AbMotle小講堂丨SC79：調(diào)控Akt信號通路，在神經(jīng)保護(hù)、代謝平衡與腫瘤研究中的綜合應(yīng)用SC79（AbMole，M5153）是一種小分子化合物，作為Akt蛋白激酶的特異性激活劑ADDINEN.CITEADDINEN.CITE.DATA[1]。SC79與通過促進(jìn)膜轉(zhuǎn)位進(jìn)而激活A(yù)kt的傳統(tǒng)激活劑有所不同，SC79通過與Akt的PH結(jié)構(gòu)域特異性結(jié)合，誘導(dǎo)Akt發(fā)生構(gòu)象變化并抑制Akt向細(xì)胞膜的轉(zhuǎn)運(yùn)，從而在細(xì)胞質(zhì)中增強(qiáng)Akt的磷酸化水平和激酶活性，最終激活A(yù)kt的下游信號通路。在細(xì)胞生物學(xué)領(lǐng)域，SC79被廣泛用于探索Akt信號的功能。例如，在豬胚胎發(fā)育研究中，SC79通過恢復(fù)Akt活性，逆轉(zhuǎn)了NEK2（絲氨酸/蘇氨酸激酶）抑制引發(fā)的DNA損傷和細(xì)胞增殖缺陷，證實(shí)了Akt通路對胚胎發(fā)育的關(guān)鍵調(diào)控作用ADDINEN.CITEADDINEN.CITE.DATA[2]。SC79在細(xì)胞代謝研究中，被發(fā)現(xiàn)可通過激活A(yù)kt/FoxO1通路，拮抗非酯化脂肪酸（NEFA）對細(xì)胞凋亡的誘導(dǎo)，并上調(diào)固醇調(diào)節(jié)元件結(jié)合蛋白（SREBP-1）等代謝相關(guān)基因的表達(dá)ADDINEN.CITE<EndNote><Cite><Author>Lei</Author><Year>2023</Year><RecNum>1411</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>1411</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1763103564">1411</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lei,Z.</author><author>Ali,I.</author><author>Yang,M.</author><author>Yang,C.</author><author>Li,Y.</author><author>Li,L.</author></authors></contributors><auth-address>CollegeofAnimalScienceandTechnology,NanjingAgriculturalUniversity,Nanjing210095,China.</auth-address><titles><title>Non-EsterifiedFattyAcid-InducedApoptosisinBovineGranulosaCellsviaROS-ActivatedPI3K/AKT/FoxO1Pathway</title><secondary-title>Antioxidants(Basel)</secondary-title><alt-title>Antioxidants(Basel,Switzerland)</alt-title></titles><periodical><full-title>Antioxidants(Basel)</full-title><abbr-1>Antioxidants(Basel,Switzerland)</abbr-1></periodical><alt-periodical><full-title>Antioxidants(Basel)</full-title><abbr-1>Antioxidants(Basel,Switzerland)</abbr-1></alt-periodical><volume>12</volume><number>2</number><edition>2023/02/26</edition><keywords><keyword>FoxO1</keyword><keyword>PI3K/AKTsignaling</keyword><keyword>Ros</keyword><keyword>apoptosis</keyword><keyword>bovinegranulosacells</keyword><keyword>non-esterifiedfattyacid</keyword><keyword>steroidogenesis</keyword></keywords><dates><year>2023</year><pub-dates><date>Feb9</date></pub-dates></dates><isbn>2076-3921(Print) 2076-3921</isbn><accession-num>36829992</accession-num><urls></urls><custom2>PMC9952034</custom2><electronic-resource-num>10.3390/antiox12020434</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]。SC79（CASNo.：305834-79-1）在神經(jīng)科學(xué)研究也展現(xiàn)出重要價值：SC79在阿爾茨海默癥小鼠模型中，通過激活A(yù)kt1信號，顯著提升神經(jīng)細(xì)胞的存活率，并改善動物的長期記憶能力ADDINEN.CITEADDINEN.CITE.DATA[4]。SC79在脊髓損傷研究中，可以通過調(diào)控自噬和焦亡等相關(guān)蛋白的表達(dá)，促進(jìn)脊髓組織修復(fù)和功能恢復(fù)ADDINEN.CITEADDINEN.CITE.DATA[5]。SC79在腫瘤機(jī)制研究中，被用于解析腫瘤細(xì)胞中的PI3K/Akt通路參與的調(diào)控網(wǎng)絡(luò)。例如，在骨髓瘤模型中，SC79被證實(shí)可逆轉(zhuǎn)TMED3（跨膜蛋白）缺失導(dǎo)致的Akt磷酸化水平下降，并通過CDCA8（細(xì)胞周期相關(guān)蛋白）參與的信號通路恢復(fù)細(xì)胞增殖能力ADDINEN.CITEADDINEN.CITE.DATA[6]。SC79的應(yīng)用還擴(kuò)展至微生物領(lǐng)域，例如SC79通過Akt/eNOS（內(nèi)皮型一氧化氮合酶）軸誘導(dǎo)一氧化氮（NO）的劑量依賴性生成，這一過程被證實(shí)可抑制細(xì)菌的增殖ADDINEN.CITEADDINEN.CITE.DATA[7]。范例詳解Antioxidants(Basel).2023Feb9;12(2):434.南京農(nóng)業(yè)大學(xué)的科研人員在上述文章中探究了非酯化脂肪酸（NEFA）對牛顆粒細(xì)胞的影響及Akt激動劑SC79的保護(hù)作用。實(shí)驗人員發(fā)現(xiàn)圍產(chǎn)期奶牛常因能量負(fù)平衡（NEB）導(dǎo)致血液中非酯化脂肪酸（NEFA）水平升高，進(jìn)而影響卵巢功能。上述研究揭示，高濃度非酯化脂肪酸（NEFA）通過ROS激活的PI3K/AKT/FoxO1通路誘導(dǎo)牛顆粒細(xì)胞（BGCs）氧化應(yīng)激、凋亡及類固醇激素合成紊亂，而AKT激活劑SC79可通過靶向該通路緩解這些損傷。在上述實(shí)驗中發(fā)揮關(guān)鍵作用的SC79（305834-79-1，AbMole，M5153）由AbMole提供ADDINEN.CITE<EndNote><Cite><Author>Lei</Author><Year>2023</Year><RecNum>1428</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>1428</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1763359812">1428</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lei,Z.</author><author>Ali,I.</author><author>Yang,M.</author><author>Yang,C.</author><author>Li,Y.</author><author>Li,L.</author></authors></contributors><auth-address>CollegeofAnimalScienceandTechnology,NanjingAgriculturalUniversity,Nanjing210095,China.</auth-address><titles><title>Non-EsterifiedFattyAcid-InducedApoptosisinBovineGranulosaCellsviaROS-ActivatedPI3K/AKT/FoxO1Pathway</title><secondary-title>Antioxidants(Basel)</secondary-title><alt-title>Antioxidants(Basel,Switzerland)</alt-title></titles><periodical><full-title>Antioxidants(Basel)</full-title><abbr-1>Antioxidants(Basel,Switzerland)</abbr-1></periodical><alt-periodical><full-title>Antioxidants(Basel)</full-title><abbr-1>Antioxidants(Basel,Switzerland)</abbr-1></alt-periodical><volume>12</volume><number>2</number><edition>2023/02/26</edition><keywords><keyword>FoxO1</keyword><keyword>PI3K/AKTsignaling</keyword><keyword>Ros</keyword><keyword>apoptosis</keyword><keyword>bovinegranulosacells</keyword><keyword>non-esterifiedfattyacid</keyword><keyword>steroidogenesis</keyword></keywords><dates><year>2023</year><pub-dates><date>Feb9</date></pub-dates></dates><isbn>2076-3921(Print) 2076-3921</isbn><accession-num>36829992</accession-num><urls></urls><custom2>PMC9952034</custom2><electronic-resource-num>10.3390/antiox12020434</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3]。AKTactivatorSC79alleviatedNEFA?inducedROSandoxidativestressinBGCsADDINEN.CITE<EndNote><Cite><Author>Lei</Author><Year>2023</Year><RecNum>1428</RecNum><DisplayText><styleface="superscript">[3]</style></DisplayText><record><rec-number>1428</rec-number><foreign-keys><keyapp="EN"db-id="f2td9w00a22awteprfrp9vaup9d9zwa9tdfr"timestamp="1763359812">1428</key></foreign-keys><ref-typename="JournalArticle">17</ref-type><contributors><authors><author>Lei,Z.</author><author>Ali,I.</author><author>Yang,M.</author><author>Yang,C.</author><author>Li,Y.</author><author>Li,L.</author></authors></contributors><auth-address>CollegeofAnimalScienceandTechnology,NanjingAgriculturalUniversity,Nanjing210095,China.</auth-address><titles><title>Non-EsterifiedFattyAcid-InducedApoptosisinBovineGranulosaCellsviaROS-ActivatedPI3K/AKT/FoxO1Pathway</title><secondary-title>Antioxidants(Basel)</secondary-title><alt-title>Antioxidants(Basel,Switzerland)</alt-title></titles><periodical><full-title>Antioxidants(Basel)</full-title><abbr-1>Antioxidants(Basel,Switzerland)</abbr-1></periodical><alt-periodical><full-title>Antioxidants(Basel)</full-title><abbr-1>Antioxidants(Basel,Switzerland)</abbr-1></alt-periodical><volume>12</volume><number>2</number><edition>2023/02/26</edition><keywords><keyword>FoxO1</keyword><keyword>PI3K/AKTsignaling</keyword><keyword>Ros</keyword><keyword>apoptosis</keyword><keyword>bovinegranulosacells</keyword><keyword>non-esterifiedfattyacid</keyword><keyword>steroidogenesis</keyword></keywords><dates><year>2023</year><pub-dates><date>Feb9</date></pub-dates></dates><isbn>2076-3921(Print) 2076-3921</isbn><accession-num>36829992</accession-num><urls></urls><custom2>PMC9952034</custom2><electronic-resource-num>10.3390/antiox12020434</electronic-resource-num><remote-database-provider>NLM</remote-database-provider><language>eng</language></record></Cite></EndNote>[3].參考文獻(xiàn)及鳴謝ADDINEN.REFLIST[1]E.Mavrogonatou,M.Angelopoulou,S.V.Rizou,etal.,ActivationoftheJNKs/ATM-p53axisisindispensableforthecytoprotectionofdermalfibroblastsexposedtoUVBradiation,Celldeath&disease13(7)(2022)647.[2]S.B.Jeon,H.G.Kang,M.J.Kim,etal.,NEK2supportsporcineembryonicdevelopmentbymodulatingtheAKTsignalingpathway,Lifesciences372(2025)123640.[3]Z.Lei,I.Ali,M.Yang,etal.,Non-EsterifiedFattyAcid-InducedApoptosisinBovineGranulosaCellsviaROS-ActivatedPI3K/AKT/FoxO1Pathway