Objective:To determine fatty acid synthase(FAS)expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma.Methods:FAS expression was determined by immunohistochemistry,re...Objective:To determine fatty acid synthase(FAS)expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma.Methods:FAS expression was determined by immunohistochemistry,re- verse-transcription polymerase chain reaction(RT-PCR)and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma(MM patients)and peripheral blood mononuclear cells(PBMCs)obtained from 12 healthy donors. In parallel,additional analyses were performed on 2 human multiple myeloma cell lines,U266 and RPMI8226.U266 cells were treated with cerulenin at various concentrations(5 to 320μg/ml)for 24 h,and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assays.Apoptosis was evaluated by dual Annexin V/PI (propidium iodide)labeling and flow cytometry(FCM)in U266 cells treated with 20μg/ml cerulenin for 12 h or 24 h.Results:By immunohistochemistry,we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS.Similarly,by RT-PCR,22 of 27 bone marrow samples obtained from MM patients,U266 and RPMI8226 showed FAS expression,whereas PBMC samples from 12 healthy donors did not express detectable level of FAS.FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients,U266 and RPMI8226 cell lines,and no FAS protein expression was detected in PBMC samples from 12 healthy donors.U266 cells were highly sensitive to cerulenin treatment,with a dosage-related effect on metabolic activity,as a measure for cell proliferation.U266 cells treated with 20μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9%and 69.3%Annexin V+/PI ?cells,and late apoptotic and necrotic cells with 3.2%and 17.6%Annexin V+/PI +cells.Conclusion:Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines.Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis,suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.展开更多
Goat milk is widely recognized for its nutritional value.Fatty acid synthase(FAS)is the crucial enzyme of fatty acid de novo synthesis.It plays an important role in the formation of goat milk fat.In this paper,we firs...Goat milk is widely recognized for its nutritional value.Fatty acid synthase(FAS)is the crucial enzyme of fatty acid de novo synthesis.It plays an important role in the formation of goat milk fat.In this paper,we first introduced the molecular regulation process of goat milk fat metabolism based on the structure research of FAS.Secondly,we reviewed some key factors in FAS transcription and post-transcriptional regulation of the goat mammary gland and preliminarily constructed the expression network of the goat mammary gland FAS gene.The purpose of this paper is to systematically introduce the role of FAS in goat milk fat metabolism and to provide a reference for future studies on the mechanism of goat milk fat metabolism.展开更多
基金Project supported by the Medicine and Health Research Fund of Zhejiang Province(No.2007B091)the Office of Education of Zhejiang Province,China(No.20070104)
文摘Objective:To determine fatty acid synthase(FAS)expression in human multiple myeloma and verify its potential as a therapeutic target in multiple myeloma.Methods:FAS expression was determined by immunohistochemistry,re- verse-transcription polymerase chain reaction(RT-PCR)and immunoblot analysis in bone marrow samples obtained from 27 patients with multiple myeloma(MM patients)and peripheral blood mononuclear cells(PBMCs)obtained from 12 healthy donors. In parallel,additional analyses were performed on 2 human multiple myeloma cell lines,U266 and RPMI8226.U266 cells were treated with cerulenin at various concentrations(5 to 320μg/ml)for 24 h,and metabolic activity was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assays.Apoptosis was evaluated by dual Annexin V/PI (propidium iodide)labeling and flow cytometry(FCM)in U266 cells treated with 20μg/ml cerulenin for 12 h or 24 h.Results:By immunohistochemistry,we found that 19 of 27 bone marrow samples obtained from MM patients expressed significantly high levels of FAS.Similarly,by RT-PCR,22 of 27 bone marrow samples obtained from MM patients,U266 and RPMI8226 showed FAS expression,whereas PBMC samples from 12 healthy donors did not express detectable level of FAS.FAS protein expression was confirmed by immunoblot analysis in 16 of 27 bone marrow samples obtained from MM patients,U266 and RPMI8226 cell lines,and no FAS protein expression was detected in PBMC samples from 12 healthy donors.U266 cells were highly sensitive to cerulenin treatment,with a dosage-related effect on metabolic activity,as a measure for cell proliferation.U266 cells treated with 20μg/ml cerulenin for 12 and 24 h also showed early sign of apoptosis with 56.9%and 69.3%Annexin V+/PI ?cells,and late apoptotic and necrotic cells with 3.2%and 17.6%Annexin V+/PI +cells.Conclusion:Increased FAS expression existed in multiple myeloma samples and human myeloma cell lines.Cerulenin greatly inhibited metabolic activity/cell proliferation of U266 cells and induced apoptosis,suggesting that FAS is an effective target for pharmacological therapy in human multiple myeloma.
基金National Natural Sciences Foundation of China (No. 30671503)Youth Science and Technology Innovation Foundation (No. KJ05011)SRT Program (No. 0605A09) of Nanjing Agriculture University.
基金supported by the National Natural Science Foundation of China(Grant Nos.31802035,31872324 and 31601915)the China Postdoctoral Science Foundation(Grant Nos.2017M621841 and 2019T120472).
文摘Goat milk is widely recognized for its nutritional value.Fatty acid synthase(FAS)is the crucial enzyme of fatty acid de novo synthesis.It plays an important role in the formation of goat milk fat.In this paper,we first introduced the molecular regulation process of goat milk fat metabolism based on the structure research of FAS.Secondly,we reviewed some key factors in FAS transcription and post-transcriptional regulation of the goat mammary gland and preliminarily constructed the expression network of the goat mammary gland FAS gene.The purpose of this paper is to systematically introduce the role of FAS in goat milk fat metabolism and to provide a reference for future studies on the mechanism of goat milk fat metabolism.
文摘采用小鼠营养性肥胖模型法,以昆明小鼠为实验动物,设置基础饲料对照组、肥胖模型对照组、共轭亚油酸(conjugated linoleic acid,CLA)高、中、低剂量组,分别连续灌胃6周,考察小鼠体质量、体内脂肪质量、血脂水平、肝脏脂肪酸合成酶(fatty acid synthase,FAS)含量及脏器的变化,研究CLA对小鼠肥胖的抑制作用。结果表明:CLA各剂量组小鼠的Lee’s指数、脂肪系数和血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL-C)水平均显著或极显著低于肥胖模型对照组(P<0.05或P<0.01),高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL-C)水平均极显著高于肥胖模型对照组(P<0.01),各剂量的CLA对小鼠除肝脏以外的其他脏器无显著影响(P>0.05),高剂量(0.15 m L/10 g)CLA可使喂食营养饲料小鼠的各项肥胖指标均处于喂食基础饲料小鼠的水平,表明CLA能有效抑制小鼠肥胖,同时对小鼠生长无毒副作用;CLA可极显著降低小鼠肝脏FAS含量(P<0.01),降低脂肪酸的合成,从而抑制小鼠肥胖。
