全球肝脏代谢的变化在早期BC致癌作用。a rt - pcr BC-bearing小鼠肝脏的演示UC的RNA表达酶精氨酸酶减少我在21天的癌症进展(n = 5在每组,学生学习任务)。左面板b:血浆谷氨酰胺的百分比标签注入4 t1肿瘤或PBS控制输液的5个小时后。右面板:谷氨酰胺的意思是同位素内容发现的等离子体注入4 t1肿瘤或PBS控制老鼠,5小时输液后,使用IsoCor生成。c .高浓度的天冬氨酸、谷氨酸和延胡索酸酯水平下降,在肝脏(上半部分)和等离子体(下图)BC-bearing小鼠相比WT-PBS注射小鼠的肝脏。加州大学中级水平与气相色谱分析-质谱法(gc - ms)测定,氨基酸分析仪(AAA),和液体色谱-光谱法(质)(气相n = 5, AAA WT n = 5, 4 t1 n = 4, LCMS n = 5,学生学习任务),P值肝脏:Asp = 0.027, Glu = 0.049,嬉笑= 0.045。Pvalues等离子体:Asp = 0.004, Glu = 0.0005。d .火山UC的情节显示减少表达酶场外,ASS1, CPS1 21天第四天相比BC-bearing老鼠。e .主成分分析(PCA)情节表明显著不同的肝细胞基因表达谱BC-bearing老鼠在21天相比,所有其他实验小组。f .没有改变肝脏特异性RNA表达的基因第4天到21。 Normalized RNA counts for APOE (Left) and KTR18 (Right) in hepatocytes in day4 and day 21 showed no difference in RNA levels between the time points. G. Left panel-plasma measurements of AST demonstrate significantly increased levels in BC-bearing mice in comparison to WT-PBS injected mice (n = 5, student T-Test) P = 0.011. Right panel- no significant changes were found for ALT. H. The enzymatic activities of respiratory chain complexes were measured at 37°C by standard spectrophotometric methods as described in the methods and in [51]. Rotenone-sensitive NADH-CoQ-reductase (CI), succinate-cytochrome C- reductase (CII+CIII), and cytochrome coxidase (CIV). The activities were divided by the activity of succinate dehydrogenase, Complex II (SDH), and expressed as activity(micromol/min/mg) ratio (U/U) (WT n = 5, 4T1 n = 4, student T-Test) P = 0.039. I. qPCR of livers from 4T1 BC mice demonstrates a decrease in mtDNA copy number compared to WT-PBS injected mice (n = 4, student T-Test) P = 0.038, 0.012, 0.026 (respectively).J. Left panel-Western blots demonstrating decreased protein expression levels of TFAM in livers of BC-bearing mice compared to WT-PBS injected mice (n = 5, student T-Test). P = 0.0003. Right panel- quantification of TFAM western band intensity. K. RT-PCR of livers from 4T1 BCmice demonstrates a decreased expression of TFAM compared to WT-PBS injected mice (n =5, student T-Test) P <0.0001. L. No differences in the levels of citrate synthase in mitochondria from the livers of BC mice compared to WT-PBS injected mice (WT n = 5, 4T1 n = 4). Credit:癌症的发现(2023)。DOI: 10.1158 / 2159 - 8290. - cd - 22 - 1062