分子毒理通路發(fā)現(xiàn)者PCR芯片
| 地區(qū)： | 上海 |
| 簡介： | 上海 |
| 提供商： | SABio |
| 服務(wù)名稱： | PCR 芯片 |
分子毒理通路發(fā)現(xiàn)者PCR芯片可用于研究與13個(gè)被藥物毒性激活的生物學(xué)通路中的370個(gè)關(guān)鍵基因的表達(dá)。在藥物處理后的細(xì)胞系或組織（肝臟）中進(jìn)行這些基因的表達(dá)情況的檢測，可以找到該藥物誘導(dǎo)的毒理反應(yīng) ，包括編碼電子轉(zhuǎn)運(yùn)鏈以及氧化磷酸化復(fù)合物組成蛋白的基因。了解這些機(jī)制可以幫助我們對藥物的化學(xué)結(jié)構(gòu)進(jìn)行修改來避免藥物的毒性反應(yīng)，而不是完全地否定某個(gè)對疾病有治療或者預(yù)防作用的藥物。這張芯片上所有的毒性反應(yīng)通路，可以是獨(dú)立的也可以是相互關(guān)聯(lián)的。例如，β-氧化導(dǎo)致脂肪變性，線粒體能量代謝解偶聯(lián)導(dǎo)致細(xì)胞的凋亡和壞死。影響活性氧代謝或細(xì)胞的氧化還原反應(yīng)的藥物會(huì)引起氧化應(yīng)急和抗氧化系統(tǒng)的相應(yīng)。這些反應(yīng)性的藥物可能在極端情況下通過活化DNA損傷信號以及DNA修復(fù)，細(xì)胞凋亡和壞死的信號通路，直接損傷DNA或者抑制DNA的修復(fù)。干擾蛋白質(zhì)合成的過程，會(huì)引起內(nèi)質(zhì)網(wǎng)應(yīng)激，激活未折疊的蛋白放映，上調(diào)熱休克蛋白和伴侶基因的表達(dá)。細(xì)胞色素P450以及其他第一階段的藥物代謝酶會(huì)在藥物抑制其化學(xué)修飾活性的情況下表達(dá)量升高。在更為嚴(yán)重的情況下藥物抑制脂肪酸和脂質(zhì)代謝，包括膽汁淤積，脂質(zhì)貯積癥以及磷脂質(zhì)病。藥物對免疫系統(tǒng)細(xì)胞的毒性反應(yīng)可以引起免疫抑制或者免疫毒性。利用實(shí)時(shí)定量PCR，研究者可以方便并且可信地對藥物的毒理反應(yīng)通路相關(guān)的基因進(jìn)行同時(shí)檢測。 Apoptosis: ABL1, AKT1, APAF1, BAD, BAK1, BAX, BCL2, BCL2L1 (BCL-X), BCL2L11, BID, BIRC3 (c-IAP1), CASP1 (ICE), CASP3, CASP7, CASP8 (FLICE), CASP9, CD40 (TNFRSF5), CD40LG (TNFSF5), CFLAR (CASPER), FADD, FAS (TNFRSF6), FASLG (TNFSF6), GADD45A, MCL1, TNF, TNFRSF10A, TNFRSF10B (DR5), TNFRSF1A, TNFSF10 (TRAIL), TP53, XIAP. Necrosis: ATP6V1G2, BMF, CCDC103, CD300LD, CLEC18A, COMMD4, CYLD, DEFB1, DPYSL4, EIF5B, FOXI1, GALNT5, GRB2, HOXA3, HSPBAP1, JPH3, KCNIP1, MAG, NUDT13, OR10J3, PARP2, PVR, RAB25, S100A7A, SPATA2, SYCP2, TMEM57, TNFAIP8L1, TNFRSF1A, TXNL4B. DNA Damage & Repair: APEX1, ATM, ATR, BRCA1, BRCA2, CDKN1A (p21CIP1/WAF1), CHEK1, CHEK2 (RAD53), DDIT3 (GADD153/CHOP), ERCC1, ERCC2 (XPD), ERCC3 (XPB), ERCC5, ERCC6, GADD45A, LIG4, MDM2, MGMT (AGT), MLH1, MSH2, OGG1, PARP1 (ADPRT1), PCNA, PRKDC, RAD51, TP53, XPA, XPC, XRCC1, XRCC5. Mitochondrial Energy Metabolism: ACLY, ACO1, ACO2, COX6B1, COX8A, CS, CYC1, DLD, DLST, FH, IDH1, IDH2, IDH3A, IDH3B, IDH3G, MDH1, MDH1B, MDH2, OGDH, SDHA, SDHB, SDHC, SDHD, SUCLA2, SUCLG1, SUCLG2, UCP1, UCP2, UCP3. Fatty Acid Metabolism (?-Oxidation): ACAA1, ACAA2, ACAD11, ACAD9, ACADL, ACADM, ACADS, ACADSB, ACADVL, ACAT1, ACAT2, ACOT1, ACOT12, ACOT6, ACOT7, ACOT8, ACOT9, ACOX1, ACOX2, ACOX3, BDH2, CPT1A, CPT1B, CPT2, CRAT, CROT, DECR1, ECHS1, EHHADH, GCDH, HADHA. Oxidative Stress & Antioxidant Response: AASS, CAT, CTSB, DHCR24, DUOX1, DUOX2, EPX, GPX1, GPX2, GPX3, GPX4, GPX5, GPX6, GPX7, IDH1, MPO, NQO1, NUDT1, NUDT15, PPP1R15B, PRDX1, PRDX2, PRDX6 (AOP2), SOD1, TPO, TXNIP, TXNRD2, UCP3. Heat Shock Response: CRYAA, CRYAB, DNAJA1, DNAJA2, DNAJA3, DNAJB1, DNAJB6, DNAJC3, DNAJC5, DNAJC6, HSF1 (TCF5), HSF2, HSP90AA1, HSP90AB1, HSP90B1 (TRA1), HSPA1A, HSPA1B, HSPA1L, HSPA2, HSPA4 (HSP70), HSPA5 (GRP78), HSPA8, HSPA9, HSPB1 (HSP27), HSPB2, HSPB6, HSPB8, HSPD1, HSPE1, HSPH1 (HSP105), TCP1. ER Stress & Unfolded Protein Response: AMFR, ATF4, ATF6, BAX, DDIT3, DERL1, EDEM1, EDEM3, EIF2AK3, ERN2, ERO1L, ERO1LB, FBXO6, GADD45A, HERPUD1, HTRA2, HTRA4, MBTPS1, MBTPS2, NPLOC4, NUCB1, OS9, PFDN5, SEC62, SEL1L, SELS, SERP1, SYVN1, UBE2G2, UBE2J2, UBXN4, VCP, XBP1. Cytochrome P450s & Phase I Drug Metabolism: CYP1A1, CYP1A2, CYP2B6, CYP2C19, CYP2C9, CYP2D6, CYP2E1, CYP3A4, ESD, FMO2, FMO3, FMO4, FMO5, MAOA, MAOB. Steatosis: ACACA, ADK, ALDH2, AQP4, CD36, COMT, CYP2E1, CYP7B1, DNM1, ENO1, FAS, FASN, GPD1, HAAO, HADHB, KHK, LMNA, LPL, LY6D, MAPK8 (JNK1), MTTP, PCCA, PNPLA3, PPARA, RETN, SCD, SREBF1, SYT1, TFF3, VCP. Cholestasis: ABCB1, ABCB4, ABCC1 (MRP1), ABCC2 (MRP2), ABCC3 (MRP3), APOE, ATP8B1, CYP3A4, CYP7A1, DLAT, ESR1 (ERa), HLA-DRB1, ICAM1, IL10, IL1B, IL2, IL6, JAG1, MPO, NR1H4, NUP210, OSTALPHA, OSTBETA, PDYN, RDX, SLC10A1, TGFB1, TNF. Phospholipidosis: ABCB1 (MDR1), ALDH1A1, ASAH1, ASNS, CES2, CTSB, EPHX1, FABP1, FXC1 (TIMM10B), GSTM4, HPN, INHBE, LSS, MANBA, MLX, MRPS18B, NR0B2, POR, S100A8, SC4MOL, SERPINA3, SLC2A3, SLCO1A2, SMPD1, STBD1, TAGLN, UGT1A1, UGT2A1, UGT2B4, WIPI1. Immunotoxicity: ADH1C, AHR, AHSG, ALB, APOA5, APOF, C3, C9, CASP3, CD19, CD4, CD44, CD80, CD86, CD8A, CTSE, CYP1A1, CYP3A4, CYP3A4, EP300, F2, FABP1, FAS, GPT, GSTA3, HPX, HRG, HSPA5, IFNA1, IFNG, IL10, IL13, IL1A, IL1B, IL2, IL4, IL5, IL6, ITGAX, KLF1, LYZ, LYZ, METAP2, MKI67, NFKB1, NR5A2, PON1, POU3F3, PTGS2 (COX2), PTPRC, SOD1, TNF, TRIM10, UBQLN2. |
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