▎ 5-Amino-1MQ Kev Tshawb Fawb
Dab tsi yog qhov kev tshawb fawb keeb kwm ntawm 5-Amino-1MQ?
Hauv kev hloov pauv ntawm kev noj qab haus huv hauv metabolic thiab kev tshawb fawb txog kev ua neej ntev, kev txheeb xyuas cov kev cuam tshuam zoo los daws cov teeb meem metabolic thiab ncua kev laus tseem yog qhov tseem ceeb hauv kev tshawb fawb. Nicotinamide N-methyltransferase (NNMT) muaj kev ua haujlwm siab hauv cov ntaub so ntswg adipose thiab daim siab. Los ntawm methylating nicotinamide, nws txo nws txoj kev hloov mus rau nicotinamide adenine dinucleotide (NAD⁺). NAD⁺ yog ib qho tseem ceeb rau cellular basal metabolism, lub zog tsim, kho DNA, thiab kev taw qhia txoj hauv kev. Kev tswj hwm nws cov qib zoo yog qhov tseem ceeb rau kev noj qab haus huv ntawm tes thiab tiv thaiv kev laus thiab kev ua haujlwm tsis zoo ntawm cov metabolism. Hauv 2017, cov kws tshawb fawb ntawm University of Texas thawj zaug tshawb xyuas 5-Amino-1MQ thaum nrhiav txoj hauv kev los tiv thaiv NNMT. Muab NNMT lub koom haum muaj zog nrog kev rog rog thiab ntshav qab zib hom 2, cov kws tshawb fawb pom tias kev thaiv NNMT tuaj yeem qhib txoj hauv kev tshiab los kho kev rog rog thiab nws cov teeb meem metabolic. Qhov no tau tsim qhov tseem ceeb rau kev tshawb fawb 5-Amino-1MQ.
Dab tsi yog qhov txheej txheem ntawm kev txiav txim rau 5-Amino-1MQ?
Inhibiting cervical cancer cell proliferation: 5MQ yog ib qho me me-molecule inhibitor ntawm nicotinamide N-methyltransferase (NNMT) uas nthuav tawm cov teebmeem tseem ceeb ntawm HeLa epithelial cervical carcinoma cell kab, nrog rau cov nyhuv no yog concentration- thiab lub sij hawm-dependent. NNMT yog ib qho enzyme metabolic cuam tshuam nrog qog nqaij hlav thiab metastasis. Los ntawm inhibiting NNMT, 5MQ yuav cuam tshuam ntau txoj hauv kev hauv nruab nrog cev uas txuas rau qog kev loj hlob. Piv txwv li, 5MQ tuaj yeem cuam tshuam nrog nicotinamide metabolism-txog txoj hauv kev. Kev tsis sib haum xeeb hauv nicotinamide metabolism tuaj yeem cuam tshuam ntxiv rau cov cellular zog metabolism, kho DNA, thiab lwm yam txheej txheem, yog li inhibiting mob qog noj ntshav cell proliferation. Hauv kev sim, raws li 5MQ concentration nce thiab kev kho lub sijhawm txuas ntxiv, HeLa cell proliferation tau nthuav tawm cov lus qhia ntxiv. Raws li qhov tshwm sim, kev hloov pauv morphological suav nrog cell shrinkage, poob ntawm intercellular adhesion, thiab lub cev apoptotic tau pom, qhia tias 5MQ induces apoptosis, yog li suppressing cell proliferation [1].
Kev tswj hwm ntawm Gene thiab Protein Expression: Tom qab 5MQ kho ntawm HeLa hlwb, mRNA qib ntawm ZEB1, SIRT1, thiab CD16 tau nce, thaum TWIST thiab SERPIN1 mRNA qib qis. Tib lub sijhawm, kev qhia ntawm oncogenic proteins phospho-Akt thiab SIRT1 poob qis. Cov noob thiab cov proteins no ua lub luag haujlwm tseem ceeb hauv cov qog nqaij hlav thiab kev loj hlob. Piv txwv li, TWIST thiab SERPIN1 feem ntau cuam tshuam nrog qog nqaij hlav thiab metastasis. Los ntawm kev txo lawv cov lus qhia, 5MQ tuaj yeem cuam tshuam cov peev xwm cuam tshuam thiab metastatic ntawm HeLa hlwb. Txawm hais tias mRNA qib ntawm ZEB1 thiab SIRT1 tau nce, qhov kev qhia ntawm oncogenic protein SIRT1 poob qis. Qhov no yuav tshwm sim vim hais tias 5MQ cuam tshuam rau cov kev cai tom qab transcriptional, inhibiting SIRT1 protein muaj nuj nqi thiab yog li cuam tshuam rau cell proliferation thiab ciaj sia taus. Phosphorylated Akt plays lub luag haujlwm tseem ceeb hauv kev muaj sia nyob ntawm tes, kev loj hlob, thiab kev tswj hwm metabolic. 5MQ qhov txo qis hauv nws cov lus qhia tuaj yeem cuam tshuam cov qog nqaij hlav qog noj ntshav thiab kev muaj sia nyob los ntawm kev thaiv cov kev taw qhia ntsig txog [1].
Dab tsi yog daim ntawv thov ntawm 5-Amino-1MQ?
Hauv kev tshawb fawb txog kev noj qab haus huv metabolic, nws txoj haujlwm tseem ceeb yog los kho cov cellular metabolic tshuav nyiaj los ntawm inhibiting NNMT. NNMT noj nicotinamide (ib tug precursor ntawm NAD⁺) thiab cuam tshuam methyl pub metabolism, thaum 5-Amino-1MQ thaiv cov txheej txheem no: ntawm ib sab, nws txo cov nicotinamide methylation noj nyob rau hauv adipocytes, elevating intracellular NAD⁺ qib kom qhib NAD⁺ RT (ntev-siv) thiab optimizes mitochondrial muaj nuj nqi - txheej txheem uas txhawb lipolysis, inhibits lipogenesis, pab tswj lub zog metabolism hauv cov ntaub so ntswg adipose, thiab txo cov rog ntau dhau. Ntawm qhov tod tes, nws kuj txo qis insulin tsis kam uas feem ntau pom nyob rau hauv cov kab mob metabolic los ntawm kev txhim kho insulin teeb liab txoj kev rhiab heev, thaum muaj feem cuam tshuam ncaj qha rau kev tswj cov kab mob siab gluconeogenesis los pab tswj cov ntshav qabzib. Tsis tas li ntawd, nws muaj peev xwm cuam tshuam rau lub plab microbiota yog nyob rau hauv kev tshawb nrhiav, nrog kev xav tias nws tuaj yeem txhawb nqa tag nrho cov metabolic homeostasis los ntawm kev tswj hwm microbial metabolic kev ua si (xws li, txo qis cov khoom noj metabolite).
Hauv kev tshawb nrhiav mob qog noj ntshav, nws daim ntawv thov tsom mus rau lub hom phiaj ntawm 'metabolic vulnerability' ntawm cov qog hlwb. Txhawm rau kom muaj kev loj hlob sai, cov qog hlwb feem ntau vam khom rau txoj hauv kev ua haujlwm tsis zoo (xws li cov nyhuv Warburg), thiab NNMT tau qhia ntau heev hauv qee cov qog hlwb, txhawb lawv cov metabolism. Los ntawm inhibiting NNMT, 5-Amino-1MQ cuam tshuam cov qog cell metabolism hauv ob txoj hauv kev: Ua ntej, nws txo qis hauv cov qib NAD⁺, cuam tshuam lub zog tsim, ua rau lub zog tsis txaus thiab biosynthetic substrates xav tau rau kev loj hlob; Qhov thib ob, nws cuam tshuam rau kev siv cov methyl pub dawb, cuam tshuam cov txheej txheem kev tswj hwm epigenetic zoo li DNA methylation hauv cov qog hlwb, yog li inhibiting gene qhia cuam tshuam nrog kev loj hlob thiab metastasis. Tsis tas li ntawd, nws tuaj yeem cuam tshuam tsis ncaj qha rau cov qog loj hlob thiab kis tau los ntawm kev hloov pauv cov txheej txheem metabolic hauv cov qog microenvironment, muab lub hauv paus rau kev tshawb nrhiav cov qog metabolic cuam tshuam.
Raws li cov cuab yeej tshawb fawb tseem ceeb, nws yog ib txoj hauv kev tseem ceeb rau kev txiav txim siab NNMT lub cev muaj zog. Cov kws tshawb fawb tuaj yeem tiv thaiv NNMT kev ua tau zoo siv 5-Amino-1MQ hauv cellular lossis tsiaj qauv los soj ntsuam cov kev hloov pauv hauv cov ntsuas metabolic. Piv txwv li, hauv kev sim ntawm tes, saib xyuas NAD⁺ concentrations, qib methyl pub dawb, thiab kev ua haujlwm ntawm cov enzymes koom nrog fatty acid synthesis tuaj yeem qhia meej NNMT lub luag haujlwm tshwj xeeb hauv cellular metabolism. Hauv cov qauv tsiaj, ua ke nrog cov ntaub so ntswg tshwj xeeb kev soj ntsuam, nws ua rau kev tshawb fawb ntawm NNMT cov ntaub so ntswg tshwj xeeb ua haujlwm-xws li nws cuam tshuam rau cov metabolism hauv siab thaum laus lossis nws cov kev tswj hwm lub zog hauv cov neurons. Tsis tas li ntawd, leveraging cov lus teb sib txawv ntawm cov kab ntawm tes (xws li, cov hlwb ib txwm qhia tias tsis tshua muaj rhiab heev tiv thaiv cov lus teb hauv cov kab mob metabolically txawv txav lossis qog hlwb) tuaj yeem pab hauv kev txiav txim siab cov txheej txheem ntawm cov cellular metabolic, qhia cov kev tshawb fawb tom ntej.
Hauv cov thawj coj ntawm cov leeg nqaij noj qab haus huv thiab kev paub, nws daim ntawv thov chaw nyob ntawm 'zog metabolism - cellular function' kev sib raug zoo. Hauv kev tshawb fawb txog kev noj qab haus huv ntawm cov leeg nqaij, kev kho cov leeg yog nyob ntawm kev ua kom muaj zog thiab kev loj hlob ntawm cov hlwb satellite, cov txheej txheem yuav tsum muaj lub zog txaus. -5-Amino-1MQ txhawb nqa lub xov tooj ntawm tes ua haujlwm los ntawm kev tswj cov qib NAD⁺ hauv cov leeg nqaij. Ib txhij, nws optimizes mitochondrial muaj nuj nqi los txhim kho cov leeg nqaij zog metabolism efficiency, alleviating rov qab kev nyuaj siab tom qab-muscular raug mob. Nws kuj tseem tuaj yeem txo oxidative kev ntxhov siab hauv cov leeg nqaij, tiv thaiv cov hlwb los ntawm kev puas tsuaj los ntawm cov khoom siv metabolic ntau dhau. Hauv kev tshawb fawb txog kev txawj ntse, lub hlwb neurons muaj qhov xav tau lub zog siab heev, thiab txo qis NAD⁺ qib cuam tshuam nrog kev ua haujlwm ntawm neural poob. 5-Amino-1MQ khaws cia neuronal NAD⁺ muab los ntawm inhibiting NNMT, yog li tiv thaiv mitochondrial muaj nuj nqi thiab txo cov neuroinflammation. Nws kuj tseem tuaj yeem cuam tshuam cov neurotransmitter metabolism (ntawm NAD⁺-dependent enzymes koom nrog hauv neurotransmitter synthesis) los txhawb kev paub txog kev ua haujlwm neuronal (piv txwv li, cellular muaj nuj nqi hauv kev kawm / nco thaj chaw xws li hippocampus), muab cov kev xav tshiab rau kev paub txog kev ua haujlwm txij nkawm.
Xaus
Raws li ib qho tshwj xeeb inhibitor ntawm nicotinamide N-methyltransferase (NNMT), 5-Amino-1MQ qhia tus nqi tseem ceeb thoob plaws ntau lub tebchaws los ntawm kev tsom mus rau NNMT-txheej txheem metabolic txoj hauv kev. Nws tuaj yeem txhim kho kev rog thiab insulin tsis kam los ntawm kev tswj hwm qib NAD⁺, txhim kho cov haujlwm ntawm mitochondrial, thiab rov ua kom cov metabolism hauv kev sib npaug. Nws kuj tseem tsom rau cov teeb meem metabolic hauv cov qog nqaij hlav, cuam tshuam lawv lub zog tsim khoom thiab kev tswj hwm epigenetic kom inhibit qog kev loj hlob. Tsis tas li ntawd, nws ua haujlwm raws li cov cuab yeej tshawb fawb rau elucidating NNMT muaj nuj nqi thaum ua kom pom lub luag haujlwm hauv kev kho cov leeg nqaij thiab kev paub txog kev noj qab haus huv, muab cov lus qhia tseem ceeb rau kev cuam tshuam kev tshawb fawb hauv cov kab mob metabolic, mob qog noj ntshav, thiab lwm yam mob.
Hais Txog Tus Sau
Cov ntaub ntawv hais saum toj no yog txhua yam tshawb fawb, kho thiab sau los ntawm Cocer Peptides.
Scientific Journal Author
Akar s yog tus kws tshawb fawb uas nws txoj haujlwm tsom mus rau cov txheej txheem molecular thiab cov kev pabcuam kho mob. Nws tau pab txhawb rau kev tshawb fawb tshawb xyuas lub luag haujlwm ntawm cov enzymes thiab cov tshuaj tiv thaiv me me hauv kev tswj cov cellular proliferation. Nws txoj kev tshawb fawb qhia txog qhov tseem ceeb ntawm kev tsom mus rau txoj hauv kev metabolic, xws li nicotinamide N-methyltransferase, txhawm rau tshawb nrhiav cov tswv yim tshiab biomedical.Akar s tau teev nyob rau hauv cov ntaub ntawv siv los ntawm citation [2].
