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Complex analysis of genes involved in the inflammatory response: interleukin-1-induced differential transcriptome of cultured human hepatoma HepG2 cells.

100%
Koj A., Jura J.
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2003
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vol. 50
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issue 3
573-582
EN
The systemic inflammatory reaction (acute phase response) is induced by many noxious stimuli but in all cases the inflammatory cytokines, such as interleukin-1-beta (IL-1β) and interleukin-6 (IL-6), are involved. Liver cell response to inflammation manifested by a characteristic change in the profile of synthesized plasma proteins (acute phase proteins) has been extensively studied. Here we describe a model system of cultured human hepatoma HepG2 cells stimulated with IL-1β to evaluate the transcriptome induced by this cytokine during 24 h of treatment. By using differential display analysis we found IL-1β-induced upregulation of several genes coding for cellular trafficking/motor proteins, proteins participating in the translation machinery or involved in posttranscription/posttranslation modifications, proteases, proteins involved in cellular metabolism, activity modulators, proteins of the cell cycle machinery and also some new proteins so far functionally not classified.
2
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Regulatory mechanisms of gene expression: complexity with elements of deterministic chaos

81%
Jura J., Węgrzyn P., Jura J., Koj A.
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2006
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vol. 53
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issue 1
1-10
EN
Linear models based on proportionality between variables have been commonly applied in biology and medicine but in many cases they do not describe correctly the complex relationships of living organisms and now are being replaced by nonlinear theories of deterministic chaos. Recent advances in molecular biology and genome sequencing may lead to a simplistic view that all life processes in a cell, or in the whole organism, are strictly and in a linear fashion controlled by genes. In reality, the existing phenotype arises from a complex interaction of the genome and various environmental factors. Regulation of gene expression in the animal organism occurs at the level of epigenetic DNA modification, RNA transcription, mRNA translation, and many additional alterations of nascent proteins. The process of transcription is highly complicated and includes hundreds of transcription factors, enhancers and silencers, as well as various species of low molecular mass RNAs. In addition, alternative splicing or mRNA editing can generate a family of polypeptides from a single gene. Rearrangement of coding DNA sequences during somatic recombination is the source of great variability in the structure of immunoglobulins and some other proteins. The process of rearrangement of immunoglobulin genes, or such phenomena as parental imprinting of some genes, appear to occur in a random fashion. Therefore, it seems that the mechanism of genetic information flow from DNA to mature proteins does not fit the category of linear relationship based on simple reductionism or hard determinism but would be probably better described by nonlinear models, such as deterministic chaos.
3
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Limited GADD45α expression and function in IL-1β toxicity towards insulin-producing cells

71%
Skalniak L., Gurgul-Convey E., Okreglicka K., Skalniak A., Jura J.
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2013
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vol. 60
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issue 4
595-602
EN
Growth arrest and DNA damage-inducible (GADD) 45 proteins are regulators of cell death and survival. The proinflammatory cytokine IL-1β strongly increases the level of the transcript encoding GADD45α in rat insulin-producing INS-1E cells. The activation of Gadd45α gene is clearly dependent on JNK and NF-κB activation and the synthesis of the secondary mediator nitric oxide (NO). Interestingly, the observed twelve-fold increase in the GADD45α-coding transcript level is not followed by increased expression of GADD45α at the protein level. An analysis of IL-1β toxicity in INS-1E cells overexpressing GADD45α revealed no correlation between the GADD45α protein level and the sensitivity to IL-1β toxicity. These findings suggest that the potential engagement of GADD45α in IL-1β toxicity towards beta cells is limited to the effects induced by the basal expression level of this protein.
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