effect attributed to premature aging. However, taurine deficiency also causes severe pathology, including the development of a cardiomyopathy that can be fatal. The present review discusses one of the major mechanisms underlying the development of the cardiomyopathy. The cascade begins with taurine deficiency-mediated impairment of electron transport chain function, which mediates the initial decline in contractile function. The heart then begins the process of ventricular and biochemical remodeling, which worsens the severity of the contractile defect. A key defect that develops during ventricular remodeling is impaired sarcoplasmic reticular (SR) Ca2+ handling, which arises from a series of steps that include elevated protein phosphatase 1 activity, diminished Ca2+-calmodulin-dependent protein kinase II (CaMKII) activity, reduced levels of phosphorylated phospholamban and finally impaired SR Ca2+ ATPase activity. Also contributing to ventricular remodeling is the loss of cardiomyocytes via apoptosis.

Taurine deficiency also promotes premature aging, a complex phenomenon mediated in part by telomere shortening, elevations in mitochondrial ROS generation, mitochondrial DNA damage and inflammation. The initial insult driving premature aging in taurine deficient hearts is enhanced mitochondrial ROS generation, which in turn activates key signaling kinases that increase NF-κB content, leading to enhanced production of pro-inflammatory mediators. Chronic inflammation arises from both the production of pro-inflammatory mediators and the decline in taurine chloramine production, the latter which inhibits the inflammatory process. Finally, inflammation is a recognized mediator of premature aging.

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References

  • Back SH, Scheunder D, Han J, Song B, Ribick M, Wang J, Gildersleeve RD, Pennathur S, Kaufman RJ (2009) Translation attenuation through eIF2α phosphorylation prevents oxidative stress and maintains the differentiated state in β cells. Cell Metab 10:13–26

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Beeri R, Chaput M, Guerrero JL, Kawase Y, Yosefy C, Abedat S, Karakikes I, Morel C, Tisosky A, Sullivan S, Handschumacher MD, Gilon D, Vlahakes GJ, Hajjar RJ, Levine RA (2010) Gene delivery of sarcoplasmic reticulum calcium ATPase inhibits ventricular remodeling in ischemic mitral regurgitation. Circ Heart Fail 3:627–634

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Belanger MC, Ouellet M, Queney G, Moreau M (2005) Taurine deficient dilated cardiomyopathy in a family of golden retrievers. J Am Anim Hosp Assoc 41:284–291

    Article  PubMed  Google Scholar 

  • Bodnar AG, Ouellette M, Frolkis M, Holt SE, Chiu CP, Morin GB, Harley CB, Shay JW, Lichtsteiner S et al (1998) Extension of life-span by introduction of telomerase into normal human cells. Science 279:349–352

    Article  CAS  PubMed  Google Scholar 

  • Brown MK, Naidoo N (2012) The endoplasmic reticulum stress response in aging and age-related diseass. Frontiers Physiol 3:1–10

    Google Scholar 

  • Carnes BA (2011) What is lifespan regulation and why does it exist? Biogerontology 12:367–374

    Article  PubMed  Google Scholar 

  • Chung HY, Cesari M, Anton S, Marzetti E, Giovannini S, Seo AY, Carter C, Yu BP, Leeuwenburg C (2009) Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res Rev 8:18–30

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Delic D, Warskulat U, Borsch E, Al-Qahtani S, Al-Quraishi S, Haussinger D, Wunderlich F (2010) Loss of ability to self-heal malaria upon taurine transporter deletion. Infect Immun 78:1642–1649

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Erickson JR (2014) Mechanisms of CaMKII activation in the heart. Front Pharmacol 5:59

    Article  PubMed Central  PubMed  Google Scholar 

  • Erickson JR, Pereira L, Wang L, Han G, Ferguson A, Dao K, Copeland RJ, Despa F, Hart GW, Ripplinger CM, Bers DM (2013) Diabetic hyperglycaemia activates CaMKII and arrhythmias by O-linked glycosylation. Nature 502:372–376

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Fox PR, Sturman JA (1992) Myocardial taurine concentrations in cats with cardiac disease and in healthy cats fed taurine modified diets. Am J Vet Res 53:237–241

    CAS  PubMed  Google Scholar 

  • Gaull GE (1986) Taurine as a conditionally essential nutrient in man. J Am Coll Nutr 5:121–125

    Article  CAS  PubMed  Google Scholar 

  • Gaertner TR, Kolodziej SJ, Wang D, Kobayashi R, Koomen JM, Stoops JK (2004) Comparative analyses of the three dimensional structures and enzymatic properties of α, β, γ and δ isoforms of Ca2 + -calmodulin-dependent protein kinase II. J Biol Chem 279:12484–12494

    Article  CAS  PubMed  Google Scholar 

  • Hahn WC, Stewart SA, Brooks MW, York SG, Eaton E, Kurachi A, Beijersbergen RL, Knoll JH, Meyerson M, Weinberg RA (1999) Inhibition of telomerase limits the growth of human cancer cells. Nat Med 5:1164–1170

    Article  CAS  PubMed  Google Scholar 

  • Harding HP, Novoa I, Zhang Y, Zeng H, Wek R, Schapira M, Ron D (2000) Regulated translation initiation controls stress-induced gene expression in mammalian cells. Mol Cell 6:1099–1108

    Article  CAS  PubMed  Google Scholar 

  • Harley CB, Futcher AB, Greider CW (1990) Telomeres shorten during ageing of human fibroblasts. Nature 345:458–460

    Article  CAS  PubMed  Google Scholar 

  • Harman D (1983) Free radical theory of aging: consequences of mitochondrial aging. Age 6:86–94

    Article  CAS  Google Scholar 

  • Hayes KC, Carey RE (1975) Retinal degeneration associated with taurine deficiency in the cat. Science 188:949–951

    Article  CAS  PubMed  Google Scholar 

  • Hayflick L, Moorhead PS (1961) The serial cultivation of human diploid cell strains. Exp Cell Res 25:585–621

    Article  CAS  PubMed  Google Scholar 

  • Helenius M, Hannine M, Lehtinen SK, Salminen A (1996) Aging-induced upregulation of nuclear binding activities of oxidative stress responsive NF-κB transcription factor in mouse cardiac muscle. J Mol Cell Cardiol 28:487–498

    Article  CAS  PubMed  Google Scholar 

  • 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 16:231–233

    CAS  PubMed  Google Scholar 

  • Herbener GH (1976) A morphometric study of age-dependent changes in mitochondrial population of mouse liver and heart. J Gerontol 31:8–12

    Article  CAS  PubMed  Google Scholar 

  • Hiona A, Leeuwenburgh C (2008) The role of mitochondrial DNA mutations in aging and sarcopenia: implications for the mitochondrial vicious cycle theory of aging. Exp Gerontol 43:24–33

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Hoelz A, Narin AC, Kuriyan J (2003) Crystal structure of a tetradecameric assembly of the association domain of Ca2+/calmodulin-dependent kinase II. Mol Cell 11:1241–1251

    Article  CAS  PubMed  Google Scholar 

  • Hussain SG, Ramaiah KVA (2007) Reduced eIF2α phosphorylation and increased proapoptotic proteins in aging. Biochem Biophys Res Commun 355:365–370

    Article  CAS  PubMed  Google Scholar 

  • Huxtable RJ, Lippincott SE (1982) Relative contribution of diet and biosynthesis to the taurine content of the adult rat. Drug Nutr Interact 1:153–168

    CAS  PubMed  Google Scholar 

  • Ishii T, Miyazawa M, Hartman PS, Ishii N (2011) Mitochondrial superoxide anion (O2 -) inducible “mev-1” animal models for aging research. BMB Rep 44:298–305

    Article  CAS  PubMed  Google Scholar 

  • 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 a cardiomyopathy with cardiac atrophy. J Mol Cell Cardiol 44:927–937

    Article  CAS  PubMed  Google Scholar 

  • Ito T, Schaffer S, Azuma J (2014) The effect of taurine on chronic heart failure: actions of taurine against catecholamines and angiotensin II. Amino Acids 46:111–119

    Article  CAS  PubMed  Google Scholar 

  • Jager R, Bertrand MJM, Gorman AD, Vandenabeele P, Samali A (2012) The unfolded protein response at the crossroads of cellular life and death during endoplasmic reticulum stress. Biol Cell 104:259–270

    Article  CAS  PubMed  Google Scholar 

  • Jong CJ, Azuma J, Schaffer S (2012) Mechanism underlying the antioxidant activity of taurine: prevention of mitochondrial oxidant production. Amino Acids 42:2223–2232

    Article  CAS  PubMed  Google Scholar 

  • Kanayama A, Inoue J, Sugita-Konishi Y, Shimizu M, Miyamoto Y (2002) Oxidation of IκBα at methionine 45 is one cause of taurine chloramines-induced inhibition of NF-κB activation. J Biol Chem 277:24049–24056

    Article  CAS  PubMed  Google Scholar 

  • Karlseder J, Broccoli D, Dai Y, Hardy S, deLang T (1999) p53- and ATM-dependent apoptosis induced by telomeres lacking TRF2. Science 283:1321–1325

    Article  CAS  PubMed  Google Scholar 

  • Kirkwood TBL, Austad SN (2000) Why do we age? Nature 408:233–238

    Article  CAS  PubMed  Google Scholar 

  • Kittleson MD, Keene B, Pion PD, Loyer CG (1997) Results of the multicenter spaniel trial (MUST): taurine- and carnitine-responsive dilated cardiomyopathy in American cocker spaniels with decreased plasma taurine concentration. J Vet Intern Med 11:204–211

    Article  CAS  PubMed  Google Scholar 

  • Knopf K, Sturman JA, Armstrong M, Hayes KC (1978) Taurine: an essential nutrient for the cat. J Nutr 108:773–778

    CAS  PubMed  Google Scholar 

  • Kocsis JJ, Kostos VJ, Baskin SI (1976) Taurine levels in the heart tissues of various species. In: Huxtable R, Barbeau A (eds) Taurine. Raven, New York, pp 145–153

    Google Scholar 

  • Kolesar JE, Safdar A, Abadi A, MacNeil LG, Crane JD, Tarnopolsky MA, Kaufman BA (2014) Defects in mitochondrial DNA replication and oxidative damage in muscle of mtDNA mutator mice. Free Radic Biol Med 75:241–251

    Article  CAS  PubMed  Google Scholar 

  • Kontny E, Szczepanska K, Kowalczewski J, Kurowska M, Janicka I, Marcinkiewcz J, Maslinski W (2000) The mechanism of taurine chloramine inhibition of cytokine (interleukin-6, interleukin-8) production by rheumatoid fibroblast-like synoviocytes. Arthritis Rheum 43:2169–2177

    Article  CAS  PubMed  Google Scholar 

  • Kurata S, Ohtsuki T, Wada T, Kirino Y, Takai K, Watanabe K, Ramakrishnan V, Suzuki T (2008) Modified uridines with C5-methylene substituents at the first position of the tRNA anticodon stabilizes U-G wobble pairing during decoding. J Biol Chem 283:18801–18811

    Article  CAS  PubMed  Google Scholar 

  • Lombardini JB (1991) Taurine: retinal function. Brain Res Rev 16:151–169

    Article  CAS  PubMed  Google Scholar 

  • Ma YS, Wu SB, Lee WY, Cheng JS, Wei YH (2009) Response to the increase of oxidative stress and mutation of mitochondrial DNA in aging. Biochem Biophys Acta 1790:1021–1029

    Article  CAS  PubMed  Google Scholar 

  • MacLennan DH, Kranias EG (2003) Phospholamban: a crucial regulator of cardiac contractility. Nat Rev 4:566–577

    Article  CAS  Google Scholar 

  • Malhotra JD, Kaufman RJ (2007) Endoplasmic reticulum stress and oxidative stress: a vicious cycle or a double-edged sword? Antioxid Redox Signal 9:2277–2293

    Article  CAS  PubMed  Google Scholar 

  • Marcinkiewicz J, Grabowska A, Bereta J, Bryniarski K, Nowak B (1998) Taurine chloramines down-regulates the generation of murine neutrophil inflammatory mediators. Immunopharmacology 40:27–38

    Article  CAS  PubMed  Google Scholar 

  • Martin GM, Austad SN, Johnson TE (1996) Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat Genet 13:25–34

    Article  CAS  PubMed  Google Scholar 

  • Meyer T, Hanson PI, Stryer L, Schulman H (1992) Calmodulin trapping by calcium-calmodulin-dependent protein kinase. Science 256:1199–1202

    Article  CAS  PubMed  Google Scholar 

  • Minamino T, Kitakaze M (2010) ER stress in cardiovascular disease. J Mol Cell Cardiol 48:1105–1110

    Article  CAS  PubMed  Google Scholar 

  • Mozaffari MS, Tan BH, Lucia MA, Schaffer SW (1986) Effect of drug-induced taurine depletion on cardiac contractility and metabolism. Biochem Pharmacol 35:985–989

    Article  CAS  PubMed  Google Scholar 

  • Muller FL, Lustgarten MS, Jang Y, Richardson A, Van Remmen H (2007) Trends in oxidative aging theories. Free Radic Biol Med 43:477–503

    Article  CAS  PubMed  Google Scholar 

  • Novotny MJ, Hogan PM, Paley DM, Adams HR (1991) Systolic and diastolic dysfunction of the left ventricle induced by dietary taurine deficiency in cats. Am J Physiol 261:H121–H127

    CAS  PubMed  Google Scholar 

  • Olovnikov AM (1996) Telomeres, telomerase and aging: origin of the theory. Exp Gerontol 31:443–448

    Article  CAS  PubMed  Google Scholar 

  • Pion PD, Kittleson MD, Rogers QR, Morris JG (1987) Myocardial failure in cats associated with low plasma taurine: a reversible cardiomyopathy. Science 237:764–768

    Article  CAS  PubMed  Google Scholar 

  • 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 201:267–274

    CAS  PubMed  Google Scholar 

  • Ramila KC, Jong CJ, Pastukh V, Ito T, Azuma J, Schaffer SW (2015) Role of protein phosphorylation in excitation-contraction coupling in taurine deficient hearts. Am J Physiol. In press

    Google Scholar 

  • Rascher K, Servos G, Berthold G, Harwig HG, Warskulat U, Heller-Stilb B, Haussinger D (2004) Light deprivation slows but does not prevent the loss of photoreceptors in taurine transporter knockout mice. Vision Res 44:2091–2100

    Article  CAS  PubMed  Google Scholar 

  • Rattan SI (2006) Theories of biological aging: genes, proteins and free radicals. Free Rad Res 40:1230–1238

    Article  CAS  Google Scholar 

  • Rosenberg OS, Deindl S, Sung RJ, Narin AC, Kuriyan J (2005) Structure of the autoinhibited kinase domain of CaMKII and SAXS analysis of the holoenzyme. Cell 123:849–860

    Article  CAS  PubMed  Google Scholar 

  • Schmidt SY, Berson EL, Watson G, Huang C (1977) Retinal degeneration in cats fed casein. III. Taurine deficiency and ERG amplitudes. Invest Ophthalmol Visual Sci 16:673–678

    CAS  Google Scholar 

  • Schuller-Levis G, Mehta PD, Rudelli R, Sturman J (1990) Immunologic consequences of taurine deficiency in cats. J Leukocyte Biol 47:321–331

    CAS  PubMed  Google Scholar 

  • Schuller-Levis GB, Park E (2003) Taurine: new implications for an old amino acid. FEMS Microbiol Lett 226:195–202

    Article  CAS  PubMed  Google Scholar 

  • Stockl P, Zanckl C, Hutter E et al (2007) Partial uncoupling of oxidative phosphorylation induces premature senescence in human fibroblasts and yeast mother cells. Free Radic Biol Med 43:947–958

    Article  PubMed  Google Scholar 

  • Sturman JA (1986) Nutritional taurine and central nervous system development. Ann NY Acad Sci 477:196–213

    Article  CAS  PubMed  Google Scholar 

  • Trifunovic A, Hansson A, Wredenberg A, Rovio AT, Dufour E, Khvorostov I, Spelbrink JN, Wibom R, Jacobs HT, Larsson NG (2005) Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production. Proc Natl Acad Sci U S A 102:17993–17998

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Varki A, Cummings RD, Esko JD (2009) In: Varki A, Cummings RD, Esko JD, Freeze HH, Stanley P, Bertozzi CR, Hart GW, Etzler ME (eds) Essentials of glycobiology. 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, Chapter 26

    Google Scholar 

  • Vijg J, Campisi J (2008) Puzzles, promises and a cure for aging. Nature 454:1065–1071

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Von Zglinicki T (2002) Oxidative stress shortens telomeres. Trends Biochem Sci 27:339–344

    Article  Google Scholar 

  • Wang CH, Wu SB, Wu YT, Wei YH (2013) Oxidative stress response elicited by mitochondrial dysfunction: implication in the pathophysiology of aging. Expt Biol Med 238:450–460

    Article  Google Scholar 

  • Yamamoto Y, Yamamoto H (2015) Enzymatic and non-enzymatic post-translational modifications linking diabetes and heart disease. J Diabetes Invest 6:16–17

    Google Scholar 

  • Zandi E, Rothwarf DM, Delhase M, Hayakawa M, Karin M (1997) The IkappaB kinase complex (IKK) contains two kinase subunits, IKKalpha and IKKbeta, necessary for IkappaB phosphorylation and NF-kappaB activation. Cell 91:243–252

    Article  CAS  PubMed  Google Scholar 

  • Zanfir A, Readnower R, Long BW, McCracken J, Aird A, Alvarez A, Cummins TD, Li Q, Bhatnager BG, Prabhu A, Bolli R, Jones SP (2012) Protein-O-GlcNAcylation is a novel cytoprotective signal in cardiac stem cells. Stem Cells 31:765–775

    Article  Google Scholar 

  • Zeidan Q, Hart GW (2010) The intersections between O-GlcNAcylation and phosphorylation: implications for multiple signal pathways. J Cell Sci 123:13–22

    Article  CAS  PubMed Central  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Pharmacology, College of Medicine, University of South Alabama, Mobile, AL, USA

    Stephen W. Schaffer, K. C. Ramila, Chian Ju Jong, Aza Shetewy, Kayoko Shimada & Eugene Cioffi

  2. Hyogo University of Health Sciences, School of Pharmacy, Kobe, Japan

    Takashi Ito & Junichi Azuma

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  1. Stephen W. Schaffer
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  2. K. C. Ramila
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  3. Chian Ju Jong
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  4. Aza Shetewy
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  6. Takashi Ito
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  7. Junichi Azuma
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  8. Eugene Cioffi
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Correspondence to Stephen W. Schaffer .

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Editors and Affiliations

  1. Chair of Immunology, Medical College Jagiellonian University, Krakow, Poland

    Janusz Marcinkiewicz

  2. Department of Pharmacology, College of Medicine University of South Alabama, Mobile, Alabama, USA

    Stephen W. Schaffer

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Schaffer, S.W. et al. (2015). Does Taurine Prolong Lifespan by Improving Heart Function?. In: Marcinkiewicz, J., Schaffer, S. (eds) Taurine 9. Advances in Experimental Medicine and Biology, vol 803. Springer, Cham. https://doi.org/10.1007/978-3-319-15126-7_45

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