Chinyorwa
Methylene blue seinodzivisa uye inokurudzira oxidation: chii chinoshandura mhedzisiro?
Fungidzira marabhoritari maviri achiedza dhayi rimwe chete rebhuruu oburitsa mhedzisiro inopesana. Mune rokutanga, mitochondria dzakabviswa muuropi dzinoshandisa oxygen zviri nani uye dzinogadzira ATP yakawanda. Mune rechipiri, gadziriro imwe cheteyo inoburitsa hydrogen peroxide yakawanda zvikuru. Mishumo yose iri miviri ndeyechokwadi. Inotsanangura kutenderera kumwe chete kunotariswa kubva kumativi maviri, uye kuvhiringidzika kunotanga apo vaverengi vanotora rimwe divi senyaya yose.
Chikanganiso kubvunza kuti izita ripi rinokodzera morekuru iri. Methylene blue inotambidza maerekitironi, sezvinoratidzwa nemapu ezvainonangana nazvo mukushanda kwemasero mumamiriro akakura. Dhayi raitwa oxidation rinogamuchira maerekitironi rova leucoMB isina ruvara. LeucoMB inotambidza maerekitironi iwayo mberi yodzokera pakuva yebhuruu. Zvaunoona zvinoenderana neanopa maerekitironi, anoagamuchira, uye kana hurongwa hwacho huchikwanisa kubvisa hydrogen peroxide inogadzirwa munzira. Mubvunzo unokosha hausi wokuti dhayi rinodzivisa oxidation here. Ndewokuti mamiriro acho anobvumira kutambidzwa kwemaerekitironi kuita chii.
Kutenderera kunoburitsa mativi ose ari maviri
Murima, kutenderera kukuru kupfupi. NADH, NADPH, kana zvinotakura maerekitironi muketani yekufema kwemasero zvinopa dhayi maerekitironi, zvichiriita reduction. Dhayi raitwa reduction rinobva rava nenzira dzinokwikwidzana dzokubudisa maerekitironi. Rinogona kutambidza maerekitironi ku cytochrome c rotsigira kufamba kwawo richipfuura parutivi pecomplex yakakuvadzwa; ndicho chikonzero kufema kwemasero nemusiyano wemagetsi pamembrane zvichidzorerwa zvishoma kana complex I kana III yavharwa. Kana kuti rinogona kutambidza maerekitironi zvakananga kuoxygen, izvo zvinodzorerazve chimiro chebhuruu zvichigadzira hydrogen peroxide. Nokuti dhayi rinodzorerazve chimiro charo, huwandu hushoma hunogona kudzokorora kutenderera uku kakawanda, huchiramba huchishandisa zvinopa maerekitironi uye huchiramba huchigadzira peroxide.
Dzimwe nzira mbiri dzinoshandura makemikari acho zvachose. Copper kana iron isina kusungirirwa inoshandura peroxide iyoyo inokwanisa kupararira kuita maoxidant anokuvadza zvakanyanya munzvimbo yaari, kuburikidza nekuita kwemakemikari kwerudzi rweFenton. Chiedza chitsvuku chinovhura imwe nzira inoshandisa chiedza kuita makemikari, umo dhayi rawedzerwa simba nechiedza rinotambidza simba kuoxygen rogadzira singlet oxygen, rudzi rwunotsanangurwa zvakadzama mutsananguro yephotochemistry yerudzi I nerudzi II. Kutenderera kweredox murima, kukuvara kunowedzerwa nesimbi, uye kukuvara kwephotodynamic inzira nhatu dzakasiyana dzinongotanga nemorekuru rimwe chete.
Tafura inobatanidza mamiriro nemhedzisiro
Tafura iri pasi ndiyo inokosha kuchengeta. Mutsara mumwe nomumwe une chinhu chimwe chinoshanduka, divi rachinosundira mhedzisiro, uye muyedzo unotsigira izvozvo. Yakanaka inoreva chiyero chinoratidza kudzivirirwa kana kuvandudzika. Yakashata inoreva oxidant yakawanda, kupera kukuru kwezvinhu zvinodiwa, kana kukuvara kwakawanda.
| Mamiriro | Divi remhedzisiro | Zvakaratidzwa nemuyedzo |
|---|---|---|
| Huwandu hushoma, 0.1 kusvika 1 uM, mitochondria dzakabviswa mumasero | Kuvandudzika kwesimba remasero pamwe neperoxide yakawanda | 0.1 uM yakavandudza kushandiswa kweoxygen mumitochondria dzemwoyo wemakonzo ane utano neane chirwere cheshuga; 100 nM kusvika 1 uM yakadzorera zvishoma ATP, musiyano wemagetsi pamembrane, uye kutorwa kwecalcium mumitochondria dzeuropi dzakanga dzavharwa, asi kuburitswa kweperoxide kwakawedzera mumamiriro ose |
| Huwandu hwakakwirira, pamusoro pe5 uM, masero asina kupiwa glucose | Chiratidzo chakashata cheoxidant | Masero eendothelium akaita oxidation kuchiratidziro cheROS chakajairika uye akarasikirwa neglutathione yakaitwa reduction pamusoro pe5 uM apo glucose yakanga isipo; kuwedzera glucose kwakadzivisa zvose zviri zviviri |
| Masubstrate ecomplex I (glutamate pamwe nemalate) | Peroxide yakawanda | Ongororo dzemitochondria dzeuropi nedzemwoyo dzose dzakawana kuburitswa kweperoxide kwakawedzera nemasubstrate akabatana neNADH |
| Succinate pamwe nerotenone, mitochondria dzemwoyo, 0.1 uM | Peroxide shoma mumaitiro iwayo emuyedzo | Ndicho chete chiyero cheperoxide muboka iri chakanyatsoratidza kudziviswa kweoxidation; cherechedza kuti maitiro emuyedzo aisanganisira rotenone uye tishu rakasiyana, saka substrate chete haitsananguri izvi |
| Chiedza chitsvuku, 20 uM pamwe ne630 nm | Kukuvara kwakashata kweDNA | Hapana kukuvara kwakakosha kweDNA yemitochondria murima pa20 uM; huwandu humwe chete nechiedza chitsvuku hwakakuvadza chidimbu chose chakaedzwa |
| Huwandu hwakanyanya kukwirira murima, 100 uM | Kukuvara kwakashata kweDNA kunosarudza nzvimbo | Kukuvara kweDNA yemitochondria kwaisarudza nzvimbo dzine purine yakawanda, shanduko huru kubva pachiratidzo cheperoxide chinowanikwa pahuwandu hwenanomolar |
| Copper kana iron pamwe neNADH, DNA isiri mumasero | Kukuvara kwakashata kunobva muoxidation | Copper yakanangisa kukuvara kunhevedzano yep53 iri panzvimbo inowanzokanganisika; iron EDTA yakakonzera kukuvara kwakapararira; catalase nezvinhu zvinosunga simbi zvakavhara nzira dzacho dzakatevedzana; guanine yakaitwa oxidation yakawedzera |
| Glucose iripo, masero asina kupatsanurwa | Kuderedzwa kwemhedzisiro kunodzivirira kunyange kutenderera kuchikurumidza | Glucose yakawedzera reduction yedhayi asi yakaderedza kushushikana kwese kwasara, zvinoenderana nokuti nzira yepentose phosphate inopa NADPH yokudzorerazve zvinodzivisa oxidation |
| Masero akaiswa ascorbate yakawanda | Zvakasanganiswa: ascorbate yakashandiswa, chiratidzo chebvunzo chakaderedzwa | Dhayi rakaramba richiita oxidation kuascorbate iri mukati memasero kunyange glucose iripo, richidzivisa oxidation yechiratidziro chebvunzo zvishoma; dura rezvinodzivirira ndiro rakabhadhara mutengo |
| Mhuka dzakatanga kurapwa nerotenone, dhayi richipiwa kutanga | Mhedzisiro yakanaka patishu | Kupa dhayi kare kwakaderedza kukuvara kweDNA yemitochondria kwakakonzerwa nerotenone muchikamu chepakati cheuropi hwembeva kunyange richiwedzera peroxide mumitochondria dzakabviswa mumasero |
Maitiro anooneka mumitsara yose ndiwo pfungwa huru. Kugadzirwa kweperoxide nekudzivirirwa kwezvinhu zvipenyu zvinhu zviviri zvakasiyana. Kurapwa kunogona kuratidza mhedzisiro yakashata pane chokutanga uye yakanaka pane chechipiri panguva imwe chete.
Nei huwandu humwe chete huchipa mhinduro dzakasiyana
Huwandu hunotara kukwanisa kutakura maerekitironi, kwete mhedzisiro yokupedzisira. Kuburitswa kweperoxide mumitochondria dzeuropi kwakawedzera zvichionekwa kubva pa50 nM zvichikwira muongororo yemitochondria dzeuropi dzisina kupatsanurwa, asi kukuvara kuri pachena kweDNA yemitochondria kwaida 100 uM murima. Ndiwo musiyano unopeta kanenge zviuru zviviri pakati pechiratidzo chokutanga nekukuvadza zvinhu zvemajini, asi hausiri muganhu wokuchengeteka. Zvinhu zvinoyerwa, zvikamu zvemaseru, nenguva yokusangana nedhayi zvakasiyana, saka nhamba idzi dzinoratidza zviitiko zvakasiyana pane kuva mapoinzi pagonyo rimwe chete. Hurukuro yemhinduro dzinoenderana nehuwandu inoisa musiyano wakadai pakati pechiratidzo chiduku nekukuvara kukuru mumamiriro akakura ehormesis.
Substrate ndiyo inotara panopinda maerekitironi. Zvinopa simba zvakabatana neNADH zvinopa dhayi zvakawanda zvinogona kupa maerekitironi, zvichitsigira zvose nzira inobatsira yokupfuura pakavharwa nekuita neoxygen kunopambadza. Pfupiso inowanzotaurwa yokuti succinate inoita kuti dhayi ridzivise oxidation asi glutamate ichiita kuti riikurudzire inodudzira data kupfuura zvarinoratidza, nokuti mamiriro ekuyera peroxide nesuccinate muongororo yemwoyo aivawo nerotenone uye akashandisa tishu nehuwandu zvakasiyana nezveongororo yeuropi yakawana peroxide yakawedzera pasubstrate yose nemamiriro ose ekufema.
Chiedza chinoshandura nzira yacho, kwete ukuru hwemhedzisiro chete. Musiyano wakajeka zvikuru muboka iri ndewokuti 20 uM murima haina kuita chinhu chaionekwa kuzvidimbu zveDNA yemitochondria, asi 20 uM muchiedza chitsvuku yakazvikuvadza zvose. Ani naani anoenzanisa muyedzo wakavhenekerwa newakaitwa murima ari kuenzanisa photochemistry nekutenderera kweredox.
Simbi dzinoshandura oxidant. Pasina simbi, kutenderera kwedhayi murima kunogadzira peroxide, morekuru rinokwanisa kupararira iro masero anoshandisawo sechiratidzo. Kana paine copper kana iron inowanikwa kuti iite makemikari, dhayi raitwa reduction neNADH rinopa maerekitironi kuita reduction yesimbi, uye simbi yaitwa reduction inoshandura peroxide kuita zvinhu zverudzi rwehydroxyl kana zvecopper peroxide pedyo neDNA. Ndiyo nzira iyo ongororo isina masero ichishandisa NADH nemaion esimbi yakaburitsa kukuvara kweDNA kwaisarudza nzvimbo dzinowanzokanganisika pamwe nekukuvara kwakapararira kubva mudhayi rimwe chete rokutanga. Mabatiro esimbi muchikamu chacho, kwete dhayi chete, ndiwo anotara kana nzira iyi ichikosha.
Kuwanikwa kwezvinopa simba ndiko kunotara kana sero richikwanisa kubhadhara mutengo. Mumasero eendothelium akaiswa mudhayi re2 kusvika 20 uM, kubvisa glucose kwakaratidza mutengo weoxidant asi kupa glucose kwakaupedza, kunyange glucose yaikurumidzisawo reduction yedhayi. Kutenderera kunokurumidza kuine zvinotsigira dziviriro kuri nani kupfuura kutenderera kunononoka pasina dura redziviriro. Ona chirevo chipi nechipi cheoxidant chisingatauri mamiriro eglucose kana NADPH sechisina kukwana.
Tishu ndiro rinotara midziyo iripo. Masero eendothelium anogadzirazve NADPH kuburikidza nekugayiwa kweglucose uye ane matura ezvinodzivisa oxidation mucytosol. Mitochondria dzakabviswa mumasero hadzina zvose izvozvo. DNA yakacheneswa haina kunyange nzira dzokuzvigadzirisa. Mhedzisiro mune imwe gadziriro inofanotaura zvishoma nezvedzimwe, ndicho chikonzero chinyorwa chakarongwa pamusoro pemhinduro dzinosiyana netishu chichafanira kuchengeta hurongwa uhu hwakaparadzana.
Kuyera zvakananga hakusi kuyera dziviriro inouya pashure
Zvinyorwa zvakawanda zvinosanganisa nhanho mbiri dzinochengetwa dzakaparadzana nemiyedzo. Imwe nhanho inobvunza kuti oxidant yakawanda sei yakaoneka. Imwe inobvunza kuti sero rakapindura sei.
Bvunzo dzeperoxide dzerudzi rweAmplex ndidzo dziri pedyo zvikuru nenhanho yokutanga, asi kunyange idzo dzinoratidza kuyerera kwasara, kureva kugadzirwa kubvisa kuparadzwa kubvisa kubudiswa kunze. Ongororo yemitochondria dzeuropi yakawana kuti mativi ose ari maviri akanga achichinja: peroxide yakawanda yaigadzirwa uye peroxide yakawedzerwa kamwe chete yaibviswa zvishoma nezvishoma. Mberi mune zvinoitika pashure pane oxidation yeglutathione, kushandiswa kweascorbate, guanine yakaitwa oxidation, uye kukuvara kweDNA kunovharidzira polymerase. Nhanho imwe neimwe inowedzera zviitiko zvemaseru pakati peoxidant nechiyero chinobuda.
Maenzayimu anodzivisa oxidation anotungamirirwa neNrf2 pamwe nekugadzirwa kwemitochondria matsva zviri munhanho yechipiri. Zvirongwa zvokujairana nemamiriro zvinogona kutangwa nekuwedzera kuduku kweperoxide kwenguva pfupi, uye vanyori veongororo yokudzivirirwa kwemitochondria dzeuropi vanokurudzira chaizvo pfungwa yokuti kushushikana kuduku uku ndiko kunotanga mhinduro vachicherechedza kuti ketani yezvinokonzera mhedzisiro kuburikidza neNrf2 yakavakirwa paongororo dzakaitwa kare, kwete pakuratidza kwavo kwakakwana. Dziviriro inosvika maawa akati gare gare kuburikidza nemapuroteni matsva hairevi kuti makemikari akatanga izvi aidzivisa oxidation. Zvinoreva kuti chiitiko chiduku chinokurudzira oxidation chakatenga dziviriro yakakura. Miganhu inobatsira pakuverenga zvirevo zvakadaro, kusanganisira miganhu yebvunzo nemisiyano yegadziriro, ndiyo nyaya yegwara rokuverenga tsvakurudzo yemethylene blue.
Nei bvunzo dzichipesana
Chiratidziro chebvunzo chakajairika chakadai sedihydrofluorescein chinoratidza oxidation yakafara yechiratidziro chacho, kwete huwandu hweperoxide. Chinoenderana nemakemikari eperoxidase neheme uye chinogona kutadza kuona kuwedzera kweperoxide kunoonekwa nebvunzo yeAmplex yakagadziridzwa kuti iyere nemazvo. Ongororo yemitochondria dzeuropi yakaona peroxide yakawedzera zvikuru pasina chiratidzo chesuperoxide chinofambirana nayo, inova yambiro pamusoro pokungotaura chirevo chimwe chete chekudzivisa oxidation chakavakirwa padhayi. Kupindirana kwezviratidzo zvechiedza mubvunzo wakakodzera kuongororwa mumiedzo yokudzora, nokuti dhayi rinotora chiedza chinooneka pedyo nenzvimbo dzinowanzoshandiswa kumutsa nokuburitsa chiedza. Asi ongororo yakaitwa nokungwarira yakagadziridza zviyero ichienzanisa neperoxide yaizivikanwa huwandu hwayo, yakaderedza nguva yokuvhenekerwa nechiedza chinomutsa chiratidzo pasina shanduko huru muchiratidzo, uye yakasimbisa kubviswa kweperoxide kunononoka ichishandisa erekirodhi yakasiyana. Kupindira pachiyero chinhu chinofanira kuedzwa nemuyedzo wokudzora, kwete chikonzero chokuramba mhedzisiro pasina kuiongorora.
Mhedzisiro yecalcium inoratidza kudikanwa kumwe chete uku kwokutaura nemazvo. Dhayi rakapiwa kwenguva pfupi harina kushandura calcium yose yakatorwa pamberi pekuchinja kwekupindika kwemembrane muongororo yemwoyo, asi rakavandudza kumhanya kwekutorwa kwecalcium mumitochondria dzeuropi dzakanga dzavharwa muongororo yemitochondria dzemwoyo yakatarisa chirwere cheshuga. Zvinoyerwa zvakasiyana, hurongwa hwakasiyana, hapana kupesana.
Rondedzero yokutarisa usati wavimba nemutongo
Tora mutongo wose wokuti chinhu chinodzivisa kana kukurudzira oxidation somushumo pamusoro pehurongwa hwakati, wobvunza mibvunzo mishanu. Pahuwandu hupi, uye muchikamu chipi. Pachishandiswa chii chinopa maerekitironi uye chii chinokwikwidzana pakuagamuchira. Muchiedza kana murima, uye pawavelength nehuwandu hupi hwechiedza. Paine simbi dzipi dzinowanikwa uye matura api ezvinopa simba nezvinodzivisa oxidation ari kutsigirwa. Uye nebvunzo ipi, ichiyera kuyerera kweoxidant kana kukuvara kana mhinduro yokujairana nemamiriro. Shandura mhinduro imwe chete uye morekuru rimwe chete rinogona kufamba mutafura kubva pakudzivirira kuenda pakukuvadza pasina chinhu chinopikisana zvachose.