The Experts below are selected from a list of 267 Experts worldwide ranked by ideXlab platform
Philip H. Howe - One of the best experts on this subject based on the ideXlab platform.
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smad3 potentiates transforming growth factor β tgfβ induced apoptosis and expression of the bh3 only protein bim in wehi 231 b lymphocytes
Journal of Biological Chemistry, 2003Co-Authors: Gary M. Wildey, Supriya Patil, Philip H. HoweAbstract:Transforming growth factor-beta (TGFbeta) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance. Here we show that exogenous overexpression of Smad3 potentiates TGFbeta-induced apoptosis and expression of the pro-apoptotic protein Bim in WEHI 231 B lymphocytes. Overexpression of dominant-negative forms of Smad3 abrogate these TGFbeta-induced responses. We also demonstrate that TGFbeta induces Bim protein expression concomitant with its induction of apoptosis in the mouse progenitor B lymphocyte Cell Line, Ba/F3. Enhanced expression of Bim protein induced by TGFbeta is associated with an increased association of Bim with Bcl-2 and a concomitant loss of mitochondrial membrane potential. Furthermore, we find that the anti-apoptotic effect of the pro-survival cytokine CD40 results in the abrogation of TGFbeta-mediated Bim induction. Our data provide the first evidence of Bim expression levels that are increased by the addition of a pro-apoptotic cytokine, TGFbeta, and also suggest that the TGFbeta-specific transcription factor Smad3 plays a role in mediating Bim expression levels and apoptosis.
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Smad3 Potentiates Transforming Growth Factor β (TGFβ)-induced Apoptosis and Expression of the BH3-only Protein Bim in WEHI 231 B Lymphocytes
Journal of Biological Chemistry, 2003Co-Authors: Gary M. Wildey, Supriya Patil, Philip H. HoweAbstract:Abstract Transforming growth factor-β (TGFβ) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance. Here we show that exogenous overexpression of Smad3 potentiates TGFβ-induced apoptosis and expression of the pro-apoptotic protein Bim in WEHI 231 B lymphocytes. Overexpression of dominant-negative forms of Smad3 abrogate these TGFβ-induced responses. We also demonstrate that TGFβ induces Bim protein expression concomitant with its induction of apoptosis in the mouse progenitor B lymphocyte Cell Line, Ba/F3. Enhanced expression of Bim protein induced by TGFβ is associated with an increased association of Bim with Bcl-2 and a concomitant loss of mitochondrial membrane potential. Furthermore, we find that the anti-apoptotic effect of the pro-survival cytokine CD40 results in the abrogation of TGFβ-mediated Bim induction. Our data provide the first evidence of Bim expression levels that are increased by the addition of a pro-apoptotic cytokine, TGFβ, and also suggest that the TGFβ−specific transcription factor Smad3 plays a role in mediating Bim expression levels and apoptosis.
Gary M. Wildey - One of the best experts on this subject based on the ideXlab platform.
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smad3 potentiates transforming growth factor β tgfβ induced apoptosis and expression of the bh3 only protein bim in wehi 231 b lymphocytes
Journal of Biological Chemistry, 2003Co-Authors: Gary M. Wildey, Supriya Patil, Philip H. HoweAbstract:Transforming growth factor-beta (TGFbeta) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance. Here we show that exogenous overexpression of Smad3 potentiates TGFbeta-induced apoptosis and expression of the pro-apoptotic protein Bim in WEHI 231 B lymphocytes. Overexpression of dominant-negative forms of Smad3 abrogate these TGFbeta-induced responses. We also demonstrate that TGFbeta induces Bim protein expression concomitant with its induction of apoptosis in the mouse progenitor B lymphocyte Cell Line, Ba/F3. Enhanced expression of Bim protein induced by TGFbeta is associated with an increased association of Bim with Bcl-2 and a concomitant loss of mitochondrial membrane potential. Furthermore, we find that the anti-apoptotic effect of the pro-survival cytokine CD40 results in the abrogation of TGFbeta-mediated Bim induction. Our data provide the first evidence of Bim expression levels that are increased by the addition of a pro-apoptotic cytokine, TGFbeta, and also suggest that the TGFbeta-specific transcription factor Smad3 plays a role in mediating Bim expression levels and apoptosis.
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Smad3 Potentiates Transforming Growth Factor β (TGFβ)-induced Apoptosis and Expression of the BH3-only Protein Bim in WEHI 231 B Lymphocytes
Journal of Biological Chemistry, 2003Co-Authors: Gary M. Wildey, Supriya Patil, Philip H. HoweAbstract:Abstract Transforming growth factor-β (TGFβ) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance. Here we show that exogenous overexpression of Smad3 potentiates TGFβ-induced apoptosis and expression of the pro-apoptotic protein Bim in WEHI 231 B lymphocytes. Overexpression of dominant-negative forms of Smad3 abrogate these TGFβ-induced responses. We also demonstrate that TGFβ induces Bim protein expression concomitant with its induction of apoptosis in the mouse progenitor B lymphocyte Cell Line, Ba/F3. Enhanced expression of Bim protein induced by TGFβ is associated with an increased association of Bim with Bcl-2 and a concomitant loss of mitochondrial membrane potential. Furthermore, we find that the anti-apoptotic effect of the pro-survival cytokine CD40 results in the abrogation of TGFβ-mediated Bim induction. Our data provide the first evidence of Bim expression levels that are increased by the addition of a pro-apoptotic cytokine, TGFβ, and also suggest that the TGFβ−specific transcription factor Smad3 plays a role in mediating Bim expression levels and apoptosis.
Gary J. Nabel - One of the best experts on this subject based on the ideXlab platform.
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Kaposi’s Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor Confers Resistance to the Antiproliferative Effect of Interferon-α
Molecular medicine (Cambridge Mass.), 1998Co-Authors: C. Clay Flowers, Scarlett P. Flowers, Gary J. NabelAbstract:Background Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes a 442 amino acid polypeptide-desig-nated viral interferon regulatory factor (vIRF) that displays homology to members of the interferon regulatory factor (IRF) family that bind to consensus interferon sequences and transactivate Cellular genes that can modulate growth inhibition. Studies were conducted to determine whether vIRF affects the growth suppression mediated by interferon-α (IFN-α) in a human B lymphocyte Cell Line.
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Kaposi’s Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor Confers Resistance to the Antiproliferative Effect of Interferon-α
Molecular Medicine, 1998Co-Authors: C. Clay Flowers, Scarlett P. Flowers, Gary J. NabelAbstract:Background Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes a 442 amino acid polypeptide-desig-nated viral interferon regulatory factor (vIRF) that displays homology to members of the interferon regulatory factor (IRF) family that bind to consensus interferon sequences and transactivate Cellular genes that can modulate growth inhibition. Studies were conducted to determine whether vIRF affects the growth suppression mediated by interferon- α (IFN- α ) in a human B lymphocyte Cell Line. Materials and Methods The human B lymphocyte Cell Line Daudi, which is sensitive to the antiproliferative effects of IFN-α, was stably transfected to express vIRF, and the proliferative response of vIRF expressing Cells to IFN-α was compared with controls. The effect of vIRF on IRF-1 transactivation was analyzed by co-transfection of an IFN- ± -responsive chloramphenicol acetyltransferase reporter and expression plasmids encoding IRF-1 and vIRF. Electrophoretic mobility shift assays were conducted to determine whether vIRF interferes with the DNA binding activity of IRF-1. Results Daudi human B lymphocyte Cells expressing vIRF were resistant to the antiproliferative effects of IFN-α, whereas wild-type Daudi or Daudi Cells transformed with vector DNA were growth inhibited by IFN- α . The activation of an interferon-responsive reporter by IFN- α or IRF-1 was repressed by expression of vIRF. IRF-1 DNA binding activity was unaffected by vIRF, and vIRF alone did not bind to the interferon consensus sequence. Conclusions These studies revealed that vERF functions to inhibit interferon-mediated growth control of a human B lymphocyte Cell Line by targeting IRF-1 transactivation of interferon-inducible genes. Since KSHV is a B lymphotropic herpesvirus associated with two forms of B lymphocyte neoplasms, these effects of vIRF likely contribute to B Cell oncogenesis associated with KSHV infection.
Roberto Docampo - One of the best experts on this subject based on the ideXlab platform.
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the acidocalcisome inositol 1 4 5 trisphosphate receptor of trypanosoma brucei is stimulated by luminal polyphosphate hydrolysis products
Journal of Biological Chemistry, 2019Co-Authors: Evgeniy Potapenko, Nuria Waddington Negrao, Guozhong Huang, Roberto DocampoAbstract:Acidocalcisomes are acidic calcium stores rich in polyphosphate (polyP) and are present in trypanosomes and also in a diverse range of other organisms. Ca2+ is released from these organelles through a channel, inositol 1,4,5-trisphosphate receptor (TbIP3R), which is essential for growth and infectivity of the parasite Trypanosoma brucei However, the mechanism by which TbIP3R controls Ca2+ release is unclear. In this work, we expressed TbIP3R in a chicken B lymphocyte Cell Line in which the genes for all three vertebrate IP3Rs were stably ablated (DT40-3KO). We show that IP3-mediated Ca2+ release depends on Ca2+ but not on ATP concentration and is inhibited by heparin, caffeine, and 2-aminomethoxydiphenyl borate (2-APB). Excised patch clamp recordings from nuclear membranes of DT40 Cells expressing only TbIP3R disclosed that luminal inorganic orthophosphate (Pi) or pyrophosphate (PPi), and neutral or alkaLine pH can stimulate IP3-generated currents. In contrast, polyP or acidic pH did not induce these currents, and nuclear membranes obtained from Cells expressing rat IP3R were unresponsive to polyP or its hydrolysis products. Our results are consistent with the notion that polyP hydrolysis products within acidocalcisomes or alkalinization of their luminal pH activate TbIP3R and Ca2+ release. We conclude that TbIP3R is well-adapted to its role as the major Ca2+ release channel of acidocalcisomes in T. brucei.
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acidocalcisomes of trypanosoma brucei have an inositol 1 4 5 trisphosphate receptor that is required for growth and infectivity
Proceedings of the National Academy of Sciences of the United States of America, 2013Co-Authors: Guozhong Huang, Paula J Bartlett, Andrew P Thomas, Silvia N J Moreno, Roberto DocampoAbstract:Acidocalcisomes are acidic calcium stores rich in polyphosphate and found in a diverse range of organisms. The mechanism of Ca(2+) release from these organelles was unknown. Here we present evidence that Trypanosoma brucei acidocalcisomes possess an inositol 1,4,5-trisphosphate receptor (TbIP(3)R) for Ca(2+) release. Localization studies in Cell Lines expressing TbIP(3)R in its endogenous locus fused to an epitope tag revealed its partial colocalization with the vacuolar proton pyrophosphatase, a marker of acidocalcisomes. IP(3) was able to stimulate Ca(2+) release from a chicken B-Lymphocyte Cell Line in which the genes for all three vertebrate IP(3)Rs have been stably ablated (DT40-3KO) and that were stably expressing TbIP(3)R, providing evidence of its function. IP(3) was also able to release Ca(2+) from permeabilized trypanosomes or isolated acidocalcisomes and photolytic release of IP(3) in intact trypanosomes loaded with Fluo-4 elicited a transient Ca(2+) increase in their cytosol. Ablation of TbIP(3)R by RNA interference caused a significant reduction of IP(3)-mediated Ca(2+) release in trypanosomes and resulted in defects in growth in culture and infectivity in mice. Taken together, the data provide evidence of the presence of a functional IP(3)R as a Ca(2+) release channel in acidocalcisomes of trypanosomes and suggest that a Ca(2+) signaling pathway that involves acidocalcisomes is required for growth and establishment of infection.
Supriya Patil - One of the best experts on this subject based on the ideXlab platform.
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smad3 potentiates transforming growth factor β tgfβ induced apoptosis and expression of the bh3 only protein bim in wehi 231 b lymphocytes
Journal of Biological Chemistry, 2003Co-Authors: Gary M. Wildey, Supriya Patil, Philip H. HoweAbstract:Transforming growth factor-beta (TGFbeta) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance. Here we show that exogenous overexpression of Smad3 potentiates TGFbeta-induced apoptosis and expression of the pro-apoptotic protein Bim in WEHI 231 B lymphocytes. Overexpression of dominant-negative forms of Smad3 abrogate these TGFbeta-induced responses. We also demonstrate that TGFbeta induces Bim protein expression concomitant with its induction of apoptosis in the mouse progenitor B lymphocyte Cell Line, Ba/F3. Enhanced expression of Bim protein induced by TGFbeta is associated with an increased association of Bim with Bcl-2 and a concomitant loss of mitochondrial membrane potential. Furthermore, we find that the anti-apoptotic effect of the pro-survival cytokine CD40 results in the abrogation of TGFbeta-mediated Bim induction. Our data provide the first evidence of Bim expression levels that are increased by the addition of a pro-apoptotic cytokine, TGFbeta, and also suggest that the TGFbeta-specific transcription factor Smad3 plays a role in mediating Bim expression levels and apoptosis.
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Smad3 Potentiates Transforming Growth Factor β (TGFβ)-induced Apoptosis and Expression of the BH3-only Protein Bim in WEHI 231 B Lymphocytes
Journal of Biological Chemistry, 2003Co-Authors: Gary M. Wildey, Supriya Patil, Philip H. HoweAbstract:Abstract Transforming growth factor-β (TGFβ) is a potent growth inhibitor and inducer of apoptosis in B lymphocytes and is essential for immune regulation and maintenance of self-tolerance. Here we show that exogenous overexpression of Smad3 potentiates TGFβ-induced apoptosis and expression of the pro-apoptotic protein Bim in WEHI 231 B lymphocytes. Overexpression of dominant-negative forms of Smad3 abrogate these TGFβ-induced responses. We also demonstrate that TGFβ induces Bim protein expression concomitant with its induction of apoptosis in the mouse progenitor B lymphocyte Cell Line, Ba/F3. Enhanced expression of Bim protein induced by TGFβ is associated with an increased association of Bim with Bcl-2 and a concomitant loss of mitochondrial membrane potential. Furthermore, we find that the anti-apoptotic effect of the pro-survival cytokine CD40 results in the abrogation of TGFβ-mediated Bim induction. Our data provide the first evidence of Bim expression levels that are increased by the addition of a pro-apoptotic cytokine, TGFβ, and also suggest that the TGFβ−specific transcription factor Smad3 plays a role in mediating Bim expression levels and apoptosis.