Changes In Expression Of Various Genes Research Articles

A concise in vitro model for evaluating interactions between macrophage and skeletal muscle cells during muscle regeneration.

Skeletal muscle has a highly regenerative capacity, but the detailed process is not fully understood. Several in vitro skeletal muscle regeneration models have been developed to elucidate this, all of which rely on specialized culture conditions that limit the accessibility and their application to many general experiments. Here, we established a concise in vitro skeletal muscle regeneration model using mouse primary cells. This model allows evaluation of skeletal muscle regeneration in two-dimensional culture system similar to a typical cell culture, showing a macrophage-dependent regenerative capacity, which is an important process in skeletal muscle regeneration. Based on the concept that this model could assess the contribution of macrophages of various phenotypes to skeletal muscle regeneration, we evaluated the effect of endotoxin pre-stimulation for inducing various changes in gene expression on macrophages and found that the contribution to skeletal muscle regeneration was significantly reduced. The gene expression patterns differed from those of naive macrophages, especially immediately after skeletal muscle injury, suggesting that the difference in responsiveness contributed to the difference in regenerative efficiency. Our findings provide a concise in vitro model that enables the evaluation of the contribution of individual cell types, such as macrophages and muscle stem cells, on skeletal muscle regeneration.

Angiotensin 1\u20137 modulates molecular and cellular processes central to the pathogenesis of prostate cancer

Angiotensin 1–7 (Ang1–7) is an endogenous bioactive component of the renin-angiotensin system (RAS). In addition to its cardiovascular properties, its anti-proliferative and anti-angiogenic traits are believed to play important roles in carcinogenesis. The present study examines the influence of Ang1–7 on processes associated with development and progression of prostate cancer cells. Our findings indicate that while Ang1–7 (1 nM; 48 h) can effectively reduce cell proliferation in DU-145, it can induce a significant decrease in the expression of MKI67 in LNCaP. In both cell lines we also observed a reduction in colony size in soft agar assay. A various changes in gene expression were noted after exposure to Ang1–7: those of anti- and pro-apoptotic agents and the NF-kB family of transcription factors, as well as mesenchymal cell markers and vascular endothelial growth factor A (VEGFA). In addition, Ang1–7 was found to modulate cell adhesion and matrix metallopeptidase (MMP) activity. Changes were also observed in the levels of angiotensin receptors and sex steroid hormone receptors. Ang1–7 reduced the levels of estrogen receptor alpha gene (ESR1) and increased the expression of estrogen receptor beta gene (ESR2) in all prostate cancer cells; it also up-regulated androgen receptor (AR) expression in androgen-sensitive cells but contradictory effect was observed in androgen- irresponsive cell lines. In summary, the results confirm the existence of complex network between the various elements of the local RAS and the molecular and cellular mechanisms of prostate cancerogenesis. The response of cancer cells to Ang1–7 appears to vary dependently on the dose and time of incubation as well as the aggressiveness and the hormonal status of cells.

Regulation of cAMP and GSK3 signaling pathways contributes to the neuronal conversion of glioma.

Glioma is the most malignant type of primary central nervous system tumors, and has an extremely poor prognosis. One potential therapeutic approach is to induce the terminal differentiation of glioma through the forced expression of pro-neural factors. Our goal is to show the proof of concept of the neuronal conversion of C6 glioma through the combined action of small molecules. We investigated the various changes in gene expression, cell-specific marker expression, signaling pathways, physiological characteristics, and morphology in glioma after combination treatment with two small molecules (CHIR99021, a glycogen synthase kinase 3 [GSK3] inhibitor and forskolin, a cyclic adenosine monophosphate [cAMP] activator). Here, we show that the combined action of CHIR99021 and forskolin converted malignant glioma into fully differentiated neurons with no malignant characteristics; inhibited the proliferation of malignant glioma; and significantly down-regulated gene ontology and gene expression profiles related to cell division, gliogenesis, and angiogenesis in small molecule–induced neurons. In vivo, the combined action of CHIR99021 and forskolin markedly delayed neurological deficits and significantly reduced the tumor volume. We suggest that reprogramming technology may be a potential treatment strategy replacing the therapeutic paradigm of traditional treatment of malignant glioma, and a combination molecule comprising a GSK3 inhibitor and a cAMP inducer could be the next generation of anticancer drugs.

Low-shear-modeled microgravity-grown Penicillium chrysogenum-mediated biosynthesis of silver nanoparticles with enhanced antimicrobial activity and its anticancer effect in human liver cancer and fibroblast cells.

Gravitational force and shear forces induce various changes in gene expression and metabolite production of microorganisms. Previous reports have shown that there are differences in the expression of different sets of proteins and enzymes under microgravity conditions compared to normal gravity. The aim of this study is to utilize culture filtrates of Penicillium chrysogenum grown under microgravity and normal conditions to synthesize silver nanoparticles and to examine whether there is any difference between their physiochemical and biological function. Synthesized nanoparticles were characterized using UV-Vis spectroscopy, FTIR, XRD, and TEM. Biological functional studies such as antimicrobial activity, cytotoxic studies, and anticancer activity were carried out. Antimicrobial activity was tested using antibiotic susceptibility testing by Kirby-Bauer method and cytotoxicity tests were carried out using 3T3-L1 normal fibroblasts cells and Hep-G2 cancer cell lines. Interestingly, our results indicated that microgravity-synthesized silver nanoparticles possess enhanced antibacterial activity and cytotoxic effect against cancer cells compared to normal gravity-synthesized silver nanoparticle. This work highlighted the importance of gravitational vector on the fungal enzyme profiles and their role in silver nanoparticle synthesis with enhanced biological activity.

Identification of genes induced by benzophenone-2 in human thyroid follicular FTC-238 cells

Benzophenone-2 (BP2) is used as a UV screen in many cosmetics of daily use, which regularly come in contact with the human skin. It is well known that BP2 is an endocrine-disrupting chemical (EDC) that disrupts the thyroid hormone axis via the inhibition of thyroid peroxidase. However, the molecular mechanism of BP2-induced cellular toxicity remains unclear. We undertook a genome-wide analysis of transcriptional responses of human thyroid follicular carcinoma FTC-238 cells to non-toxic doses of BP2 (1 and 50 μM). Whole human genome microarrays detected a total of 4,495 genes that exhibited altered expression after exposure to both non-toxic doses of BP2 compared with a vehicle control, DMSO. We found that 534 and 4,142 genes showed different expression levels following treatment with the low and high nontoxic doses of BP2, respectively. Thus, low doses of BP2 can induce various changes in gene expression. The BP2 responsive genes were involved in glycolysis, translation, apoptosis, cell proliferation, generation of precursor metabolites and energy, and microtubulebased processes. Commonly expressed genes by 1 μM and 50 μM of BP2 treatments were associated with glycolysis components, including GAPDH, ENO1, PGK1, TROVE2, LDHA, ALDOA, and PKM2. The downregulated GAPDH, and ENO1 are typical glycolytic transcripts in glycolysis. The disruption of glycolysis including nutrients-replete conditions influences on cell cycle arrest or apoptosis. The possible roles of the responsive genes and their related pathways in BP2-induced cellular responses are discussed. This study helps to understand how cells respond to BP2 exposure via transcriptional regulation.

Identification of early responsive genes in human amnion epithelial FL cells induced by N-methyl- N′-nitro- N-nitrosoguanidine using oligonucleotide microarray and quantitative real-time RT-PCR approaches

The alkylating agent N-methyl- N′-nitro- N-nitrosoguanidine (MNNG) induces cellular DNA damage and other comprehensive alterations that lead to chromosomal aberrations, mutations, tumor initiation, and cell death. However, the molecular mechanism of MNNG-induced cellular stress remains unclear. We undertook a genome-wide analysis of early transcriptional responses of human FL amnion epithelial cells to three relatively low doses of MNNG (0.2, 1.0, and 10.0 μM). Using Affymetrix GeneChip HG-U133 Set oligonucleotide microarrays, a total of 281 genes were found to change their expression after exposure to all three doses of MNNG compared with the vehicle control, DMSO. Of these, 70, 112, and 146 genes showed different expression levels following treatment with low, medium, and high-dose MNNG, respectively. A subset of these genes were selected for further confirmation using quantitative real-time RT-PCR with ABI TaqMan ® low-density arrays, and the differential expression of 33 genes was validated. The results demonstrate that low doses of MNNG can induce various changes in gene expression at an early stage of exposure. The responsive genes are involved in multiple cellular biological processes including transcription regulation, signal transduction, cell cycle regulation, cytoskeleton organization, protein synthesis, immune responses, and metabolism. The cell cycle progression was down-regulated, in which several genes were validated involved, including the cell cycle regulators ( CDK6, STK6, C ENPA, and CCNF), the transcription factor ID-1, and the calcium signaling molecules ( CAMK2G and NFAT5). The possible roles of the responsive genes and their related pathways in MNNG-induced cellular responses are discussed. This study helps to complete the picture of how cells respond to environmental chemical exposure via transcriptional regulation.

Transcriptome analysis of the secretion stress response of Bacillus subtilis

Transcription profiling of all protein-encoding genes of Bacillus subtilis was carried out under several secretion stress conditions in the exponential growth phase. Cells that secreted AmyQ alpha-amylase at a high level were stressed only moderately: seven genes were induced, most significantly htrA and htrB, encoding quality control proteases, and yqxL, encoding a putative CorA-type Mg(2+) transporter. These three genes were induced more strongly by severe secretion stress (prsA3 mutant secreting AmyQ), suggesting that their expression responds to protein misfolding. In addition, 17 other genes were induced, including the liaIHGFSR (yvqIHGFEC) operon, csaA and ffh, encoding chaperones involved in the pretranslocational phase of secretion, and genes involved in cell wall synthesis/modification. Severe secretion stress caused downregulation of 23 genes, including the prsA paralogue yacD. Analysis of a cssS knockout mutant indicated that the absence of the CssRS two-component system, and consequently the absence of the HtrA and HtrB proteases, caused secretion stress. The results also suggest that the htrA and htrB genes comprise the CssRS regulon. B. subtilis cells respond to secretion/folding stress by various changes in gene expression, which can be seen as an attempt to combat the stress condition.

Gene Expression and the Response to Ischemic Insults in Brain: Studies in a Gerbil Model of Induced Tolerance.

Brief ischemic insults protect against injury following subsequent longer and otherwise damaging periods of ischemia, although such protective effects have usually been quite variable. Selective changes in gene expression are considered good candidates for mediators of the tolerance phenomenon, and the stress protein, hsp72, has received considerable attention in this regard. In recent experiments we have monitored the interval of ischemic depolarization following brief periods of occlusion and have identified depolarization thresholds for tolerance, for injury and for various changes in gene expression. While hsp72 is clearly inducible after moderate insults that do not injure neurons, our results indicate that neuronal protection can be achieved by even milder insults that do not appreciably induce hsp72, but that do induce immediate-early genes of the Fos and Jun families with lower depolarization thresholds. In addition, these studies provide the basis for a reproducible model in which mechanisms of tolerance can be further studied.

In situ Hybridization: Application to the Study of Gene Expression during Experimental Hepatocarcinogenesis and Human Hepatocellular Carcinoma

The possibility of detecting specific mRNA directly within tumor cells offered by the in situ hybridization (ISH) technique has provided a new dimension to the study of experimental and human hepatocarcinogenesis. The combination of ISH and immunocytochemical techniques on the same or adjacent tissue sections provides a more complete picture of the various changes in gene expression. ISH may also detect posttranscriptional abnormalities of gene expression at the cellular level, such as expression of mRNA with no protein translation, or translation with decreased efficiency. Undoubtedly, the development of the ISH technique will open a new area for the understanding of the complex molecular events leading to cancer.

Estrogen receptor can distinguish among various halodeoxyuridine-substituted DNAs

FEBS LettersVolume 98, Issue 2 p. 347-350 Full-length articleFree Access Estrogen receptor can distinguish among various halodeoxyuridine-substituted DNAs John Kallos, John Kallos Research Institute of the Hospital for Joint Diseases, and Medical Center, Mt Sinai School of Medicine, 1919 Madison Avenue, New York, NY 10035, USASearch for more papers by this authorThomas M. Fasy, Thomas M. Fasy Roche Institute of Molecular Biology, Nutley, NJ 07110, USASearch for more papers by this authorVincent P. Hollander, Vincent P. Hollander Research Institute of the Hospital for Joint Diseases, and Medical Center, Mt Sinai School of Medicine, 1919 Madison Avenue, New York, NY 10035, USASearch for more papers by this authorMichael D. Bick, Michael D. Bick Roche Institute of Molecular Biology, Nutley, NJ 07110, USA Present address: San Joaquin Hematology Oncology Medical Group, 2727 Eye Street, Bakersfield, CA 93301, USA Search for more papers by this author John Kallos, John Kallos Research Institute of the Hospital for Joint Diseases, and Medical Center, Mt Sinai School of Medicine, 1919 Madison Avenue, New York, NY 10035, USASearch for more papers by this authorThomas M. Fasy, Thomas M. Fasy Roche Institute of Molecular Biology, Nutley, NJ 07110, USASearch for more papers by this authorVincent P. Hollander, Vincent P. Hollander Research Institute of the Hospital for Joint Diseases, and Medical Center, Mt Sinai School of Medicine, 1919 Madison Avenue, New York, NY 10035, USASearch for more papers by this authorMichael D. Bick, Michael D. Bick Roche Institute of Molecular Biology, Nutley, NJ 07110, USA Present address: San Joaquin Hematology Oncology Medical Group, 2727 Eye Street, Bakersfield, CA 93301, USA Search for more papers by this author First published: February 15, 1979 https://doi.org/10.1016/0014-5793(79)80214-8Citations: 4 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References 1 E.V. Jensen, E.R. DeSombre, Ann. Rev. Biochem., 41, (1972), 203– 230. 2 K.R. Yamamoto, B.M. Alberts, Ann. Rev. Biochem., 45, (1976), 721– 746. 3 J. Gorski, F.A. Gannon, Ann. Rev. Physiol., 38, (1976), 425– 450. 4 R.J.B. King, W.I.P. Mainwaring, Steroid—Cell Interactions (1974), University Park Press Baltimore, MD 5 R.E. Buller, B.W. O'Malley, Biochem. Pharmacol., 25, (1976), 1– 12. 6 J.J. Monahan, S.E. Harris, B.W. O'Malley, J. Biol. Chem., 251, (1976), 3738– 3748. 7 J. Kallos, V.P. Hollander, Nature, 272, (1978), 177– 179. 8 J. Kallos, T.M. Fasy, V.P. Hollander, M.D. Bick, Proc. Natl. Acad. Sci. USA, 75, (1978), 4896– 4900. 9 B.R. Cullen, M.D. Bick, Biochim. Biophys. Acta, 517, (1978), 158– 168. 10 W.J. Rutter, R.L. Pictet, P.W. Morris, Ann. Rev. Biochem., 42, (1973), 601– 646. 11 S. Lin, A.D. Riggs, Proc. Natl. Acad. Sci. USA, 69, (1972), 2574– 2576. 12 S. Lin, A.D. Riggs, Biochim. Biophys. Acta, 432, (1976), 185– 191. 13 M. Bick, R. Davidson, Proc. Natl. Acad. Sci. USA, 71, (1974), 2082– 2086. 14 D. Luk, M. Bick, Anal. Biochem., 77, (1977), 346– 349. 15 S. Lin, A.D. Riggs, J. Mol. Biol., 72, (1972), 671– 690. 16 S. Lin, D. Lin, A. Riggs, Nucl. Acid Res., 3, (1976), 2183– 2191. 17 Fasy, T. M. and Bick, M. D. (1978) unpublished data. 18 Fasy, T. M., Kallos, J. and Bick, M. D. (1979) submitted. 19 W. Müller, D.M. Crothers, J. Mol. Biol., 35, (1968), 251– 290. 20 H. Sobell, S.C. Jain, J. Mol. Biol., 68, (1972), 21– 34. 21 C.D. Bugg, H. Sternglanz, E. Bergmann B. Pullman Molecular and Quantum Pharmacology (1974), D. Reidel Publ Dordrecht-Holland 473– 500. 22 H.M. Sobell, C. Tsai, S.C. Jain, S.G. Gilbert, J. Mol. Biol., 114, (1977), 333– 365. 23 S. Lin, A.D. Riggs, Cell, 4, (1975), 107– 111. 24 A.P. Butler, A. Revzin, P.H. Von Hippel, Biochemistry, 16, (1977), 4757– 4768. 25 K.L. Berkner, W.R. Folk, J. Biol. Chem., 252, (1977), 3185– 3193. 26 S.J. Stahl, M.J. Chamberlin, J. Biol. Chem., 253, (1978), 4951– 4959. Citing Literature Volume98, Issue2February 15, 1979Pages 347-350 ReferencesRelatedInformation