Methylene blue ichienzaniswa nenzira dzeNAD+: mashandiro, humbowo, uye zvinotaurwa nezvekuzvisanganisa

Methylene blue nezviwedzerwa zvinotengeswa sezvinokwidziridza NAD+ zvose zvinotsanangurwa pachishandiswa mashoko ekuti mitochondria nesimba remasero. Hapana patsananguro mbiri idzi inokuudza kuti chigadzirwa chinoitei chaizvo.

Nzira mbiri idzi dzinoshanda pazvinhu zvakasiyana zvinoyerwa. Imwe inoedza kushandura huwandu hweNAD+ huri mumasero ako. Imwe inoshandura reshiyo pakati pezvimiro zvayo zviviri. Idzi hadzisi nzira mbiri dzinoenda kunzvimbo imwe chete.

Nhamba mbiri dzinogara dzichivhiringidzwa

NAD+ icoenzyme. Inogamuchira maerekitironi maviri, ari muchimiro cheioni yehydride, yobva yava NADH. NADH painopa maerekitironi iwayo kune chimwe chinhu, inova NAD+ zvakare. Masero anoshandisa kutenderera uku nguva dzose: ndiko kunoita kuti simba rinobudiswa muchikafu risvike kumapuroteni anogadzira ATP.

Sezvo NAD+ neNADH zviri zvimiro zviviri zvemorekuru rimwe chete, sero rine zvinhu zviviri zvakasiyana zvakakosha kuyera. Chekutanga ihuwandu hwazvo hwose: kuti NAD+ neNADH zviripo zvakawanda sei pamwe chete. Chechipiri ireshiyo pakati pazvo, inotsanangura kuti zvinotakura maerekitironi zvakatakura zvakawanda sei panguva iyoyo.

Dhamu rinoita kuti musiyano uyu unzwisisike. Huwandu hwemvura iri mudhamu ndihwo huwandu hwose. Kupatsanurwa pakati pemvura yakachengetwa neiri kubudiswa ichiyerera ichienda mberi ndiyo reshiyo. Unogona kukwidziridza reshiyo iyoyo pasina kuwedzera litre, nokuvhura gedhi. Iyi haisi fananidzo yezvinoitwa nemethylene blue. Iri pedyo netsananguro yezvainoita chaizvo.

Nzira yekuwedzera zvinovaka NAD+

Zviwedzerwa zvezvinotangira NAD+, zvinosanganisira nicotinamide riboside, nicotinamide mononucleotide, nenicotinamide, zvinhu zvekuvaka nazvo. Masero anogadzira NAD+ nenzira yekushandisazve zvinhu inonzi salvage pathway, uye zvinotangira izvi zvinopinda munzira iyoyo. Chinangwa ndechekuwedzera huwandu hwose.

Mumhuka, izvi zvakanyatsosimbiswa: mumhando dzakawanda dzinoshandiswa muongororo, NAD+ iri mumatishu inoderera nekukwegura uye nezvirwere zvemetabolism, uye kupa zvinotangira zvayo kunowanzoikwidziridza. Muvanhu, zvinoratidzwa nehumbowo zvishoma. Ongororo dzevanhu dzinoratidza kuti zvinhu izvi zvinokwidziridza mwero weNAD+ unoyerwa muropa. Zvavasati varatidza kuvandudzika kunowirirana pamugumisiro wekiriniki, kureva zvinhu zvingacherechedzwa nemunhu kana izvo ongororo yakarongerwa kuyera.

“Mwero weNAD+ wakawedzera” zvinoyera chimwe chinhu chiri mukati memuviri. Hazvisi zvakawanikwa pamusoro pekuti munhu ainzwa sei, aifamba sei, kana kuti aipora sei.

Zvinoitwa nemethylene blue panzvimbo pezvo

Methylene blue haisi chinhu chinotangira NAD+. Idhayi rinoshanda mukuchinjana kwemaerekitironi, kana kuti redox, rakashandiswa mukurapa kwemakore anopfuura zana, uye mashandisirwo aro akabvumidzwa mashoma kupfuura ari kuongororwa.

Mukati mesero, maenzayimu anovimba neflavin anoiridyusa kusvika pachimiro chisina ruvara, leucomethylene blue, chinozoitwa oxidation zvakare. Maerekitironi angadai akapfuura nemucomplex I, nzvimbo yekutanga yemuketani wekufema kwesero, anogona panzvimbo pezvo kubudiswa muNADH kuburikidza nemethylene blue. NADH inova NAD+.

Reshiyo inokwira. Huwandu hwose hahuwedzeri.

Ongororo yemakonzo pamusoro pemwoyo une chirwere cheshuga yakayera izvi zvakananga mumitochondria yakabviswa mumwoyo. Kuwedzera methylene blue pamwero kubva pa6 kusvika pa18 micromolar panguva yeoxidation yemafuta-asidhi kwakakonzera kuderera kweNADH nereshiyo yeNADH-to-NAD+ zvichienderana nehuwandu hwakawedzerwa. Huwandu chaihwo hweNAD+ hwakachinja zvishoma zvikuru kupfuura hweNADH, sezvaungatarisira pachinhu chinoshandura chimwe chimiro kuita chimwe pane kugadzira zvimwe zvezvimwe zvacho.

Kunoenda maerekitironi iwayo kwakakosha. Mumitochondria yakabviswa muuropi, methylene blue pamwero we100 nanomolar kusvika pa1 micromolar yakavandudza kugadzirwa kwesimba apo muketani wekufema kwesero wakanga wakadziviswa, uye panguva imwe chete yakawedzera kugadzirwa kwehydrogen peroxide ichideredza kubviswa kwayo, mumamiriro ose akaedzwa. Vanyori vanoti hydrogen peroxide yakabva pakuridyuswa kweoxygen zvakananga nemethylene blue yakanga yaridyuswa. Maerekitironi anobuda muNADH nenzira iyi haangonyangarike. Anoenda kuoxygen.

Imwe ongororo yakasiyana mutishu yetendon yeAchilles inotaura izvi zvakajeka. Methylene blue yakadzorera kuenzana kweNAD+/NADH uye yakakwidziridza kugadzirwa kweATP mumasero etendon akakuvara uye mumakonzo akashandiswa kuongorora chirwere chetendon, uye chinyorwa chacho chinoratidza kuti huwandu hwose hweNAD hahuna kuchinja zvine kukosha kwehuwandu.

Zvinoratidzwa neongororo dzematishu nedzemhuka

Ongororo ina mumakumi mana emakore dzinotevera pfungwa imwe chete uye dzinoramba dzichiratidza muganhu wayo.

Mumakonzo aipiwa doro kwenguva refu, ethanol yakaderedza reshiyo dzeNAD+/NADH dzose dziri mucytosol nemumitochondria yechiropa. Kuwedzera methylene blue muchikafu kwakadzivirira shanduko iyoyo zvikuru. Hakuna kuderedza mafuta aiungana muchiropa aikonzerwa neethanol. Kugadzirisa reshiyo hakuna kugadzirisa mugumisiro wacho. Mugumisiro uyu wa1985 unofanirwa kuyeukwa kusati kwaitwa chero chirevo chekuti shanduko yeredox ndiyo inokonzera rubatsiro.

Mumasero echiropa nembeva dzaidya chikafu chine mafuta akawanda, methylene blue yakakwidziridza reshiyo yeNAD+/NADH, yakawedzera SIRT1, yakaderedza kubatanidzwa kwemapoka eacetyl kuPGC-1alpha, yakaita kuti AMPK ishande, uye yakaderedza kuungana kwemafuta muchiropa. Pano mugumisiro wakachinja pamwe chete nereshiyo. Chinyorwa chimwe chetecho chinoratidza kuti shanduko yacho haingorambi ichienda kudivi rimwe chete: three milligrams per kilogram per day yakawedzera huwandu hweDNA yemitochondria zviri nani kupfuura ten, asi kushandiswa kweoxygen nekutumirwa kwezviratidzo neAMPK zvakakwira nehuwandu hwaipiwa.

Mumwoyo une chirwere cheshuga, methylene blue yaipiwa mumvura yekunwa kwemavhiki gumi nerimwe yakaderedza reshiyo yeNADH-to-NAD+ mumitochondria yemwoyo uye yakakwidziridza kushanda kwesirtuin 3. Kubatanidzwa kwemapoka eacetyl kulysine kwakaderera panzvimbo 83 pamapuroteni 34, zvikuru pamapuroteni ekutakura mafuta-asidhi nekuita oxidation yawo. Chikamu cheropa chinobudiswa nemwoyo pakurova kumwe chakavandudzika. Asi kufema kwesero kunotsigirwa necomplex I hakuna kugadziriswa. Uye ongororo yakadzima kushanda kwejini yakapatsanura zvinhu zviviri zviri nyore kuvhiringidza: shanduko yereshiyo yakaitika zvikuru pasina sirtuin 3, asi kubviswa kwemapoka eacetyl kwaivimba nayo.

Muongororo yetendon, methylene blue yakaiswa apo complex I yakanga yavharwa nekemikari inonzi rotenone. Yakaramba ichidzorera kuenzana kweNAD+, uye yakaramba ichitadza kudzivirira kushushikana kunokonzerwa neoxidation, kuparara kwezvinhu zvinotsigira masero, uye kurasikirwa nekukwanisa kwemasero kuramba ari mapenyu. Kudzorera reshiyo kwakanga kusina kukwana kuti tishu ipore.

Pepa rinodhindika rine zvinyorwa zvose zvakashandiswa rinoshandisa mitsara yakafanana.

Nei masirtuin achibatanidzwa munharo idzi

Masirtuin anobvisa mapoka eacetyl pamapuroteni, uye anoshandisa NAD+ kuita izvi. Kushanda kwawo kunochinja zvichienderana nekuwanikwa kweNAD+, saka chero chinhu chinoshandura kuwanikwa kwayo chinozochinja kushanda kwemasirtuin.

Apa ndipo pakavakirwa kushambadza kwakawanda kwe“methylene blue yeNAD+”. Ndipowo panotadza kufamba zvakanaka kufunga kwacho. Kushandura reshiyo kunogona kukwidziridza kushanda kwemasirtuin. Hazvirevi kuti chigadzirwa chinopa NAD+, uye hazvirevi kuti shanduko yacho yakafanana nekutora chinotangira NAD+. Kududzira zviyero izvi maererano neredox kune misungo yakwo yakakodzera kuverengwa usati wagamuchira imwe yetsananguro idzi.

Zvakaedzwa muvanhu

Methylene blue yashandiswa mukiriniki kwemakumi emakore mumamiriro anoda kurapwa nokukurumidza uye kuongororwa: methemoglobinemia, kukuvadzwa kwetsinga kunoenderana neifosfamide, uye kuderera kwakanyanya kweBP panguva yekuvhiyiwa. Aya mashandisirwo ane miganhu uye anoitwa achitarisirwa, kwete humbowo hwekuitora nemuromo zuva nezuva sechinobatsira mashandiro emuviri.

Kutsvaga kwakaitwa kuchinyorwa chino hakuna kuwana ongororo yevanhu yakayera zvinhu zvinobva mukushandurwa kweNAD+ mushure memethylene blue muvazvipiri vane utano. Zvakawanikwa zviri pamusoro zvinobva mumitochondria yakaparadzaniswa, masero akarimwa murabhoritari, tishu yemakonzo, uye zvidimbu zvematishu zvakabviswa muvanhu. Tendon yakabviswa ikachengetwa iri mhenyu mundiro idanho rinobatsira riri pamusoro pekushandisa masero anorimwa murabhoritari. Asi haisati iri munhu.

Zvinyorwa zveongororo dzezvinotangira NAD+ ndezvevanhu zvechokwadi, uye migumisiro yazvo midiki. NAD+ yemuropa inokwira. Migumisiro yekiriniki inosiyana uye kazhinji midiki.

Saka chirevo chekuzvisanganisa mubvunzo une musoro une mhinduro isingagutsi: hapana ongororo yakaburitswa, muyedzo wekiriniki, kana nhevedzano yenyaya dzevarwere yakawanikwa pachinyorwa chino yakaedza methylene blue pamwe chete nenicotinamide riboside, nicotinamide mononucleotide, kana NAD+ inopinzwa mutsinga. Ani naani anotsanangura kusanganisa uku sekunotsigirwa nehumbowo, kana sekunoita kuti zvinhu izvi zvisimbisane, ari kufungidzira kubva kumapoka maviri ehumbowo akasiyana.

Kufungidzira uku kunogona kukanganisa kumativi ose. Kunogona kuva netarisiro yakawandisa, kana huwandu hwose husina kumbova chinhu chaiganhurira mashandiro kana reshiyo yadzorerwa. Kunogonawo kurerutsa zvinhu zvakanyanya, nokuti mhinduro yemethylene blue pahuwandu hunopiwa inosvika painoshandukira kune rimwe divi. Vanoiongorora pachavo vanoitsanangura seine hormesis: mwero wakaderera unotsigira reduction, asi mwero wakakwirira unoendesa maerekitironi kure nemuketani wekufema kwesero uye unogona kukurudzira oxidation. Kuwedzera zvimwe zvinhu zvinoshandiswa mukuita uku hakuiti kuti hukama ihwohwo huve hwakachengeteka.

Panewo zvinonetsa pakudyidzana kwayo nezvimwe zvinhu zvisina chokuita neNAD+. Methylene blue inodzivisa monoamine oxidase A, ndosaka iine njodzi inoenderana neserotonin kana iri pamwe nemimwe mishonga yekuora mwoyo; wongororo yekukuvadza hurongwa hwepakati hwetsinga kwakataurwa yakawana kuti nyaya 13 pa14 dzaisangana nemaitiro eHunter ekuziva kukuvadzwa neserotonin. Inogonawo kukonzera methemoglobinemia kana muviri wasangana nehuwandu hwakakwirira. Kana uchitora mishonga inonyorerwa nachiremba, mubvunzo wekuzvisanganisa waunofanira kubvunza chiremba wako ndewenzira idzodzo, kwete wekuenzana kweredox. Kuchenjerera kumwe chete kunoshanda pakusanganisa kunowanzoitwa: zvimwe zviwedzerwa zvinotorwa pamwe chete nemethylene blue zvine humbowo hwazvo, husina kuedzwa zvakanyanya.

Nei kuchena kuchisarudza kuti uri kuita ongororo ipi chaizvo

Chigadzirwa chemethylene blue musanganiswa kusvikira rabhoritari yaratidza kuti handizvo. Tsvina yakakosha pano iAzure B, phenothiazine yakabviswa boka remethyl, isiri chinhu chisingashandi. Idhayi rinoshanda muredox rine hwaro hwakafanana hwemashandiro emagetsi nekemikari, saka chigadzirwa chine huwandu hunokosha hweAzure B hachisi kungova rudzi rwakachena kana rusina kuchena rwechinhu chimwe chete. Musanganiswa wakasiyana unoshanda panzira imwe chete, uine reshiyo isina munhu akatsanangura zvizere.

Giredhi reUSP ndiro rinoita kuti mutengi awane chinhu chakanyatsotsanangurwa. Chigadzirwa chisiri chegiredhi reUSP chinonyanya kunge chiri dhayi regiredhi remachira, uye magiredhi emachira ane tsvina inoita kuti asakodzere kunwiwa kana kudyiwa, kusanganisira simbi dzinorema nezvisaririra zvezvinonyungudutsa.

Musiyano hausi pakati pemagiredhi chete. Vatengesi vakawanda vanoti vanoenderana neUSP vanoongorora simbi dzinorema chete, vozoratidza boka iroro rimwe chete reongororo sekunge kuzadzisa zvinodiwa zvose. Zvinodiwa zvizere zvinosanganisira kuzivikanwa kwechinhu, kuchena, tsvina yezvinhu zveorganic, zvisaririra zvezvinonyungudutsa, tsvina yezvinhu zvemakemikari, zvisaririra mushure mekupiswa, miganhu yezvipenyu zvidiki, uye endotoxin dzemabhakitiriya. Boka reongororo risina kukwana harigoni kutaura pamusoro pezvarinosiya, uye zvinosiyiwa zvinosanganisira zvinhu zvine hukama nacho nezvisaririra zvezvinonyungudutsa.

Blupreme inotenga kubva kumugadziri wemethylene blue yemishonga uye inoburitsa chitupa cheongororo chinobata zvinodiwa zvose, kuitira kuti chinhu chiri mubhodhoro chive icho chinotsanangurwa netsvakurudzo. Kana uchida kuongorora kufunga uku wega usati watenga, maverengero etsvakurudzo yemethylene blue anotsanangura zvinogona uye zvisingagoni kuratidzwa nemhando imwe neimwe yeongororo.

Musiyano unoramba uripo kana wanyatsoongororwa

Kuwedzera chinotangira NAD+ kunoshandura kuti NAD+ iripo yakawanda sei. Methylene blue inoshandura zviri kuitwa neNAD+ yatovepo. Chekutanga mubvunzo wekuwanikwa kwezvinhu, chechipiri mubvunzo wekuyerera kwazvo, uye ongororo dzinotsigira chimwe hadzitauri zvakawanda pamusoro pechimwe.

Methylene blue inotsigirwa nemashandiro anotsanangurwa nenzira inowirirana, akasimbiswa mumitochondria yakaparadzaniswa uye mumatishu emhuka, aine muganhu wakajeka unogara uchidzokororwa: kushandura reshiyo hakuna kufanana nekugadzirisa tishu. Chainoshaya iongororo dzevanhu dzinoyera shanduko yeNAD+ muvanhu. Chinotadza kuwanikwa mumapoka ose maviri muyedzo wakananga wezvinhu zviviri izvi zvichitorwa pamwe chete.

Mapoka ose ari maviri anofanirwa kubatwa nenzira imwe chete. Bvunza kuti chigadzirwa chinoti chinoshandura chii, wozobvunza kuti ndezvipi zviyero zviripo zvechinhu ichocho muvanhu. Kana mhinduro iri ongororo yemasero, gonzo, kana nzira yemashandiro ine musoro, ndizvo zvayiri. Haisi musanganiswa wezviwedzerwa une humbowo.