Georges Baffet - Academia.edu (original) (raw)
Papers by Georges Baffet
Biochemical and Biophysical Research Communications, Jul 1, 1989
Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cyto... more Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cytochrome oxidase Subunits I, II, and III mitochondrial genes are present in nuclear DNA from various tissues. These mitochondrial-like sequences are also present in rat hepatoma nuclear DNA but with an abnormal organization and a higher copy number than in normal hepatocytes.
Nucleic Acids Research, Nov 25, 1988
Journal of Histochemistry and Cytochemistry, Apr 1, 1986
Oncogenes are a set of genes which have been implicated in carcinogenesis. They are activated for... more Oncogenes are a set of genes which have been implicated in carcinogenesis. They are activated forms of proto-oncogenes which are part of the genetic complement of all normal cells. These genes are highly conserved during evolution suggesting that they play a critical role in some fundamental phenomena in life.
Matrix Biology, Aug 1, 2018
The collagen network is altered in fibrotic diseases associated with extracellular matrix (ECM) b... more The collagen network is altered in fibrotic diseases associated with extracellular matrix (ECM) biosynthesis and remodeling. This mini-review focuses on the quantitative and qualitative modifications of collagens occurring at the molecular and tissue levels in fibrosis. They result from changes in collagen expression, biosynthesis, enzymatic cross-linking and degradation by several protease families. These molecular modifications, which are mostly regulated by TGF-, are associated with altered collagen organization at the tissue level, leading to a fibrotic signature that can be analyzed by Second Harmonic Generation (SHG) microscopy.
HAL (Le Centre pour la Communication Scientifique Directe), Nov 1, 2015
International audienceMeeting abstract: 19th North American Meeting of the International-Society-... more International audienceMeeting abstract: 19th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) / 29th Meeting of the Japanese-Society-for-the-Study-of-Xenobiotics (JSSX
Protides of the biological fluids, 1982
Abstract The purple membrane of Halobacterium halobium was isolated by isopycnic sucrose density ... more Abstract The purple membrane of Halobacterium halobium was isolated by isopycnic sucrose density gradient centrifugation and subjected to the action of different detergents for solubilization. The membrane was soluble in sodium dodecyl sulfate, cetyl trimethyl ammonium bromide, alkyl-N-sulfobetaines, Triton X-100, and octylglucoside, but not in sodium dodecyl-N-sarcosinate, sodium deoxycholate, or Brij 58. Crossed Immunoelectrophoresis in Triton X-100 or octylglucoside showed that purple membrane samples contained two distinct (not cross-reacting) antigens. They were purified by agarose-suspension electrophoresis in veronal buffer (pH 8.6) containing octylglucoside. The slowest migrating antigen was identified as bacteriorhodopsin by sodium dodecyl sulfate-polyacrylamide gradient electrophoresis. In samples containing the fastest migrating antigen, no protein material was detected by this technique. In addition, its quantity relative to bacteriorhodopsin depended on the profile of the gradients used for purple membrane purification and it was possible to deplete the membrane of this antigen with sodium deoxycholate. These results show that bacteriorhodopsin is immunogenic and antigenic and that the additional antigen detected in purple membrane samples is probably a contaminant, the origin and nature of which are to be determined.
Biochimie, Dec 1, 1985
R~sum6-L'extraction de protdines de la membrane du mollicute 01O'coplasme) Spiroplasma citri par ... more R~sum6-L'extraction de protdines de la membrane du mollicute 01O'coplasme) Spiroplasma citri par le N-doddo,I-N,N-dimdthyl-3-anthto-l-propane sulfonate de sodium (SB,2) et par le N-tdtraddcyl-N,N-dimdthyl-3-anthto-l-propane sulfonate de sodium (SBI4) a dtd dtudide au moyen de techniques dlectrophordtiques. Les membranes, prdpardes h partir de celhdes l),sdes par choc osmotique, dtaient ddbarassdes de l'essentiel ties protdines extrinsdques. Les ddtergents zwitterioniques (Zwittergents) SB~2 et SBt4 sont capables d'extraire jusqu~l 35 et 45 %, respectivement, des protdines de ces membranes, Une extraction maxhnale est obtenue dans les deux cas pour une concentration en ddtergent >t 5 Itmoles/mg de protdines membranaires. La spiraline, protdine majoritaire de la membrane de S. citri, est dissoute de fafon extr£mement sdlective et sans perte de l'antigdnicitd, avec un rendement d'environ 90 % dans le cas de SB12 et de prds de I00 % dans le cas de de SB~, pour une concentration en ddtergent >1 0,2 M. Le degrd de sdlectivitd en faveur de la spiraline est plus dlevd dans le cas de SBI2 (puretd = 70 %) que dans le cas de SB~ (puretd ~-50 %). L'extraction par le SB~2 ,~ concentration dlevde constitue une mdthode shnple et rapide de purification partielle de la spiraline. Cet exemple montre que, dans certahts cas, il est possible de moduler la sdlectivitd de l'extraction de prot~ines membranaires en faisant simplement varier la concentration relative en ddtergent. Mots-el~s : Alkyl-N-sulfob~taines / d~tergents / membrane plasmique / spiraline / Spiroplasma cirri. Summary-The extraction of protehts front the ntembrane of the mollicute (mycoplasma) Spiroplasma citri by sodium N-dodeo,I-N,N-dimethyl-3-anthto-l-propane sulfonate (SB~z) and sodium N.tetradecyl-N,N-dimethyl-3-amhto-l-propane sulfonate (SBI4) was studied with electrophoretic methods. The membranes were prepared by osmotic lysis of the cells attd depleted of the bulk of extrhlsic protehts. It was possible to extract up to 35 attd 45 % of membrane protehts with SB~2 attd SBa4, respectively. Maximal yield was obtahted ht both cases with detergent concen
Biofabrication
In recent decades, 3D in vitro cultures of primary human hepatocytes (PHHs) have been increasingl... more In recent decades, 3D in vitro cultures of primary human hepatocytes (PHHs) have been increasingly developed to establish models capable of faithfully mimicking main liver functions. The use of 3D bioprinting, capable of recreating structures composed of cells embedded in matrix with controlled microarchitectures, is an emergent key feature for tissue engineering. In this work, we used an extrusion-based system to print PHH in a methacrylated gelatin (GelMa) matrix. PHH bioprinted in GelMa rapidly organized into polarized hollow spheroids and were viable for at least 28 d of culture. These PHH were highly differentiated with maintenance of liver differentiation genes over time, as demonstrated by transcriptomic analysis and functional approaches. The cells were polarized with localization of apico/canalicular regions, and displayed activities of phase I and II biotransformation enzymes that could be regulated by inducers. Furthermore, the implantation of the bioprinted structures in...
Journal of Hepatology, 2019
Molecular biology & medicine, 1990
Five rat hepatoma cell lines were shown to secrete hepatocyte-stimulating factors (HSFs) capable ... more Five rat hepatoma cell lines were shown to secrete hepatocyte-stimulating factors (HSFs) capable of inducing a characteristic spectrum of acute phase genes. Three of these lines, but not normal rat livers or livers from rats with an experimentally induced acute inflammation, produced interleukin 6 (IL6) mRNA. An anti-rat IL6 serum was prepared against synthetic peptides derived from the rat IL6 cDNA sequence. This antiserum cleared authentic rat IL6 and a fraction of the HSF activities secreted by the hepatoma cell lines. After concentration of culture supernatants from FTO2B hepatoma cells, IL6 was detected with the anti-IL6 serum by immuno-blot analysis. Biosynthesis of IL6 in the HTC line was demonstrated by metabolic labeling and immunoprecipitation. Secretion of HSF activities by hepatoma cells was increased by serum factors. These data suggest that different rat hepatoma lines each secrete different characteristic sets of HSF activities and establish unambiguously that IL6 is ...
Nucleic Acids Research, 1988
Journal of Hepatology, 2005
Background/Aims: In chronic liver injury, quiescent hepatic stellate cells change into proliferat... more Background/Aims: In chronic liver injury, quiescent hepatic stellate cells change into proliferative myofibroblast-like cells, which are a main source of fibrosis. We have recently reported that these cells synthesize ADAM12, a disintegrin and metalloprotease whose expression is up-regulated by TGF-b1 in liver cancers. Here, we studied the role of the serine/threonine p70 S6 kinase (p70 S6K) in regulating TGF-b1-induced ADAM12 expression. Results: The phophatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the mitogen-activated protein kinase inhibitor, UO126, decreased the TGF-b1-dependent ADAM12 expression and prevented the phosphorylation of p70 S6K. In addition, TGF-b1-induced ADAM12 up-regulation was blocked by the Frap/mTOR inhibitor rapamycin, which abrogated the phosphorylation of p70 S6K. In untreated cells, LY294002 but not rapamycin diminished the basal ADAM12 expression related to inhibition of Akt and the glycogen synthase kinase-3 phosphorylation. Conclusions: The data suggest that TGF-b1 induces ADAM12 gene expression through both the PI3K/Frap-mTOR/p70 S6K and MEK/ERK pathways. In addition, activation of the PI3 pathway might be involved in the basal ADAM12 expression in cultured hepatic stellate cells. The involvement of PI3K in ADAM12 expression, similar to that previously observed for collagen I and fibronectin, suggests common pathways for gene up-regulation in hepatic stellate cells that occur during liver fibrogenesis and contribute to tumor progression.
Biology of the Cell, 1988
The acute hepatotoxicity induced by aflatoxin B1 (AFB1) and the potential protective effect of (+... more The acute hepatotoxicity induced by aflatoxin B1 (AFB1) and the potential protective effect of (+)‐cyanidanol‐3 (Catergen®) were evaluated in both human and rat hepatocyted in primary culture. AFB1‐induced acute toxicity was visualized by light microscope observation and quantified by measurement oflactic dehydrogenase activity in the medium. Human hepatocytes were susceptible to AFB1‐induced cytotoxicity but no evident relationship between the concentration of mycotoxin and the extent of cellular damage was established. (+)‐Cyanidanol‐3 was not toxic at concentrations up to 2×10−3M, but no obvious protective effect from AFB1‐induced injury was evidenced in human cells. By contrast, rat hepatocytes responded in a dose‐related manner toAFB1. (+)‐Cyanidanol was toxic at 10−3M, but even at this concentration exerted a strong protective effect against AFB1‐induced cytotoxicity. Such species differences suggest the existence of metabolic differences in both AFB1 and (+)‐cyanidanol‐3 acti...
Biochimie, 1991
-Interleukin 6 (IL-6) is a central alarm hormone of the mammalian body. During acute and chronic ... more -Interleukin 6 (IL-6) is a central alarm hormone of the mammalian body. During acute and chronic inflammations, it induces acute phase plasma protein synthesis by liver hepatocytes, modulates the immune response and participates in the regulation of body temperature (fever). In addition, it is a growth factor for certain tumor cells, such as myeloma cells. The details of the IL-6 signal transduction mechanism are unknown. We have contributed to this problem at 2 levels: (a), we have mapped an IL-6-response element (IL-6-RE) in the 5' flanking region of the ot2-macroglobulin gene (ot2M), a prototype rat liver acute phase gene. This element, CTGGGA, serves as a binding site for nuclear factors that facilitate hormone induced transcription. We have begun to characterize these factors from hepatic cells and demonstrated that they undergo characteristic IL-6-induced changes. Similar factors were also discovered in human Burkitt tumor derived cell lines (B cells). These bound at the IL-6-RE of the rat ot.tM gene and formed indistinguishable protein DNA complexes, as the corresponding hepatic factors. Thus, common elements probably operate in the IL-6 signal transduction cascade in liver cells and B cells; (b), we have cloned the rat liver IL-6 receptor (IL-6-R) and derived its amino acid sequence. It was 53% identical to the human leukocyte IL-6-R and all functional domains were highly conserved. Therefore, the ceil-type specific responses to IL-6 in liver cells and lymphocytes were probably not due to cell-type specific forms of the receptor, but to other so far unknown elements of the signal transduction cascade. Two mRNA species (cDNA clones) for the rat liver IL-6-R were isolated. Both coded for an identical protein and differed in their 3' untranslated regions (3' UTR), due to alternative polyadenylation. The 3' UTR of the longer mRNA species carried sequence elements associated with regulation of mRNA stability and translation efficiency. Upon transfection into hepatic cells and Jurkat cells (leukocytes), the shorter mRNA species selectively functioned in the Jurkat cells and only the longer mRNA species in hepatic cells. IL-6-R mRNA levels were upregulated 4-fold during an acute phase response. The receptor mRNA was inducible by glucocorticoids and under negative regulation by IL-6. IL-6-R mRNA was further inducible in HL60 promyelocytic cells upon induction of granulocytic differentiation.
Biochemical and Biophysical Research Communications, 1989
Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cyto... more Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cytochrome oxidase Subunits I, II, and III mitochondrial genes are present in nuclear DNA from various tissues. These mitochondrial-like sequences are also present in rat hepatoma nuclear DNA but with an abnormal organization and a higher copy number than in normal hepatocytes.
Biochemical and Biophysical Research Communications, Jul 1, 1989
Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cyto... more Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cytochrome oxidase Subunits I, II, and III mitochondrial genes are present in nuclear DNA from various tissues. These mitochondrial-like sequences are also present in rat hepatoma nuclear DNA but with an abnormal organization and a higher copy number than in normal hepatocytes.
Nucleic Acids Research, Nov 25, 1988
Journal of Histochemistry and Cytochemistry, Apr 1, 1986
Oncogenes are a set of genes which have been implicated in carcinogenesis. They are activated for... more Oncogenes are a set of genes which have been implicated in carcinogenesis. They are activated forms of proto-oncogenes which are part of the genetic complement of all normal cells. These genes are highly conserved during evolution suggesting that they play a critical role in some fundamental phenomena in life.
Matrix Biology, Aug 1, 2018
The collagen network is altered in fibrotic diseases associated with extracellular matrix (ECM) b... more The collagen network is altered in fibrotic diseases associated with extracellular matrix (ECM) biosynthesis and remodeling. This mini-review focuses on the quantitative and qualitative modifications of collagens occurring at the molecular and tissue levels in fibrosis. They result from changes in collagen expression, biosynthesis, enzymatic cross-linking and degradation by several protease families. These molecular modifications, which are mostly regulated by TGF-, are associated with altered collagen organization at the tissue level, leading to a fibrotic signature that can be analyzed by Second Harmonic Generation (SHG) microscopy.
HAL (Le Centre pour la Communication Scientifique Directe), Nov 1, 2015
International audienceMeeting abstract: 19th North American Meeting of the International-Society-... more International audienceMeeting abstract: 19th North American Meeting of the International-Society-for-the-Study-of-Xenobiotics (ISSX) / 29th Meeting of the Japanese-Society-for-the-Study-of-Xenobiotics (JSSX
Protides of the biological fluids, 1982
Abstract The purple membrane of Halobacterium halobium was isolated by isopycnic sucrose density ... more Abstract The purple membrane of Halobacterium halobium was isolated by isopycnic sucrose density gradient centrifugation and subjected to the action of different detergents for solubilization. The membrane was soluble in sodium dodecyl sulfate, cetyl trimethyl ammonium bromide, alkyl-N-sulfobetaines, Triton X-100, and octylglucoside, but not in sodium dodecyl-N-sarcosinate, sodium deoxycholate, or Brij 58. Crossed Immunoelectrophoresis in Triton X-100 or octylglucoside showed that purple membrane samples contained two distinct (not cross-reacting) antigens. They were purified by agarose-suspension electrophoresis in veronal buffer (pH 8.6) containing octylglucoside. The slowest migrating antigen was identified as bacteriorhodopsin by sodium dodecyl sulfate-polyacrylamide gradient electrophoresis. In samples containing the fastest migrating antigen, no protein material was detected by this technique. In addition, its quantity relative to bacteriorhodopsin depended on the profile of the gradients used for purple membrane purification and it was possible to deplete the membrane of this antigen with sodium deoxycholate. These results show that bacteriorhodopsin is immunogenic and antigenic and that the additional antigen detected in purple membrane samples is probably a contaminant, the origin and nature of which are to be determined.
Biochimie, Dec 1, 1985
R~sum6-L'extraction de protdines de la membrane du mollicute 01O'coplasme) Spiroplasma citri par ... more R~sum6-L'extraction de protdines de la membrane du mollicute 01O'coplasme) Spiroplasma citri par le N-doddo,I-N,N-dimdthyl-3-anthto-l-propane sulfonate de sodium (SB,2) et par le N-tdtraddcyl-N,N-dimdthyl-3-anthto-l-propane sulfonate de sodium (SBI4) a dtd dtudide au moyen de techniques dlectrophordtiques. Les membranes, prdpardes h partir de celhdes l),sdes par choc osmotique, dtaient ddbarassdes de l'essentiel ties protdines extrinsdques. Les ddtergents zwitterioniques (Zwittergents) SB~2 et SBt4 sont capables d'extraire jusqu~l 35 et 45 %, respectivement, des protdines de ces membranes, Une extraction maxhnale est obtenue dans les deux cas pour une concentration en ddtergent >t 5 Itmoles/mg de protdines membranaires. La spiraline, protdine majoritaire de la membrane de S. citri, est dissoute de fafon extr£mement sdlective et sans perte de l'antigdnicitd, avec un rendement d'environ 90 % dans le cas de SB12 et de prds de I00 % dans le cas de de SB~, pour une concentration en ddtergent >1 0,2 M. Le degrd de sdlectivitd en faveur de la spiraline est plus dlevd dans le cas de SBI2 (puretd = 70 %) que dans le cas de SB~ (puretd ~-50 %). L'extraction par le SB~2 ,~ concentration dlevde constitue une mdthode shnple et rapide de purification partielle de la spiraline. Cet exemple montre que, dans certahts cas, il est possible de moduler la sdlectivitd de l'extraction de prot~ines membranaires en faisant simplement varier la concentration relative en ddtergent. Mots-el~s : Alkyl-N-sulfob~taines / d~tergents / membrane plasmique / spiraline / Spiroplasma cirri. Summary-The extraction of protehts front the ntembrane of the mollicute (mycoplasma) Spiroplasma citri by sodium N-dodeo,I-N,N-dimethyl-3-anthto-l-propane sulfonate (SB~z) and sodium N.tetradecyl-N,N-dimethyl-3-amhto-l-propane sulfonate (SBI4) was studied with electrophoretic methods. The membranes were prepared by osmotic lysis of the cells attd depleted of the bulk of extrhlsic protehts. It was possible to extract up to 35 attd 45 % of membrane protehts with SB~2 attd SBa4, respectively. Maximal yield was obtahted ht both cases with detergent concen
Biofabrication
In recent decades, 3D in vitro cultures of primary human hepatocytes (PHHs) have been increasingl... more In recent decades, 3D in vitro cultures of primary human hepatocytes (PHHs) have been increasingly developed to establish models capable of faithfully mimicking main liver functions. The use of 3D bioprinting, capable of recreating structures composed of cells embedded in matrix with controlled microarchitectures, is an emergent key feature for tissue engineering. In this work, we used an extrusion-based system to print PHH in a methacrylated gelatin (GelMa) matrix. PHH bioprinted in GelMa rapidly organized into polarized hollow spheroids and were viable for at least 28 d of culture. These PHH were highly differentiated with maintenance of liver differentiation genes over time, as demonstrated by transcriptomic analysis and functional approaches. The cells were polarized with localization of apico/canalicular regions, and displayed activities of phase I and II biotransformation enzymes that could be regulated by inducers. Furthermore, the implantation of the bioprinted structures in...
Journal of Hepatology, 2019
Molecular biology & medicine, 1990
Five rat hepatoma cell lines were shown to secrete hepatocyte-stimulating factors (HSFs) capable ... more Five rat hepatoma cell lines were shown to secrete hepatocyte-stimulating factors (HSFs) capable of inducing a characteristic spectrum of acute phase genes. Three of these lines, but not normal rat livers or livers from rats with an experimentally induced acute inflammation, produced interleukin 6 (IL6) mRNA. An anti-rat IL6 serum was prepared against synthetic peptides derived from the rat IL6 cDNA sequence. This antiserum cleared authentic rat IL6 and a fraction of the HSF activities secreted by the hepatoma cell lines. After concentration of culture supernatants from FTO2B hepatoma cells, IL6 was detected with the anti-IL6 serum by immuno-blot analysis. Biosynthesis of IL6 in the HTC line was demonstrated by metabolic labeling and immunoprecipitation. Secretion of HSF activities by hepatoma cells was increased by serum factors. These data suggest that different rat hepatoma lines each secrete different characteristic sets of HSF activities and establish unambiguously that IL6 is ...
Nucleic Acids Research, 1988
Journal of Hepatology, 2005
Background/Aims: In chronic liver injury, quiescent hepatic stellate cells change into proliferat... more Background/Aims: In chronic liver injury, quiescent hepatic stellate cells change into proliferative myofibroblast-like cells, which are a main source of fibrosis. We have recently reported that these cells synthesize ADAM12, a disintegrin and metalloprotease whose expression is up-regulated by TGF-b1 in liver cancers. Here, we studied the role of the serine/threonine p70 S6 kinase (p70 S6K) in regulating TGF-b1-induced ADAM12 expression. Results: The phophatidylinositol 3-kinase (PI3K) inhibitor LY294002 and the mitogen-activated protein kinase inhibitor, UO126, decreased the TGF-b1-dependent ADAM12 expression and prevented the phosphorylation of p70 S6K. In addition, TGF-b1-induced ADAM12 up-regulation was blocked by the Frap/mTOR inhibitor rapamycin, which abrogated the phosphorylation of p70 S6K. In untreated cells, LY294002 but not rapamycin diminished the basal ADAM12 expression related to inhibition of Akt and the glycogen synthase kinase-3 phosphorylation. Conclusions: The data suggest that TGF-b1 induces ADAM12 gene expression through both the PI3K/Frap-mTOR/p70 S6K and MEK/ERK pathways. In addition, activation of the PI3 pathway might be involved in the basal ADAM12 expression in cultured hepatic stellate cells. The involvement of PI3K in ADAM12 expression, similar to that previously observed for collagen I and fibronectin, suggests common pathways for gene up-regulation in hepatic stellate cells that occur during liver fibrogenesis and contribute to tumor progression.
Biology of the Cell, 1988
The acute hepatotoxicity induced by aflatoxin B1 (AFB1) and the potential protective effect of (+... more The acute hepatotoxicity induced by aflatoxin B1 (AFB1) and the potential protective effect of (+)‐cyanidanol‐3 (Catergen®) were evaluated in both human and rat hepatocyted in primary culture. AFB1‐induced acute toxicity was visualized by light microscope observation and quantified by measurement oflactic dehydrogenase activity in the medium. Human hepatocytes were susceptible to AFB1‐induced cytotoxicity but no evident relationship between the concentration of mycotoxin and the extent of cellular damage was established. (+)‐Cyanidanol‐3 was not toxic at concentrations up to 2×10−3M, but no obvious protective effect from AFB1‐induced injury was evidenced in human cells. By contrast, rat hepatocytes responded in a dose‐related manner toAFB1. (+)‐Cyanidanol was toxic at 10−3M, but even at this concentration exerted a strong protective effect against AFB1‐induced cytotoxicity. Such species differences suggest the existence of metabolic differences in both AFB1 and (+)‐cyanidanol‐3 acti...
Biochimie, 1991
-Interleukin 6 (IL-6) is a central alarm hormone of the mammalian body. During acute and chronic ... more -Interleukin 6 (IL-6) is a central alarm hormone of the mammalian body. During acute and chronic inflammations, it induces acute phase plasma protein synthesis by liver hepatocytes, modulates the immune response and participates in the regulation of body temperature (fever). In addition, it is a growth factor for certain tumor cells, such as myeloma cells. The details of the IL-6 signal transduction mechanism are unknown. We have contributed to this problem at 2 levels: (a), we have mapped an IL-6-response element (IL-6-RE) in the 5' flanking region of the ot2-macroglobulin gene (ot2M), a prototype rat liver acute phase gene. This element, CTGGGA, serves as a binding site for nuclear factors that facilitate hormone induced transcription. We have begun to characterize these factors from hepatic cells and demonstrated that they undergo characteristic IL-6-induced changes. Similar factors were also discovered in human Burkitt tumor derived cell lines (B cells). These bound at the IL-6-RE of the rat ot.tM gene and formed indistinguishable protein DNA complexes, as the corresponding hepatic factors. Thus, common elements probably operate in the IL-6 signal transduction cascade in liver cells and B cells; (b), we have cloned the rat liver IL-6 receptor (IL-6-R) and derived its amino acid sequence. It was 53% identical to the human leukocyte IL-6-R and all functional domains were highly conserved. Therefore, the ceil-type specific responses to IL-6 in liver cells and lymphocytes were probably not due to cell-type specific forms of the receptor, but to other so far unknown elements of the signal transduction cascade. Two mRNA species (cDNA clones) for the rat liver IL-6-R were isolated. Both coded for an identical protein and differed in their 3' untranslated regions (3' UTR), due to alternative polyadenylation. The 3' UTR of the longer mRNA species carried sequence elements associated with regulation of mRNA stability and translation efficiency. Upon transfection into hepatic cells and Jurkat cells (leukocytes), the shorter mRNA species selectively functioned in the Jurkat cells and only the longer mRNA species in hepatic cells. IL-6-R mRNA levels were upregulated 4-fold during an acute phase response. The receptor mRNA was inducible by glucocorticoids and under negative regulation by IL-6. IL-6-R mRNA was further inducible in HL60 promyelocytic cells upon induction of granulocytic differentiation.
Biochemical and Biophysical Research Communications, 1989
Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cyto... more Using specific probes we show that sequences homologous to NADH dehydrogenase Subunit 6, and Cytochrome oxidase Subunits I, II, and III mitochondrial genes are present in nuclear DNA from various tissues. These mitochondrial-like sequences are also present in rat hepatoma nuclear DNA but with an abnormal organization and a higher copy number than in normal hepatocytes.