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| 1 | Liver-specific deletion of mechanistic target of rapamycin does not protect against acetaminophen-induced liver injury in mice显示文摘Background:Acetaminophen(APAP)overdose can cause liver injury and liver failure,which is one of the most common causes of drug-induced liver injury in the United States.Pharmacological activation of autophagy by inhibiting mechanistic target of rapamycin(mTOR)protects against APAP-induced liver injury likely via autophagic removal of APAP-adducts and damaged mitochondria.In the present study,we aimed to investigate the role of genetic ablation of mTOR pathways in mouse liver in APAP-induced liver injury and liver repair/regeneration.Methods:Albumin-Cre(Alb-Cre)mice,mTOR^(f/f) and Raptor^(f/f) mice(C57BL/6J background)were crossbred to produce liver-specific mTOR knockout(L-mTOR KO,Alb Cret/-,mTOR^(f/f))and liver-specific Raptor KO(L-Raptor,Alb Cret/-,Raptor^(f/f))mice.Alb-Cre littermates were used as wild-type(WT)mice.These mice were treated with APAP for various time points for up to 48 h.Liver injury,cell proliferation,autophagy and mTOR activation were determined.Results:We found that genetic deletion of neither Raptor,an important adaptor protein in mTOR complex 1,nor mTOR,in the mouse liver significantly protected against APAP-induced liver injury despite increased hepatic autophagic flux.Genetic deletion of Raptor or mTOR in mouse livers did not affect APAP metabolism and APAP-induced c-Jun N-terminal kinase(JNK)activation,but slightly improved mouse survival likely due to increased hepatocyte proliferation.Conclusions:Our results indicate that genetic ablation of mTOR in mouse livers does not protect against APAP-induced liver injury but may slightly improve liver regeneration and mouse survival after APAP overdose. | Hua Sun Hong-Min Ni Jennifer M.McCracken Jephte Y Akakpo Sam Fulte Tara McKeen Hartmut Jaeschke Hua Wang Wen-Xing Ding | 2021 | Liver Research2021，5，2： | 3 |
| 2 | Immunocytochemical mapping of the phosphatase and tesin homolog(PTEN/MMAC1) tumor suppressor protein in human gliomas显示文摘 | Pedone C | 2000 | Neuro-oncol2000，2，2： | 1 |
| 3 | P53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression显示文摘 | BROCKMEYRR D TULLOUS M W | 1992 | Cancer Res1992，52，： | 1 |
| 4 | Apoptosis suppression by somatic cell transfer of Bcl-2 promotes Sonic hedgehogdependent medulloblastoma formation in mice显示文摘 | McCall TD Pedone CA Fults DW | | 0，，11： | 1 |
| 5 | Chromosome 11P15 deletlons in human malignant astroytomas and primitive neuroectoclmal tumors显示文摘 | Fults D Petronio J Noblett B D | 1992 | Genomics1992，4，3： | 1 |
| 6 | Spontaneous hemorrhage associated with a pilomyxoid astrocytoma 显示文摘 | Gottfried ON Fults DW Townsend JJ | 2003 | J Neurosurg2003，99，2： | 1 |
| 7 | Natural history of arteriovenous malformations of the brain显示文摘 | Fults D | 1984 | Neurosurgery1984，15，5： | 1 |
| 8 | Loss of heterozygosity on chromosome 10 inhuman glioblastoma multiforme 显示文摘 | Fujimoto N Fults DW Thomas GA | 1989 | Genomics1989，4，2： | 1 |
| 9 | Natural history of arteriovenous malformations of the brain:a clinical study显示文摘 | Fults D Kelly DJ | 1984 | Neurosurgery1984，15，： | 1 |
| 10 | Molecular, genetic, and cellular pathogenesis of neurofibromas and surgical implications 显示文摘 | Gottfried ON Viskochil DH Fults DW | 2006 | Neurosurgery2006，58，： | 1 |
| 11 | Sustained release of urease from a poloxamer gel matrix显示文摘 | Fults KA Johnston TP | 1990 | J Parenter Sci Technol1990，44，2： | 1 |
| 12 | P53 mutation and loss of heterozygosity on chromosome 17 and 10 during human astrocytoma progression 显示文摘 | Fults D Brockmeyer D Tullous MW | 1992 | Cancer Res1992，52，3： | 1 |
| 13 | P53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression显示文摘 | Fults D Brockmeyer D Tullous MW | 1992 | Cancer Res1992，52，3： | 1 |
| 14 | P53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression显示文摘 | Fults D Brookmeyer D Tullous MW | 1992 | Cancer Res1992，52，： | 1 |
| 15 | Allelotype of human malignant astrocytoma显示文摘 | Fults D Pedone C A Thomas G A | 1990 | Cancer Res1990，50，18： | 1 |
| 16 | Molecular,genetic,and cellular pathogenesis of neurofibromas and surgicalimplications显示文摘 | Gottfried ON Viskochil DH Fults DW el al | 2006 | Neurosurgery2006，58，1： | 1 |
| 17 | Spontaneous hemorrhage associated with a pilomyxoida astrocytoma:Case report显示文摘 | Gottfried ON Fults DW Townsend JJ | 2003 | J Neuorsurg2003，99，2： | 1 |
| 18 | p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression显示文摘 | Fults D Brockmeyer D Tullous MW | 1992 | Cancer Res1992，52，3： | 1 |
| 19 | p53 mutation and loss of heterozygosity on chromosomes 17 and 10 during human astrocytoma progression显示文摘 | Fult D Brockmeyer D Tullous MW | 1992 | Cancer Res1992，52，3： | 1 |
| 20 | Natural history of arteriovenous malformations of the brain:a clinical study显示文摘 | Fults D Kelly DL Jr | 1984 | Neurosurgery1984，15，： | 1 |
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