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Taurine:AMysteriousMolecule
withIntriguingPossibili8es
Downloadtheslidesfrom:
h2p://people.csail.mit.edu/seneff/
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Outline1. Introduction2. Some Biochemistry3. Some Observed Benefits of Taurine
The Skin The Heart The Pancreas The Brain The Blood
4. Mitochondrial Diseases5. Encephalitis6. Cancer7. Summary
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1. Introduction
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Haveyouthoughtabouttaurine?*
*AnnLauritzen,WiseTradiFonsWorkshop,WAP011,Dallas,TX
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WhatisTaurine?
Taurineisthemostcommonfreeaminoacidinthebody
Taurineisneverincorporatedintoanyprotein,andithardlyeverparFcipatesinanyreacFon
Yettaurineisfoundinhighconcen-traFonintheheart,brain,andliver
Whatisitdoingthere???
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SomeInteres8ngFactsaboutTaurine*
Importantinmanymarinespeciesforosmosis(asanosmolyte) Shallowwaterclamsandsnailshave
significantlymorethandeeperwaterspecies
Catsbecomeblindifraisedwithouttaurine
Braintaurinelevelsdeclinewithageinmammals;replacedwith
glutamate ArgumentusedtojusFfypresencein
energydrinks
*P.H.Yancey,JExperimentalBiology08,819-830,005.
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TaurinehasManyKnownRoles*
MaintainsosmoFcbalanceincells BileacidformaFon(digestfats) Rolesinmitochondria
HelpsthemmaintaintheirmembranepotenFal Suppressessuperoxidesynthesis(oxidaFondamage)
ClinicalobservaFons Maintainshealthyskin Protectsagainstdiabetesandheartdisease Protectsagainstheartarrhythmias Lowtaurineinbloodassociatedwithmanycancers
*Wesselingetal.,Hypertension.009,53,909-911
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Taurineisfoundonlyinanimal-basedfoods
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FoodSourcesofTaurine
Eggs,meat,fish,seafood,dairy
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FishOil+Taurine*
ExperimentondiabeFc/obesemice,threegroups ishoil ishoil+taurine Soybeanoil
Serumglucoselevelssignificantlylowerinmicefedfishoil(withorwithouttaurine) ishoil+taurinegrouphadenhancedGLUT4
distribuFoninplasmamembraneofmuscle
Fssue. GLUT4isthekeycatalystforglucoseuptakeinmuscles
*Mikamietal.,J.oodSci.01Jun,77(6),H114-0.
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AProvoca8veHypothesis
Taurineisverystable(manyclaimitisinert) Taurineisstoredinheartandbrainasbufferfor
sulfatesupplyduringextremeadversecondiFons EncephaliFsleadstosulfaterenewal!
Hypochlorite(bleach)[releasedbyimmunecellstofightinfecFon]
ever[enhancesenergyofreacFon] Seizures[induceelectriccurrentandprovidefree
electrons]
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TheImportanceofSulfate:SO4-2
Ihavetracedmostmoderndiseasestoadeficiencyinthesupplyofsulfate(Iwilltalk
muchmoreaboutthistomorrow)
TwocriFcalpoints:SulfaFonofcholesterolisessenFalforcholesterol
transportsulfatedeficiencyimpliescholesterol
deficiencySulfaFonisessenFalformanagingsugar:
insufficientsulfatesupplyleadstodiabetes
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2. Some Biochemistry
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Taurine!
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IsTaurineanAminoAcid?
Sulfonyl
Carboxylisreplaced
bySulfonyl
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TaurineSynthesisPathway*
*Wesselingetal.,
Hypertension.009,
53,909-911
PotentanFoxidant
Sourceofsulfate
EssenFalaminoacid
EssenFalto
proteinfolding
Ifyouhaveto
synthesizetaurine
fromprecursors,
theseotherrolesaresacrificed!
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BigHintsfromEarlyLiterature*
ArFclepublishedin1960 edcholesteroltomonkeys
Inducedatherosclerosis Ifsulfur-containingnutrients
areadded,atherosclerosisis
prevented
Taurineworkedaswellasothermoleculeslikecysteine,
methionine,andglutathione
*G.V.Mannetal.,Am.J.Clin.Nutr.8,491-497,1960.
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BreakingdownTaurinetogetSulfate
SuchareacFonmightbepossibleinthehuman,butitsnoteasy
AHint:hypochloriteisreleased
byneutrophilstofightinfecFonCitricAcidCycle
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AnotherUsefulReac8on
CH7NO3S+HONH4+CH3COO-+HS+O
taurine+waterammonia+acetate+hydrogensulfide+oxygen cysteine
N-acetylcysteine
VasorelaxaFon
Oxidizetothiosulfate&cholesterolsulfate
GenerateATP
NutriFonalsupplementfor
Tylenoloverdoseandtotreat
sulfatedeficiencyinauFsm
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3. Some Observed Benefits of Taurine
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TaurocholicAcid:inBileAcids
Makesbileacidsmorewatersoluble
taurine
cholesterol
AidsindigesFngfats
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The Skin
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SLS:aSkinIrritant*
Sodiumlaurylsulfate(SLS)isaddedtoshampoosmainlytomakethemfoamy
Surfactant(=surfaceacFveagent)
UsedinmanycommercialformulaFonsbecauseitisinexpensive,offersgreat
foaming,andcanbethickenedeasilywithsalt SLSisaskinirritant--inducesdry,scalyskindueto
itssurfactanteffects
*LeeandMaibach,ContactDermaFFs,1995,13,1-7
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Taurine,SLS,andtheSkin*
TaurineaccumulatesinoutermostkeraFnocytelayeroftheskinfollowingUVexposure SFmulatessynthesisofceramides,cholesterol,andfa2yacids
SLSinducesanincreaseinwaterlossthroughtheskin,inflammaFon,andproliferaFon
IncubaFonw/SLS+taurine DecreaseinIL-1andprostaglandinE(inflammatoryagents) StabilizaFonofmembraneintegrity ImprovementinkeraFnocyteviability
*B.Anderheggenetal.,JCosmetSci.006Jan-eb;57(1),1-10
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The Heart
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SuddenCardiacDeath*
Suddencardiacdeathistheleadingcauseofdeathinindustriallydevelopedcountries
Accountsfor300,000-500,000deathsperyearinU.S.
DuetoventricularfibrillaFon:life-threateningheartarrhythmia Manifestedbylowheartratevariability
Triggeredbyadrenalininresponsetostress
IntracellularpotassiumandcalciumdysregulaFoninsufficientmembranecholesterol?
*G.E.Billman,AmJPhysiolHeartCircPhysiol97:H1171-H1193,009
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Cardioprotec8veEffectsofTaurine*
TaurineisnormallyfoundinhighestconcentraFonintheheart AnFarrhythmiceffectsobservedexperimentally
incats,dogsandguineapigs.
AddiFonoftaurine Preventslossofpotassiumbymyocardium Reversesadverseeffectsofadrenalinanddigoxin EliminatesthepathologicalECGchangescausedby
strophanthininisolatedguineapighearts.
Myhypothesis:Istaurineasourceofsulfateforcholesterolsulfatesynthesis?
*GeorgyEby,TaurineRoleinCardiologyandCardiacArrhythmias
h2p://george-eby-research.com/html/taurine.html
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HighDietaryTaurineReducesApoptosis
(CellDeath)andAtherosclerosis* Highdietaryfishassociatedwithdecreased
cardiovasculardeathrate
Taurineishighlyconcentratedinfish Highdietarytaurinereducesriskofcoronary
heartdiseaseandinsulinresistance
Taurinedeficiencycanalsoleadtoobesity,ariskfactorforheartdisease
*A.Zullietal.,Hypertension,53,1017-10,009
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HighDietaryTaurineReducesApoptosis
andAtherosclerosis:Experiment*
Rabbitsfedhighcholesteroldiet Examinedeffectoftaurine
supplementsonlemaincoronaryartery
ResultsReducedserumhomocysteinelevelsEndoplasmicReFculumstressreducedin
endothelialcellswhichprotectedthemfromapoptosis
ReducedatherosclerosisinarterywallReducedserumHDL
*A.Zullietal.,Hypertension,53,1017-10,009
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HighDietaryTaurineReducesApoptosis
andAtherosclerosis*:MyInterpreta8on Taurinereactedwithhypochloritewhichalloweditto
bemetabolizedtosulfate
ProtectedLDLfromhypochloritetoxicity ReduceduptakeofLDLintoplaque
PlateletsuFlizednewlyavailablesulfatetoproducecholesterolsulfatefromcholesterolobtainedfromHDL
DepletedHDL
HomocysteinecouldbedivertedtocysteineandglutathioneinsteadofbeingheldinreserveasanalternaFvesourceofsulfate.
Serumhomocysteinelevelsdropped*A.Zullietal.,Hypertension,53,1017-10,009
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Recapitula8on Suddencardiacdeathisleadingcauseofdeathin
WesternnaFons
Taurineishighlyconcentratedintheheart Protectsfromsuddencardiacdeath
Lowdietarytaurineassociatedwithincreaseininsulinresistance,obesity,andheartdisease
Taurineprotectsrabbitsfromcholesterol-diet-inducedcardiovasculardisease
Ihypothesizethattheseeffectsareduetotaurine'sabilitytopromotecholesterolsulfatesynthesis
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The Pancreas
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TaurineandPancrea8cIsletCells*
Motherratsfedlow-proteindietduringgestaFon
andlactaFon
Offspringhadvulnerableisletsintheirpancreas(leadingtodiabetes)
ExcessproducFonoftoxicnitricoxide Increasedapoptosis(celldeath)
Supplementwithtaurineinprotein-deficientmothersalleviatestheseeffects
*KGoosseetal.,JournalofEndocrinology(009)00,177187
Thisshowshow
maternaldiet
canhavelong-
termeffectsonoffspring!
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Taurine,Fructose,andDiabetes*
*Nandhinietal.,SingaporeMedJ,46(),8-87,005
ructoseinducesdiabetesRatsfedcornstarchcompared
withratsfedfructose(60%ofdietarycalories)
ructoseinducedinsulinresistance(well-knownresponse)
Supplementwith%taurinesoluFonadlibitumprotectedratsfrominsulinresistance
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Taurine,Fructose,andDiabetes*
*Nandhinietal.,SingaporeMedJ,46(),8-87,005
CON=cornstarch
RU=fructose
TAU=taurine
TaurineCompletelyEliminatedtheSugarSpikeCausedbyructose
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The Brain
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TaurineinDevelopment*
HighestconcentraFonoccursindevelopingbrain
TaurineconcentraFonsfallduringdevelopment
Convertedtosulfate? Neonateshave3xlevelsofadults Trueforhumans,monkeys,mice,rabbits,rats,
andinsects
*R.J.Huxtable,PhysiologicalReviews7(1),101-163,Jan199
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TaurineisNeuroprotec8ve*
Taurinepreventsexcitotoxicityinducedbyglutamateinneurons
Mitochondrialelectrongradientiscalciumregulated
AcFvaFonbyglutamate Extracellularcalciuminflux MobilizaFonfrominternalstores(mitochondria) Associatedwithdecreaseinmitochondrialenergy
metabolism
Pretreatmentwithtaurinenormalizedcalciumhomeostasisandpreventedmitochondrialimpairment
*A.ElIdrissiandE.Trenkner,J.Neuroscience,19(1),9459-9468,1999.
mitochondrion
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The Blood
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TaurineProtectsPlateletsfromBloodClots*
*K.C.Hayesetal.,Am.J.Clin.Nutr.1989;49:111-6.
Taurineisespeciallyconcentratedinnervoussystemandplatelets Catsareoenafflictedwitha
taurine-deficiencycardiomyopathy
alongwitharterialthromboembolism- Bloodclotblocksflowtoheart
TaurinesuppressesreleaseofthromboxanebyplateletswhichtriggersbloodclotformaFon
- Studyconfirmedthisistrueforhumansaswell
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Sub-op8maltaurinestatusmaypromote
platelethyperaggregabilityinvegetarians*
Plasma taurine levels are lower, andurinary taurine excretion is substantiallylower, in vegetarians than in omnivores.
Platelets are rich in taurine, whichfunctions physiologically to dampen thecalcium influx evoked by aggregatingagonists thereby down-regulating platelet
aggregation.
*M..McCarty,MedicalHypotheses,63(3),46-433,004.
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Outline1. Introduction2. Some Biochemistry3. Some Observed Benefits of Taurine
The Skin The Heart The Pancreas The Brain The Blood
4. Mitochondrial Diseases5. Encephalitis6. Cancer7. Summary
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4. Mitochondrial Diseases
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MitochondrialDiseases*
MitochondriaconvertfoodintoATPforenergy MitochondrialstageIimpairment
associatedwithmanyneurological
andmusculardisorders
MitochondrialDiseases OencausedbymutaFons
inmitochondrialgenes
Symptomsincludepoorgrowth,lossofmusclecoordinaFon,muscleweakness,visualproblems,hearingproblems,learning
disabiliFes,heartdisease,liverdisease,kidneydisease,
gastrointesFnaldisorders,respiratorydisorders,neurological
problems,autonomicdysfuncFon,anddemenFa.
*romWikipedia
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Humanmitochondrialdiseases
causedbylackoftaurinemodifica8oninmitochondrialtRNAs*
*KirinoandSuzuki,RNABiology(),41-44,June005.
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DefectsfromGene8cMitochondrialDisorders*
*KirinoandSuzuki,RNABiology(),41-44,June005.
MutaFonspreventtaurinea2achmentstotRNAs
(1)ImpairUUGgenetranslaFon(taurine)
NADH-CoenzymeQreductaseimpaired MitochondrialComplexIdisrupted
()ImpairAAAandAAG(taurine+S)
DefectinwholemitochondrialtranslaFon QuesFon:DoestheaddiFonalSplayahighlysignificant
roleinenablinggenetranslaFon??
Generictaurinedeficiencymightleadto
similarmitochondrialimpairments
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Fever,Au8sm,andMitochondria*
oundaplausiblelinkbetweenmitochondria,fever,andtaurine
everimpactsauFsmSomeregressaerfever,someimproveSubsetwithmitochondrialdysfuncFonregress
AggressivetreatmentmayworsenoutcomeAcetaminophen(Tylenol)depletessulfateFeversuppressionpreventssulfateregenera4onfromtaurine?
*Shoffneretal.,JChildNeurol.009Sep
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FeverPlusMitochondrialDiseaseCould
BeRiskFactorsforAu8s8cRegression*
*h2p://blog.auFsmspeaks.org/010/03/11/fever-regression/
ChildrenwithASDand
mitochondrialdisease
60%with
regressionevents
70%withfever
orinfecFon
1/3with
vaccinaFon
Allchildrenwith
ASD(1in110
childrenborn)
14%ofthechildrenwith
bothauFsmand
mitochondrialdiseasesufferedregression
followingvaccinaFon
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5. Encephalitis
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AProvoca8veProposal:
Encephali8sisProtec8ve!
Taurineiskeptinreserveasabufferforsulfatesupply
EncephaliFsenablesconversionoftaurinetosulfate
ThisisanimportantposiFveoutcomeofencephaliFs
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WhatisEncephali8s?
EncephaliFsisanacuteinflammaFonofthebrain UsuallycausedbyinfecFon,mostoenbyavirus,but
someFmesbybacteria,afungus,oraparasite.
Symptoms Headache ever Confusion Sleepiness aFgue Seizuresandconvulsions Tremors Memoryproblems
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Figh8ngtheInfec8on:
NitricOxideandHypochlorite Neutrophilsfollowmicrobes
intobrain
A2ackmicrobeswithanFmicrobialagents:
- Nitricoxide- Hypochlorite
ExcessnitricoxideammoniacomplexreacFonintheastrocyte
reesuptaurinetoprotectfromhypochloritedamage
(bybecomingtaurinechloramine)
Neutrophil
Nitric
oxide
hypochlorite
Astrocyte
taurine chloramine
ammoniataurine
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TaurineChloramineisEnergized!
Althoughitisbelievedthattaurineisinert,taurinechloraminecanbemetabolizedto
sulfate!!(atleastbysomespecies)
Canhumansdothis??maybe!
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SomeMoreHelpfromAstrocytes
Astrocytesreleasebothtaurineandglutamateaerswellinginresponsetoammonia
exposure
GlutamateisanacFveneurotransmi2ercapableofinducingaHzresonance
phenomenon
ThiscouldbeakeysourceofseizuresSeizuresprovideelectriccurrent
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GlutamateCycling
Synapse
mitochondrion
Astrocyte
PresynapFcneuron
PostsynapFcneuron
GlutamateisanacFveneurotransmi2er ConversiontoglutaminerendersitinacFve
duringtransport
glutamate
glutamine
Ammonia
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GlutamateduringEncephali8s
Synapse
mitochondrion
ammonia
Astrocyte
PresynapFcneuron
PostsynapFcneuron
DuringencephaliFs,astrocyte
releasesammoniafromglutamineinmitochondria
andshipsoutglutamate
glutamate
glutamine
Ammonia
Glutamatecaninduceseizures
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WhyisAmmoniaNeededinthe
Mitochondrion? Toreplacetaurine! Astrocytereleasesbothtaurineandglutamate
intothemedium
Ammoniareplacestaurineasbufferingagentinmitochondria
HelpsthemmaintainbasicpHTHISREESUPTAURINE
TOPRODUCESULATE!!!
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GlutamateduringEncephali8s
Synapse
mitochondrion
ammonia
Astrocyte
PresynapFcneuron
PostsynapFcneuron
Ammoniareplacestaurinein
mitochondrionandfreesuptaurineforsomethingelse!
glutamate
glutamine
Ammonia
TAURINE!
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Hypochlorite+TaurineSalva8on!
Neutrophil
Nitric
oxide
hypochlorite
Astrocyte
taurine chloramine
ammoniataurine
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ARoleforMicrobes!*
Hypothesis:braininfecFonallowsbacteriatosupplysulfatetothebrain
UnderstresscondiFons,glutamateisreleasedbyastrocytesinthebrainandmetabolizedto-ketoglutarateintheneurons
(subsFtutesforglucosemetabolismtogenerateenergy) EcoliandmanyotherbacteriacanuFlizetheenzyme
-ketoglutaratedioxygenasetometabolizetaurine Inputsoxygen,-ketoglutarate,taurine Outputscarbondioxidesuccinate,sulfiteand
aminoacetaldehyde
ThisenzymeisinducedduringsulfatestarvaFon Sulfiteiseasilyoxidizedtosulfate
Microbesallowedtoflourishinthebraintosupplysulfate! *K.P.McCuskerandJ.P.Klinman*TetrahedronLe2ers50(009)611613
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Recapitula8on
EncephaliFsmaybeamechanismtorenewsulfatesupplytothebrain,bybreakingdown
taurine
Complexmechanisminvolvesglutamate,hypochlorite,nitricoxide,ammonia,etc.
everandseizuresalsoprovidecatalysis Bacteriamaybepermi2edintothebrainto
helpcarryoutthereacFon
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6. Cancer
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ProgressiveinhibiFonofapoptosis(celldeath)andinducFonofangiogenesis(bloodvessel
growth)contributetotumoriniFaFon,growth
andmetastasisinthepathogenesisofbreast
cancer
TaurinedisplaysanFneoplasFceffectsthroughDownregulaFonofangiogenesisEnhancementoftumorcellapoptosis
TaurineandBreastCancer*
*I.M.ElAgouzaetal.Angiogenesis14,31330,011
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TaurineandBreastCancer*
*I.M.ElAgouzaetal.Angiogenesis14,31330,011
85women50withdiagnosedbreastcancer10withbenigntumors5withfamilyhistory0controls
Serumtaurinesharplyreducedinwomenwithbreastcancer(p
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TaurineandBreastCancer*
0
4
6
8
10
1
14
16
control highriskgroup cancerpaFents
VEG/TN
VEG/taurine
69-fold
increase
*I.M.ElAgouzaetal.Angiogenesis14,31330,011
VEG
accelerates
growth
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TaurineInducesApoptosis*
Tumor
cell
Tumor
cell
Tumor
cell
Tumor
cellTN-
VEG
Proliferate
Die
Tumorcellsarerobustagainstexposuretotoxicagents;
theyproliferatewhileothernormalcellsdie
*A.Jacobietal,AnFcancerDru s16 9 ,917-91,005.
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TaurineInducesApoptosis*
Tumor
cell
Tumor
cell
Tumor
cell
Tumor
cellTN-
VEG
Proliferate
Die
Tumorcellsarerobustagainstexposuretotoxicagents;
theyproliferatewhileothernormalcellsdie
*A.Jacobietal,AnFcancerDru s16 9 ,917-91,005.
+Taurine
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LowSerumTaurineandCancer
Manydifferentcancershavebeenfoundtobeassociatedwithunusuallylowserumtaurinelevels
Breastcancer Ovariancancer Bladdercancer Lungcancer Uterinecancer Livercancer Coloncancer Gastro-intesFnalcancer Endometrialcancer
Hypothesis:cancerdepletestaurineby
converFngittosulfate
Tumorcellstypically
overproducesulfated
polysaccharides
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7. Summary
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FoodSourcesofTaurine
Eggs,meat,fish,seafood,dairy
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Summary
TaurineisafascinaFngandpoorlyunderstoodmolecule!
Weneedtoworryaboutdietarydeficiencies,especiallyvegetarians
TaurineisprotecFveincancer,heartdisease,anddiabetesi.e.,themajordiseasesofmodernFmes
TaurineplaysanessenFalroleindevelopment Taurinesmanybenefitsmaystemfromitsrolein
supplyingabufferforsulfatetothebody
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Thank you!
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*igure10inL.-.Huetal,MolPharmacol75:734,009
HydrogenSulfideProtectsMitochondria*
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Taurine-modifiedtRNAsin
Mitochondria*
* S ki t l WIRE RNA 011 376 386