EchinacosideTiv thaiv MPP ntxiv -Induced Neuronal Apoptosis ntawm ROS/ATF3/CHOP Txoj Cai

Qing Zhao1 • Xiaoyan Yang2 • Dingfang Cai3,4 • Ling Ye5,6 • Yuqing Hou1 •

Lijun Zhang1 • Jiwei Cheng1 • Yuan Shen1 • Kaizhe Wang5 • Yu Bai1

Hu rau:joanna.jia@wecistanche.com

Pls nyem qhov no mus rau Ntu 2

Echinacosidelos ntawm Cistanche deserticola muaj cov nyhuv ntawminhibiting apoptosis

Kev sib tham

ECH yog ib qho ntawm cov nquag tshaj plawsphenylethanoid glycosideskoom nrog hauv kev tiv thaiv oxidant thiab dawb-radical scavenging [26]. Ntau qhov kev tshawb fawb tau pom tias nws tseem ceeb txhim kho tus cwj pwm ntawm lub cev muaj zog thiab txo qis kev poob ntawm nigral DA neurons hauv MPTP-

lesioned nas, Lwm cov txiaj ntsig tau pom tiasECHtiv thaiv cov neurons los ntawm inhibiting active caspase-3/8 nyob rau hauv cerebellar granule hlwb thiab txhim khu kev qhia ntawm GDNF thiab hlwb-derived neurotrophic yam hauv SNc [10, 11]. Cov ntaub ntawv los ntawm kev tshawb fawb tam sim no tau pom tiasECHncaj qha inhibits MPP?-induced ROS ntau lawm hauv SH-SY5Y neuroblastoma hlwb. ROS yog ib qho ntawm cov khoom ntawm cellular zog metabolism. Nyob rau hauv ib txwm muaj mob, superoxide dismutase thiab lwm yam antioxidants tiv thaiv thiab inhibit qhov tsub zuj zuj ntawm ROS [27]. Nws paub zoo tias mitochondria yog lub hauv paus tseem ceeb ntawm cellular ROS, thiab ROS tiam yog txuam nrog mitochondrial morphology thiab kev ua haujlwm [28]. Cov kev tshawb fawb tsis ntev los no tau tshaj tawm tias kev puas tsuaj mitochondrial thiab cov khoom ROS tuaj yeem koom nrog MPP?-induced apoptosis hauv SH-SY5Y hlwb [7, 29]. Cov kev tshawb fawb tam sim no tau qhia tias kev tiv thaiv cov qauv mitochondrial lossis cov txheej txheem mitochondrial tshem tawm cov apoptosis ntxias los ntawm MPP? [29, 30] ib. Ntau qhov kev tshawb fawb tau pom tiasECHtiv thaiv cell ciaj sia nyob rau hauv txawv PD qauv ntawm kev thaiv cov mitochondrial puas los ntawm MPP? [13, 21] ib. Kev tshawb fawb tsis ntev los no qhia tias MPP? yog ib feem lub luag haujlwm rau cov necrosis hauv SH-SY5Y hlwb [31]. Hauv thawj DA neurons, MPP? induces necrosis los ntawm kev ua kom cov lus qhia thiab tso tawm ntawm TNF-a thiab IL-1b thiab txo cov kev qhia thiab tso tawm ntawm cov tshuaj insulin zoo li kev loj hlob -1 [32]. Ntau cov kev tshawb fawb qhia tias apoptosis yog qhov tseem ceeb ntawm MPP?- induced SH-SY5Y cell tuag. Peb cov ntaub ntawv kuj txhawb nqa qhov kev xav no (Daim duab 4, 9).

Cov hlwb uas raug cuam tshuam nrog ROS ntau dhau tuaj yeem tsim teeb meem loj, suav nrog kev puas tsuaj rau cov kab mob lipid, kev hloov pauv hauv cov protein thiab folding, thiab nce genome instability [33]. Thaum kawg, ntau dhau ROS induces transcription ntawm apoptosis-txuas nrog cov noob, thaum kawg ua rau apoptosis lossis tuag.

[34, 35] ib. ATF3 thiab CHOP yog ob ntawm cov noob tseem ceeb tshaj plaws rau ROS-vim cov lus teb rau kev ntxhov siab. Cov kev tshawb fawb tsis ntev los no tau qhia MPP?-induced ATF3 thiab CHOP qhia hauv cov hlwb neuroblastoma [9, 23]. ATF3 upregulates p53 qhia thiab induces apoptosis hauv SH-SY5Y hlwb [23] thiab lwm cov hlwb [17, 36]. Qhov zoo siab, kev tshawb fawb tsis ntev los no tau pom tias ATF3 upregulation ntawm p53 plays lub luag haujlwm tseem ceeb hauv apoptosis induced los ntawm MPP? [36]. CHOP yog thawj zaug tau txheeb pom tias yog ib qho kev hloov pauv uas tau tshwm sim hauv kev teb rau kev loj hlob raug ntes thiab DNA puas. ATF3 tswj CHOP qhia thiab koom nrog CHOP los hloov kho apoptosis [37, 38]. Peb cov txiaj ntsig tau pom tiasECHPuas muaj kev txwv tsis pub ATF3 qhia nrog lossis tsis muaj MPP? (Daim duab 3A) thiab tseem inhibit MPP?-induced apoptosis (Fig. 4A). Dhau li ntawm CHOP,ECHkuj suppressed p53 thiab PUMA qhia hauv cellular qauv ntawm PD (Fig. 7). Cov txiaj ntsig no qhia tias ECH ua lub luag haujlwm hauv kev hloov pauv ntawm ATF3 qhia.

Cistancheechinacoside cov tshuajmuaj cov nyhuv ntawm kev txhim khotiv thaiv kab mob

Peb cov txiaj ntsig kuj tau pom tias ATF3 down-regulation los ntawm shRNA qhov tseem ceeb txo qis CHOP qhia thiab cov cleaved caspase-3 qib uas yav dhau los induced los ntawm MPP? (Daim duab 6C). Qhov no qhia tias ATF3 ua lub luag haujlwm hauv MPP?-induced apoptosis ntawm SH-SY5Y hlwb. Nyob rau hauv daim duab 11 Cov txheej txheem tsim los ntawm kev tiv thaiv ntawmECHtiv thaiv MPP?-induced apoptosis hauv SH-SY5Y hlwb.ECHattenuates ROS tsim induced los ntawm MPP?, thiab nyob rau hauv lem downregulates qhov kev qhia ntawm ATF3 thiab CHOP. ECH kuj ncaj qha inhibits ATF3 qhia. Lwm ceg qhia tau hais tias ECH txhawb txoj kev qhia ntawm anti-apoptosis protein, GDNF, hauv MPP?-kho hlwb. ATF3 tswj cov kev qhia ntawm pro-apoptosis proteins p53 hauv PD cell qauv thiab. Tag nrho cov kev ua no ua rau muaj kev tiv thaiv ntawm ECH tiv thaiv apoptosis ntxias los ntawm MPP?.

Ntxiv rau, cov txiaj ntsig tau pom tiasECHtxhim kho GDNF qhia tom qab MPP? kev kho mob hauv SH-SY5Y hlwb (Fig. 3B). GDNF yog ib qho tseem ceeb rau kev ciaj sia rau cov neurons [14]. Cov txiaj ntsig hauv vitro no zoo ib yam nrog cov ntaub ntawv los ntawm cov qauv tsiaj [14].

Ua ke, cov txiaj ntsig los ntawm txoj kev tshawb fawb tam sim no qhia tau tias txoj hauv kev ROS / ATF3 / CHOP plays lub luag haujlwm tseem ceeb hauv kev tiv thaiv kev tiv thaiv.ECHtawm tsam DA cell apoptosis induced los ntawm MPP?, nthuav tawm cov txheej txheem tshiab rauECHneuroprotection hauv ib qho qauv hauv vitro ntawm PD (Fig. 11).

Cistancheechinacoside muaj ib qhoanti-inflammatorynyhuv

Kev lees paub Txoj haujlwm no tau txais kev txhawb nqa los ntawm National Natural Science Foundation ntawm Tuam Tshoj (81202814), Shanghai Municipal Commission of Health thiab Family Planning (20124y116), thiab Cov Tub Ntxhais Kawm Qhia Kev Kawm Nyiaj Txiag Scheme ntawm Shanghai Colleges thiab Universities, Tuam Tshoj (zzszy12026). Peb ua tsaug rau Dr. Yunsheng Yuan, xibfwb Dazheng Wu, thiab Associate Professor Peihao Yin rau lawv cov kev taw qhia txog kev sim thiab kev npaj cov ntawv sau.

Cistancheechinacoside cov tshuajmuajneuroprotectiveteebmeem

Cov ntaub ntawv

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