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Michael A Cahill - One of the best experts on this subject based on the ideXlab platform.
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the emerging role of Progesterone Receptor membrane component 1 pgrmc1 in cancer biology
Biochimica et Biophysica Acta, 2016Co-Authors: Michael A Cahill, Jalal A Jazayeri, Susan M Catalano, Shinya Toyokuni, Zaklina Kovacevic, Des R RichardsonAbstract:Progesterone Receptor membrane component 1 (PGRMC1) is a multi-functional protein with a heme-binding moiety related to that of cytochrome b5, which is a putative Progesterone Receptor. The recently solved PGRMC1 structure revealed that heme-binding involves coordination by a tyrosinate ion at Y113, and induces dimerization which is stabilized by hydrophobic stacking of heme on adjacent monomers. Dimerization is required for association with cytochrome P450 (cyP450) enzymes, which mediates chemoresistance to doxorubicin and may be responsible for PGRMC1's anti-apoptotic activity. Here we review the multiple attested involvement of PGRMC1 in diverse functions, including regulation of cytochrome P450, steroidogenesis, vesicle trafficking, Progesterone signaling and mitotic spindle and cell cycle regulation. Its wide range of biological functions is attested to particularly by its emerging association with cancer and Progesterone-responsive female reproductive tissues. PGRMC1 exhibits all the hallmarks of a higher order nexus signal integration hub protein. It appears capable of acting as a detector that integrates information from kinase/phosphatase pathways with heme and CO levels and probably redox status.
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Progesterone Receptor membrane component 1 an integrative review
The Journal of Steroid Biochemistry and Molecular Biology, 2007Co-Authors: Michael A CahillAbstract:Progesterone Receptor membrane component 1 (PGRMC1) contains a cytochrome b5 domain fold and belongs to the so-called membrane-associated Progesterone Receptor (MAPR) protein family that is widespread in eukaryotes. PGRMC1 and the related PGRMC2 mammalian family member diverged sometime after the evolution of segmented metazoan body plan and the appearance of vertebrates. Therefore PGRMC1 might be expected to be involved in some ancient eukaryotic processes, as well as more modern functions related to multicellularity and tissue interactions. Perhaps this explains the perplexing diversity of contexts where PGRMC1 has been observed, apparently being involved in different cellular processes at various sub-cellular locations. This review attempts to collate and interpret these observations. Ironically, despite being the archetypal member of the MAPR family, it has yet to be demonstrated that PGRMC1 exhibits specific Progesterone binding. Potential roles of heme and steroid/sterol ligands are reviewed, as well as the implications of apparent target sequences within PGRMC1 for binding by SH2- and SH3-domain proteins as well as kinases. These motifs are modelled using the cytochrome b5 domain NMR structure of the Arabidopsis protein 1J03, implicating a possible function for PGRMC1 as an adaptor protein involved in regulating protein interactions and intracellular signal transduction and/or membrane trafficking. This interpretation is supported by the apparent presence of immunoReceptor tyrosine-based activation motif/ITAM sequences that are involved in endocytosis and vesicle targeting, and the colocalisation of PGRMC1 with caveolin and at the cytoplasmic membrane. Evidence for roles in disease, especially cancer, is also discussed.
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Progesterone Receptor membrane component 1 an integrative review
The Journal of Steroid Biochemistry and Molecular Biology, 2007Co-Authors: Michael A CahillAbstract:Progesterone Receptor membrane component 1 (PGRMC1) contains a cytochrome b5 domain fold and belongs to the so-called membrane-associated Progesterone Receptor (MAPR) protein family that is widespread in eukaryotes. PGRMC1 and the related PGRMC2 mammalian family member diverged sometime after the evolution of segmented metazoan body plan and the appearance of vertebrates. Therefore PGRMC1 might be expected to be involved in some ancient eukaryotic processes, as well as more modern functions related to multicellularity and tissue interactions. Perhaps this explains the perplexing diversity of contexts where PGRMC1 has been observed, apparently being involved in different cellular processes at various sub-cellular locations. This review attempts to collate and interpret these observations. Ironically, despite being the archetypal member of the MAPR family, it has yet to be demonstrated that PGRMC1 exhibits specific Progesterone binding. Potential roles of heme and steroid/sterol ligands are reviewed, as well as the implications of apparent target sequences within PGRMC1 for binding by SH2- and SH3-domain proteins as well as kinases. These motifs are modelled using the cytochrome b5 domain NMR structure of the Arabidopsis protein 1J03, implicating a possible function for PGRMC1 as an adaptor protein involved in regulating protein interactions and intracellular signal transduction and/or membrane trafficking. This interpretation is supported by the apparent presence of immunoReceptor tyrosine-based activation motif/ITAM sequences that are involved in endocytosis and vesicle targeting, and the colocalisation of PGRMC1 with caveolin and at the cytoplasmic membrane. Evidence for roles in disease, especially cancer, is also discussed.
Amy P. Murtha - One of the best experts on this subject based on the ideXlab platform.
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The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.
PLOS ONE, 2016Co-Authors: Liping Feng, Carla E. Ransom, Matthew K. Nazzal, Yi-ju Li, Tracy Truong, Lauren C. Potts, Patrick C. Seed, Terrence K. Allen, Amy P. MurthaAbstract:Ureaplasma parvum (U. parvum) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of Progesterone (P4) and a novel Progesterone Receptor, Progesterone Receptor membrane component 1 (PGRMC1), in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10−7 M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2) secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among amnion and chorion cells.
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Progesterone Receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine induced matrix metalloproteinase 9 activity in vitro
Reproductive Sciences, 2014Co-Authors: Terrence K. Allen, Liping Feng, Chad A Grotegut, Amy P. MurthaAbstract:Progesterone (P4) and the progestin, 17α-hydroxyProgesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical Progesterone Receptor (PGR) but instead a novel Progesterone Receptor, Progesterone Receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyProgesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyProgesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small inte...
Liping Feng - One of the best experts on this subject based on the ideXlab platform.
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The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.
PLOS ONE, 2016Co-Authors: Liping Feng, Carla E. Ransom, Matthew K. Nazzal, Yi-ju Li, Tracy Truong, Lauren C. Potts, Patrick C. Seed, Terrence K. Allen, Amy P. MurthaAbstract:Ureaplasma parvum (U. parvum) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of Progesterone (P4) and a novel Progesterone Receptor, Progesterone Receptor membrane component 1 (PGRMC1), in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10−7 M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2) secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among amnion and chorion cells.
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Progesterone Receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine induced matrix metalloproteinase 9 activity in vitro
Reproductive Sciences, 2014Co-Authors: Terrence K. Allen, Liping Feng, Chad A Grotegut, Amy P. MurthaAbstract:Progesterone (P4) and the progestin, 17α-hydroxyProgesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical Progesterone Receptor (PGR) but instead a novel Progesterone Receptor, Progesterone Receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyProgesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyProgesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small inte...
Jianfeng Ren - One of the best experts on this subject based on the ideXlab platform.
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genomic sequence analyses of classical and non classical lamprey Progesterone Receptor genes and the inference of homologous gene evolution in metazoans
BMC Evolutionary Biology, 2019Co-Authors: Jianfeng Ren, Yu Wen Chungdavidson, Liang JiaAbstract:Nuclear Progesterone Receptor (nPR) is an evolutionary innovation in vertebrates that mediates genomic responses to Progesterone. Vertebrates also respond to Progesterone via membrane Progesterone Receptors (mPRs) or membrane associated Progesterone Receptors (MAPRs) through rapid nongenomic mechanisms. Lampreys are extant agnathan vertebrates, residing at the evolutionary juncture where vertebrates diverged from invertebrates. A survey of the Progesterone Receptor (PR) gene sequences in lamprey genomes would inform PR gene evolutionary events during the transition from invertebrates to vertebrates. In this study, we annotated sequences of one nPR, four mPR (β, γ, δ and e) and four MAPR genes from genomes of two lamprey species (Petromyzon marinus and Lethenteron japonicum). To infer the origin and evolutionary history of PR genes, we constructed phylogenetic trees of PR homologous sequences across representative species of metazoans. Phylogenetic analyses revealed that the mPRγ gene first appeared in non-bilaterians, and the mPRβ gene likely arose from a duplication of mPRγ. On the other hand, the mPRγ gene gave rise to the mPRδ and e genes much later in the vertebrate lineage. In addition, the mPRα gene first appeared in cartilaginous fishes, likely derived from duplication of mPRβ after the agnathan-gnathostome divergence. All known MAPR genes were present in the lamprey genomes. Progesterone Receptor membrane component 1 (PGRMC1), neudesin and neuferricin genes probably evolved in parallel in non-bilaterians, whereas two copies of PGRMC genes probably derived from duplication of ancestral PGRMC1 sequence and appeared before the speciation of lampreys. Non-classical mPR and MAPR genes first evolved in non-bilaterians and classical nPR genes evolved later in basal vertebrates. Sequence repertoires for membrane Progesterone Receptor genes in vertebrates likely originated from an ancestral metazoan sequence and expanded via several duplication events.
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Genomic sequence analyses of classical and non-classical lamprey Progesterone Receptor genes and the inference of homologous gene evolution in metazoans
'Springer Science and Business Media LLC', 2019Co-Authors: Jianfeng Ren, Yu-wen Chung-davidson, Liang JiaAbstract:Abstract Background Nuclear Progesterone Receptor (nPR) is an evolutionary innovation in vertebrates that mediates genomic responses to Progesterone. Vertebrates also respond to Progesterone via membrane Progesterone Receptors (mPRs) or membrane associated Progesterone Receptors (MAPRs) through rapid nongenomic mechanisms. Lampreys are extant agnathan vertebrates, residing at the evolutionary juncture where vertebrates diverged from invertebrates. A survey of the Progesterone Receptor (PR) gene sequences in lamprey genomes would inform PR gene evolutionary events during the transition from invertebrates to vertebrates. Results In this study, we annotated sequences of one nPR, four mPR (β, γ, δ and ε) and four MAPR genes from genomes of two lamprey species (Petromyzon marinus and Lethenteron japonicum). To infer the origin and evolutionary history of PR genes, we constructed phylogenetic trees of PR homologous sequences across representative species of metazoans. Phylogenetic analyses revealed that the mPRγ gene first appeared in non-bilaterians, and the mPRβ gene likely arose from a duplication of mPRγ. On the other hand, the mPRγ gene gave rise to the mPRδ and ε genes much later in the vertebrate lineage. In addition, the mPRα gene first appeared in cartilaginous fishes, likely derived from duplication of mPRβ after the agnathan-gnathostome divergence. All known MAPR genes were present in the lamprey genomes. Progesterone Receptor membrane component 1 (PGRMC1), neudesin and neuferricin genes probably evolved in parallel in non-bilaterians, whereas two copies of PGRMC genes probably derived from duplication of ancestral PGRMC1 sequence and appeared before the speciation of lampreys. Conclusions Non-classical mPR and MAPR genes first evolved in non-bilaterians and classical nPR genes evolved later in basal vertebrates. Sequence repertoires for membrane Progesterone Receptor genes in vertebrates likely originated from an ancestral metazoan sequence and expanded via several duplication events
Terrence K. Allen - One of the best experts on this subject based on the ideXlab platform.
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The Role of Progesterone and a Novel Progesterone Receptor, Progesterone Receptor Membrane Component 1, in the Inflammatory Response of Fetal Membranes to Ureaplasma parvum Infection.
PLOS ONE, 2016Co-Authors: Liping Feng, Carla E. Ransom, Matthew K. Nazzal, Yi-ju Li, Tracy Truong, Lauren C. Potts, Patrick C. Seed, Terrence K. Allen, Amy P. MurthaAbstract:Ureaplasma parvum (U. parvum) is gaining recognition as an important pathogen for chorioamnionitis and preterm premature rupture of membranes. We aimed to investigate the roles of Progesterone (P4) and a novel Progesterone Receptor, Progesterone Receptor membrane component 1 (PGRMC1), in the response of fetal membranes to U. parvum. Fetal membrane cells (amnion, chorion and decidua) were isolated and confirmed to be free of Mycoplasmataceae. Cells were treated with U. parvum (5x106 CFU), and adherence was quantified by qPCR. Amnion and chorion cells were transfected with scrambled siRNA or validated PGRMC1 siRNA for 72h. Cells were then treated with U. parvum for 4h with or without pretreatment with P4 (10−7 M) or ethanol for 1h. Interleukin-8 (IL-8), matrix metalloproteinase 9 (MMP9) and cyclooxygenase (COX-2) mRNA expression were quantified by qRT-PCR. Culture medium was harvested and analyzed for IL-8 and prostaglandin (PGE2) secretion by ELISA and MMP9 activity by zymography. U. parvum had a mean adherence of 15.0±0.6%, 16.9± 3.7% and 4.7±0.3% in cultured amnion, chorion and decidua cells, respectively. Exposure to U. parvum elicited significant inflammatory responses including induction of IL-8, COX-2, PGE2 and MMP9. A possible role of PGRMC1 was identified in the inhibition of U. parvum-stimulated COX-2 and MMP9 mRNA expression in chorion cells and MMP9 activity in amnion cells. On the other hand, it might enhance the U. parvum-stimulated IL-8 protein secretion in amnion cells. P4, mediated through PGRMC1, significantly inhibited U. Parvum-induced MMP9 mRNA and COX-2 mRNA expression in chorion cells. P4 appeared to attenuate U. parvum induced IL-8 mRNA expression in chorion cells, but this P4 effect might not mediated through PGRMC1. In summary, U. parvum preferentially adheres to and induces inflammatory responses in chorion and amnion cells. P4 and PGRMC1 appear to differentially modulate the inflammatory responses induced by U. parvum among amnion and chorion cells.
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Progesterone Receptor membrane component 1 as the mediator of the inhibitory effect of progestins on cytokine induced matrix metalloproteinase 9 activity in vitro
Reproductive Sciences, 2014Co-Authors: Terrence K. Allen, Liping Feng, Chad A Grotegut, Amy P. MurthaAbstract:Progesterone (P4) and the progestin, 17α-hydroxyProgesterone caproate, are clinically used to prevent preterm births (PTBs); however, their mechanism of action remains unclear. Cytokine-induced matrix metalloproteinase 9 (MMP-9) activity plays a key role in preterm premature rupture of the membranes and PTB. We demonstrated that the primary chorion cells and the HTR8/SVneo cells (cytotrophoblast cell line) do not express the classical Progesterone Receptor (PGR) but instead a novel Progesterone Receptor, Progesterone Receptor membrane component 1 (PGRMC1), whose role remains unclear. Using HTR8/SVneo cells in culture, we further demonstrated that 6 hours pretreatment with medroxyProgesterone acetate (MPA) and dexamethasone (Dex) but not P4 or 17α-hydroxyProgesterone hexanoate significantly attenuated tumor necrosis factor α-induced MMP-9 activity after a 24-hour incubation period. The inhibitory effect of MPA, but not Dex, was attenuated when PGRMC1 expression was successfully reduced by PGRMC1 small inte...