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DNA氧化損傷及其在疾病中的角色

2022-01-06
瀏覽次數(shù): 1681

DNA氧化損傷及其在疾病中的角色

BRENDA KNOX | SEPTEMBER 17TH, 2021 | SCIENTIFIC REVIEW

細(xì)胞DNA是一種具有內(nèi)在反應(yīng)性的生物分子,它持續(xù)暴露于有可能造成傷害的環(huán)境中。其中,當(dāng)有氧呼吸和代謝副產(chǎn)物產(chǎn)生的活性氧(ROS)增加時(shí)會(huì)增加DNA損傷的背景值1。在DNA氧化損傷的反應(yīng)中,細(xì)胞激活復(fù)雜的信號(hào)網(wǎng)絡(luò)以促進(jìn)DNA修復(fù)和生存或觸發(fā)細(xì)胞死亡2。然而,當(dāng)這些機(jī)制失效時(shí),基因組的不穩(wěn)定性會(huì)導(dǎo)致疾病的發(fā)生。了解DNA氧化損傷的病理作用對(duì)于開發(fā)癌癥、阿爾茨海默病和糖尿病等疾病的有效療法至關(guān)重要。


DNA損傷的種類

DNA損傷大致可分為外源性因素引起的損傷和內(nèi)源性因素引起的損傷。外源性DNA損傷劑包括紫外線輻射,會(huì)導(dǎo)致相鄰嘧啶之間形成共價(jià)鍵,產(chǎn)生堿基損傷和單鏈斷裂的電離輻射(IR);煙草煙霧中的化學(xué)物質(zhì)可以轉(zhuǎn)化為烷化劑,從而導(dǎo)致堿基之間的錯(cuò)配。內(nèi)源性DNA損傷的原因包括堿基替換或單堿基插入等復(fù)制錯(cuò)誤,自發(fā)性地堿基脫氨基作用會(huì)導(dǎo)致堿基替換。另外氧化應(yīng)激細(xì)胞中自然存在的ROS通過幾種不同的機(jī)制破壞DNA1。


DNA是如何被氧化應(yīng)激損傷的?

在正常情況下,ROS對(duì)細(xì)胞的生長和存活至關(guān)重要。例如,通過與關(guān)鍵信號(hào)分子相互作用,ROS驅(qū)動(dòng)增殖、凋亡和鐵穩(wěn)態(tài)等過程,而巨噬細(xì)胞和中性粒細(xì)胞釋放ROS是抵御入侵病原體的重要防御機(jī)制3,4。然而,在氧化應(yīng)激(ROS產(chǎn)生和機(jī)體抗氧化防御之間的不平衡)條件下,過量的ROS水平已被證明會(huì)導(dǎo)致大約100種不同的氧化堿基損傷和2-脫氧核糖修飾1。在最廣泛研究的活性氧類型中,也就是超氧自由基(?O2?)、過氧化氫(H2O2)和羥基自由基(?OH),到目前為止,羥基自由基是最活潑的。在H2O2Fe2+反應(yīng)過程中產(chǎn)生的羥基自由基,通過加入DNA堿基的雙鍵,從甲基和2`-脫氧核糖糖的C-H鍵中提取氫原子,從而引起DNA損傷5


DNA氧化損傷會(huì)引起哪些疾病?

DNA氧化損傷與多種疾病有關(guān),誘發(fā)并參與到癌癥發(fā)生的過程5,6。值得注意的是,8-羥基-2 '-脫氧鳥嘌呤(8-OHdG)是一種主要的氧化損傷,它被用作氧化應(yīng)激和癌癥的生物標(biāo)記物,并經(jīng)常用于評(píng)估患者暴露于致癌物質(zhì)(如煙草煙霧、石棉纖維或重金屬)后的DNA損傷程度7。與氧化DNA損傷相關(guān)的其他疾病包括神經(jīng)退行性疾病,如阿爾茨海默病和帕金森??;自身免疫性疾病,如類風(fēng)濕性關(guān)節(jié)炎和系統(tǒng)性紅斑狼瘡(SLE);還有糖尿病,心血管疾病和囊性纖維化。


更好地理解DNA氧化損傷

StressMarq Biosciences為我們提供了多種用于研究DNA氧化損傷及其在疾病發(fā)病機(jī)制中的作用的科研試劑。其中包括Anti-DNA/RNA Damage Antibody [15A3] (SMC-155),該抗體經(jīng)多種應(yīng)用驗(yàn)證,以及DNA Damage (8-OHdG) ELISA試劑盒(SKT-120),用于比色檢測血漿或尿液等樣本材料中的8-OHdG生物標(biāo)志物。

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訪問Stressmarq網(wǎng)站,使用我們的圖表來探索與氧化應(yīng)激相關(guān)的疾病,并查看我們所有研究氧化應(yīng)激的產(chǎn)品列表。

DNA氧化損傷及其在疾病中的角色


IHC analysis using Mouse Anti-DNA Damage Monoclonal Antibody, Clone 15A3 (SMC-155). Tissue: inflamed colon. Species: Mouse.


DNA氧化損傷及其在疾病中的角色

Typical Standard Curve for the DNA Damage (8-OHdG) ELISA kit (SKT-120). Competitive ELISA format, assay range: 0.94 – 60 ng/ml.



References

1.?Mechanisms of DNA damage, repair and mutagenesis, Chatterjee N and Walker GC, Environ Mol Mutagen. 2017 Jun;58(5):235-263

2.?DNA damage and the balance between survival and death in cancer biology, Roos WP?et al, Nat Rev Cancer. 2016 16, 20–33

3.?Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling, Ray PD?et al, Cell Signal. 2012 May;24(5):981-90

4.?Mitochondrial reactive oxygen species as major effectors of antimicrobial immunity, Shekhova E, PLoS Pathog 2020 16(5)

5.?Oxidative DNA damage: mechanisms, mutation, and disease, Cooke MS?et al, FASEB J. 2003 Jul;17(10):1195-214

6.?Oxidative Stress and Cancer, Klaunig JE, Curr Pharm Des. 2018;24(40):4771-4778

7.?8-hydroxy-2′ -deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis, Valavanidis A?et al, J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2009 Apr;27(2):120-39

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產(chǎn)品名稱HSP70 ELISA Kit (High-Sensitivity)高靈敏熱休克70蛋白檢測試劑盒
產(chǎn)品描述High-Sensitivity Colorimetric detection of HSP70
反應(yīng)種屬Dog, Human, Monkey, Mouse, Rat 犬,人,猴,小鼠,大鼠
樣本類型Cell lysates, Plasma, Serum, Tissue細(xì)胞裂解液,血清,血漿,組織
檢測方法Colorimetric Assay 比色法
試劑盒類型Sandwich ELISA (Enzyme-linked Immunosorbent Assay) 夾心法
靈敏度0.038 ng/ml
檢測范圍0.42 - 27 ng/ml
孵育時(shí)間30 minutes??30分鐘
檢測的樣本數(shù)40 samples in duplicate??40個(gè)樣本復(fù)孔檢測

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生物體受到外界不利或者有害因素刺激時(shí),會(huì)發(fā)生快速短暫細(xì)胞代謝調(diào)節(jié),此期間細(xì)胞內(nèi)一些正常的基因表達(dá)會(huì)收到抑制,而一組特殊基因則被激活,并表達(dá)增強(qiáng),這類蛋白被稱為熱休克蛋白(heat shock protein,HSP)熱休克蛋白70(heat shock protein 70, Hsp70)是熱休克蛋白家族研究最為深入的蛋白。Stressmarq公司不僅可以提供多種熱休克蛋白70(heat shock protein 70, Hsp70)相關(guān)抗體,也有熱休克蛋白70(HSP70)檢測試劑盒。無論是抗體還是試劑盒,均有大量文獻(xiàn)引用。

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文獻(xiàn)引用

Effects of heated hydrotherapy on muscle HSP70 and glucose metabolism in old and young vervet monkeys.

Kavanagh, K., Davis, A.T., Jenkins, K.A. and Flynn, D.M. (2016) Cell Stress Chaperones. 21(4):717-25.

PubMed ID:?27188431?Reactivity?Monkey?Applications:?Plasma

Elevation of serum heat-shock protein levels in amyotrophic lateral sclerosis.

Miyazaki, D. et al. (2016) Neurol Sci. 37(8):1277-81.

PubMed ID:?27112486?Reactivity?Human?Applications:?Serum

The Brewed Rice Vinegar Kurozu Increases HSPA1A Expression and Ameliorates Cognitive Dysfunction in Aged P8 Mice.

Kanouchi, H. et al. (2016) PLoS ONE. 11(3):e0150796.

PubMed ID:?26943920?Reactivity?Mouse?Applications:?Brain homogenates

Muscle Heat Shock Protein 70 Predicts Insulin Resistance With Aging.

Chichester, L., Wylie, A.T., Craft, S., and Kavanagh, K. (2014) J Gerontol A Biol Sci Med Sci. 70(2):155-62.

PubMed ID:?24532784?Reactivity?African green monkey?Applications:?Plasma and skeletal muscle, and PBMC's

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熱休克蛋白抗體清單

貨號(hào)產(chǎn)品名稱包裝應(yīng)用反應(yīng)物種
SMC-100AHSP70?抗體50 μgWB | IHC | ICC/IF | ELISA | FCM | FACS | IEM | Bl | AMHu | Ms | Rt | Bv | C.el | Dg | Ck | Dr | Cp | GP | Hm | Mk | Pg | Rb | Sh
SMC-104AHSP70/HSC70?抗體50 μgWB | IHC | ICC/IF | IP | FCM | IEMHu | Ms | Rt | Bv | C.el | Bg | Dg | Ck | Dr | Fs | GP | Hm | Mk | Pg | Pl | Rb | Sh | Xe
SMC-106AHSP70/HSC70?抗體50 μgWB | ICC/IF | IHC | IPHu | Ms | Rt | Bv | Sh | Dg | Bg | Fs | GP | Pg | Hm | Rb | Ck | Xe | Dr | Ys
SMC-107AHSP90?抗體50 μgWB | IHC | ICC/IF | IP | ELISA | AMHu | Ms | Rt | Rb | Ck | Dg | Fs | Shk | Hm
SMC-108CHSP90 alpha?抗體25 μgWB | IHC | ELISAHu | Ms | Rt
SMC-109AHSP90?復(fù)合體抗體50 μgIP | ICC/IFHu | Ms | Rt | Rb
SMC-110AHSP60?抗體50 μgWB | IHC | IP | ELISA | FCMHu | Ms | Rt | Bv | Dg | Ck | Dr | GP | Hm | Mk | Pg | Rb | Sh | Xe | Pl | Sw
SMC-111AHSP60?抗體50 μgWB | IHC | FCMHu | Ms | Rt | Bv | Dg | Ck | GP | Hm | Mk | Pg | Rb | Pl | Ba | T.sp | Ys | Is | Fs
SMC-112AHSP90?抗體50 μgWB | IHC | AMHu | Ms | Rt | Rb | Ck | Pl | Fu | Is
SMC-113AHSP70?抗體50 μgWB | ICC/IF | ELISAHu | Ms | Rt | Bv | Pg
SMC-114CHSP25/HSP27?抗體25 μgWB | IHC | ICC/IF | IP | FCM | FACSHu | Ms | Rt | Bv | Dg | GP | Hm | Sh
SMC-120DHSP70/HSC70 (植物)抗體100 μgWB | ELISAPl
SMC-135CHSP90 alpha/beta?抗體25 μgWB | IHC | ICC/IF | ELISAHu | Ms | Rt | Ys
SMC-136CHSP90beta?抗體25 μgWB | IHC | ELISAHu | Ms
SMC-137CHSP90?抗體25 μgWB | IHC | IP | ELISA | AMHu | Ms | Rt | Bv | Pg | Rb | Ck
SMC-145CHSP40, Hdj1?抗體25 μgWB | IHC | ICC/IF | IP | ELISAHu | Ms | Rt
SMC-147BHSP90 alpha?抗體200 μgWB | IHC | ICC/IF | IP | ELISAHu | Ms | Rt
SMC-149AHSP90 (total)?抗體50 μgWB | IHC | ICC/IF | IP | ELISAHu | Ms | Rt | Pl
SMC-150CHSP40, YDJ1?抗體25 μgWB | IP | ELISAYs
SMC-151AHSC70 (HSP73)?抗體50 μgWB | IHC | ICC/IF | IP | ELISA | PLA | PBA | AMHu | Ms | Rt
SMC-161AHSP27?抗體50 μgWB | IHC | ICC/IF | IP | ELISAHu
SMC-162CHSP70?抗體25 μgWB | IHC | ICC/IF | IP | AMHu | Ms | Rt | Am | Ck | Fs | Ys | Dr
SMC-163CHSP70?抗體25 μgWB | IHC | ICC/IF | IP | AMHu | Ms | Rt | Am | Ck | Fs | Ys | Dr
SMC-164CHSP70?抗體25 μgWB | IHC | ICC/IF | IP | AMHu | Ms | Rt | Am | Ck | Fs | Ys | Dr | Ba | BS
SMC-166CHSP40, YDJ1?抗體25 μgWB | IP | ELISAYs
SMC-187CHSP22?抗體25 μgWB | IHC | ICC/IF | ELISAHu | Ms | Rt
SMC-203BHSP47?抗體200 μgWB | ICC/IFHu
SMC-230DHSP70?抗體100 μgWB | ICC/IF | ELISADr
SMC-249DHSP70?抗體100 μgWB | ICC/IF | FCM | FACSHu | Ms | Rt | Bv | Pg
SMC-554DHsp90 alpha?抗體100 μgWB | ELISAHu
SPC-100DHSP40?抗體100 μlWB | ICC/IF | IPHu
SPC-102CHSC70 (HSP73)?抗體25 μlWB | IHC | ICC/IF | IP | BlHu | Ms | Rt | Hm
SPC-103CHSP70?抗體25 μlWB | IHC | ICC/IF | IP | ELISAHu | Ms | Rt | Bg | Bv | Dg | Fs | Cp | GP | Hm | Mk | Pg | Sh | Co | Pl | Shk | L. am
SPC-104CHSP90?抗體25 μlWB | IHC | ICC/IF | IP | ELISAHu | Ms | Rt
SPC-105CHSP60?抗體25 μgWB | IHC | IP | ELISAHu | Ms | Rt | Bv | Dg | Ck | Rb | Hm
SPC-106AHSP27?抗體50 μgWB | ICC/IF | FCM | FACS | IHCHu | Ms | Shk | Dg
SPC-177CHSP90beta?抗體25 μlWB | IHC | ICC/IF | IP | ELISAHu | Ms | Rt
SPC-178CHSP70?抗體25 μgWB | ICC/IF | ELISAHu | Ms | Rt
SPC-181CHSP22?抗體25 μlWB | IHC | ICC/IF | IPHu | Ms | Rt
SPC-184CHSP40?抗體25 μgWB | ICC/IFP.fa
SPC-185CHSP60?抗體25 μgWB | ICC/IF | IHCP.fa | Ba | Hu
SPC-186CHSP70?抗體25 μgWB | ICC/IFP.fa
SPC-187CHSP90?抗體25 μgWB | ICC/IF | IPP.fa
SPC-194CHSPB2?抗體25 μgWB | ICC/IFHu | Ms | Rt
SPC-195CHSP110?抗體25 μgWB | IHC | ICC/IFHu | Ms | Rt | Bv | Mk | Hm | Sh | Ys | Shk
SPC-300BHSP40/DNAJ?抗體200 μlWB | AfPAlg | Ba
SPC-301BHSP70/DNAK?抗體200 μlWBAlg
SPC-304BHSP101/ClpB NT (植物)?抗體200 μlWBPl | Ar
SPC-305BHSP101/ClpB CT (植物)?抗體200 μlWBPl | Ar
SPC-306BHSP101/ClpB CT (玉米)?抗體200 μlWBPl
SPC-307DHSP16.6 (藍(lán)藻菌)?抗體100 μlWBBa
SPC-308BHSP17.6 (植物)?抗體200 μlWBPl | Ar
SPC-309BHSP17.7 (植物)?抗體200 μlWBPl | Ar
SPC-310DHSP21 (植物)?抗體100 μlWBPl | Ar
SPC-311DHSP70/HSC70 (pan)?抗體100 μgWBFs | Mm | Pl | Ar | Ba | Fu
SPC-312DHSP70/HSC70 (植物)?抗體100 μlWBPl | Ar | Fs | Mm
SPC-313DHSP70 (魚)?抗體100 μlWBFs | Slm
SPC-314BHSP70 (魚)?抗體200 μgWB | IHC | IPFs | Slm
SPC-315DHSP70B (植物)?抗體100 μlWB | IPAlg | Pl
SPC-316DHSP90 (鮭魚)?抗體100 μlWBHu | Fs | Slm
SPC-317DHSP90C (植物)?抗體100 μlWB | IPAlg
SPC-318DHSP70?抗體100 μgWBCr
SPC-743DHSP70?抗體?(Acetyl Lys77)100 μlWB | ELISA | ICC/IF | IHCHu | Ms | Rt
SPC-744DHSP70?抗體100 μgWB | ELISAHu | Ms | Rt
SPC-745DHSP90 alpha/beta?抗體100 μgWB | ELISAHu | Ms | Rt
SPC-747DTbHsp70?抗體100 μgWBTb
SPC-995DHSP90AB1?抗體?(pTyr484)100 μlWB | AMHu
SPC-1260DHSP27?抗體?(Ser15)100 μlWB | IHCHu
SPC-1261DHSP27?抗體?(Ser78)100 μlWB | IHCHu
SPC-1262DHSP27?抗體?(Ser82)100 μlWB | IHC | ELISAHu
SPC-1263DHSP27?抗體?(pSer15)100 μlWB | IHC | ICC/IFHu | Ms | Rt
SPC-1264DHSP27?抗體?(pSer82)100 μlWB | IHC | ICC/IFHu | Ms | Rt
SPC-1265DHSP27?抗體?(pSer78)100 μlWB | IHC | ICC/IFHu
SPC-1266DHSP90 beta?抗體?(Ser254)100 μlWB | IHC | IP | ICC/IF | ELISAHu | Ms | Rt
SPC-1267DHSP90 beta?抗體?(pSer254)100 μlWB | IHC | ICC/IF | ELISAHu | Ms | Rt

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