Ria discussed above. We speculate that the over-expression of lysosome-related genes could reflect increased numbers

Ria discussed above. We speculate that the over-expression of lysosome-related genes could reflect increased numbers of lysosomes and/or simply the increased functional activity of existing lysosomes.A549 0 xenograft transcriptomes indicate decreased cell proliferation and glycolysis Mitosis (21 transcripts) and spindle JNJ-26481585 web organization and biogenesis (9 transcripts) were two major functional categories showing enrichment for down-regulated transcripts in A549 0 xenografts (Additional File 8B). This would be expected given the lower proliferation rate of the A549 0 cells relative to their parental counterparts PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/29045898 (Fig. 1A). The enrichment in the actin binding (21 transcripts) and cytoskeleton protein binding (27 transcripts) categories could also reflect differences in growth rates. Alternatively, they could relate to altered mitochondrial morphology, as discussed in our analysis of cultured 0 cells.The transcriptional induction of tRNA synthetases was previously highlighted in the analysis of cultured 0 and parental lymphoblasts [44]. Recently, there is increased evidence that tRNA synthetases have functions additional to joining specific amino acids to their cognate tRNAs. These include the regulation of angiogenesis and inflammation [54,55]. The over-expression of MHC Class I peptides is consistent with a report that MHC I is over-expressed in fibroblasts from patients with mtDNA defects as well as in cultured osteosarcoma 0 cells relative to their parental counterparts [56]. In that study, IFN- treatment enhanced MHC1 over-expression in cultured osteosarcoma 0 cells. Thus, the over-expression of interferon gamma receptor 1 (INFGR1) we observed in A549 0 xenografts (1.8-fold,Surprisingly, A549 0 xenografts showed decreased expression in the glycolysis category (nine transcripts). This would appear to be counter-intuitive given the fact that these xenografts do not express mtDNA-derived transcripts (Additional File 1) or MT-COX2 protein (Fig. 3B) and thus should have severely impaired oxidative phosphorylation. Indeed, the 4.7-fold increased abundance of PCK2 in A549 0cells could indicate higher levels of gluconeogenesis, consistent with prior reports in mtDNAdepleted A549 [12], 206B 0osteosarcoma [58], and ARPE19 0 retinal pigment epithelial [58] cultured cells. Apart from the aforementioned lower growth rate of 0 xenografts, this probably reflects the general reduced abundance of HIF-regulated transcripts (GAPDH, PKM2, ENO2, LDHA, EGLN1, SLC2A1, TF, P4HA1, IGF2, CA9, HIG2, ADM, and EGLN3) as compared to the parental A549 xenografts (Additional File 6). This occurs despite the fact that HIF-1 is over-expressed (2.6-fold, P = 1.6 ?10-4) along with two other well-established HIF targets (HK1 and BHLHB3). As discussed earlier, this is consistentPage 9 of(page number not for citation purposes)BMC Genomics 2008, 9:http://www.biomedcentral.com/1471-2164/9/Relative level of HIF-1 protein6 53.2 4.9 3.3.MTC02 PGK1 DDIT31.2.GLUT1 HSP60 HSC1A549 A549 Co(II) AA549 0 A549 A549 0 Co(II) hypoxia hypoxiaFigure 3HIF-1 and HIF-1 target proteins in A549 and A549 0 cells Levels of Levels of HIF-1 and HIF-1 target proteins in A549 and A549 0 cells. Plateau phase cultures were treated with control vehicle (mannitol), cobalt acetate (cobalt, 100 M), or hypoxia (1.5 oxygen atmosphere). (A) Levels of HIF-1 protein relative to control vehicle after 4 hours treatment as measured by ELISA. Effect of incubation under hypoxic conditions or with cobalt acetate is shown.