The Experts below are selected from a list of 24462123 Experts worldwide ranked by ideXlab platform
Chihhsin Tang - One of the best experts on this subject based on the ideXlab platform.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
Showmei Chuang - One of the best experts on this subject based on the ideXlab platform.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
Chunhao Tsai - One of the best experts on this subject based on the ideXlab platform.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
Shihwei Wang - One of the best experts on this subject based on the ideXlab platform.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
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ctgf increases vascular endothelial growth factor dependent angiogenesis in human synovial fibroblasts by increasing mir 210 expression
Cell Death and Disease, 2014Co-Authors: Showmei Chuang, Chihhsin Tang, Chunhao Tsai, Shihwei WangAbstract:Connective tissue growth factor (CTGF, a.k.a. CCN2) is inflammatory mediator and abundantly expressed in osteoarthritis (OA). Angiogenesis is essential for OA progression. Here, we investigated the role of CTGF in vascular endothelial growth factor (VEGF) production and angiogenesis in OA synovial fibroblasts (OASFs). We showed that expression of CTGF and VEGF in synovial fluid were higher in OA patients than in controls. Directly applying CTGF to OASFs increased VEGF production then promoted endothelial progenitor cells tube formation and migration. CTGF induced VEGF by raising miR-210 expression via PI3K, AKT, ERK, and nuclear factor-κB (NF-κB)/ELK1 pathways. CTGF-mediating miR-210 upregulation repressed glycerol-3-phosphate dehydrogenase 1-like (GPD1L) expression and PHD activity and subsequently promoted hypoxia-inducible factor (HIF)-1α-dependent VEGF expression. Knockdown of CTGF decreased VEGF expression and abolished OASF-conditional medium-mediated angiogenesis in vitro as well as angiogenesis in chick chorioallantoic membrane and Matrigel-plug nude mice model in vivo. Taken together, our results suggest CTGF activates PI3K, AKT, ERK, and NF-κB/ELK1 pathway, leading to the upregulation of miR-210, contributing to inhibit GPD1L expression and prolyl hydroxylases 2 activity, promoting HIF-1α-dependent VEGF expression and angiogenesis in human synovial fibroblasts.
Stefan Hohmann - One of the best experts on this subject based on the ideXlab platform.
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roles of sugar alcohols in osmotic stress adaptation replacement of glycerol by mannitol and sorbitol in yeast
Plant Physiology, 1999Co-Authors: Bo Shen, Stefan Hohmann, Richard G Jensen, Hans J BohnertAbstract:For many organisms there is a correlation between increases of metabolites and osmotic stress tolerance, but the mechanisms that cause this protection are not clear. To understand the role of polyols, genes for bacterial mannitol-1-P dehydrogenase and apple sorbitol-6-P dehydrogenase were introduced into a Saccharomyces cerevisiae mutant deficient in glycerol synthesis. Sorbitol and mannitol provided some protection, but less than that generated by a similar concentration of glycerol generated by glycerol-3-P dehydrogenase (GPD1). Reduced protection by polyols suggested that glycerol had specific functions for which mannitol and sorbitol could not substitute, and that the absolute amount of the accumulating osmoticum might not be crucial. The retention of glycerol and mannitol/sorbitol, respectively, was a major difference. During salt stress, cells retained more of the six-carbon polyols than glycerol. We suggest that the loss of >98% of the glycerol synthesized could provide a safety valve that dissipates reducing power, while a similar high intracellular concentration of retained polyols would be less protective. To understand the role of glycerol in salt tolerance, salt-tolerant suppressor mutants were isolated from the glycerol-deficient strain. One mutant, sr13, partially suppressed the salt-sensitive phenotype of the glycerol-deficient line, probably due to a doubling of [K+] accumulating during stress. We compare these results to the “osmotic adjustment” concept typically applied to accumulating metabolites in plants. The accumulation of polyols may have dual functions: facilitating osmotic adjustment and supporting redox control.
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osmotic stress induced gene expression in saccharomyces cerevisiae requires msn1p and the novel nuclear factor hot1p
Molecular and Cellular Biology, 1999Co-Authors: Vladimir Reiser, Johan M Thevelein, Stefan Hohmann, Ulrike Gartner, Gustav Ammerer, Helmut RuisAbstract:The HOG (high-osmolarity glycerol response) mitogen-activated protein (MAP) kinase pathway plays a pivotal role in the adaptation of Saccharomyces cerevisiae to conditions of high external osmolarity. This is best illustrated by the fact that cells deficient in this pathway cannot proliferate on media containing high levels of osmotically active molecules (6). On the other hand, ectopic activation of the pathway is also detrimental for cell growth (19, 31). This situation has allowed an extensive genetic analysis, leading to the identification of many positive and negative elements of the HOG signaling pathway (19, 21, 24, 30, 31, 37–41, 60). The system relies on the input of two independent and structurally unrelated sensors whose signals converge at the level of the MAP kinase kinase Pbs2p, the direct activator of the MAP kinase Hog1p (reviewed in references 19 and 39). In addition to countering the effects of persistent high-osmolarity conditions, the HOG pathway also mediates short-term responses to fluctuations in the osmolarity of the environment. Sudden shifts to high osmolarity result in the accumulation of intracellular glycerol due to a combination of HOG pathway-regulated stimulation of glycerol synthesis (1, 6) and decreased glycerol efflux that seems to occur independently of the HOG MAP kinase (29, 53). One of the early HOG pathway-triggered events is the nuclear accumulation of Hog1p kinase (16, 43) followed by a distinct transcriptional response that over a time period of about 90 min to several hours (depending on the extent of osmotic challenge) transiently induces expression of genes encoding enzymes involved in glycerol synthesis, such as GPD1 and GPP2 (HOR2) (1, 2, 20, 36, 44). In addition, the HOG-mediated signal affects expression of genes whose products have a more general role in the protection from stress-induced damage, such as HSP104, which encodes a chaperonin (28); CTT1, which encodes cytoplasmic catalase (49); and HSP12, whose precise molecular function is unknown (51, 57). One of the major unresolved problems concerning this transcriptional response is the identity of the molecular targets recognized by the signaling pathway (19). This problem further extends to the question of whether and how short-term responses and long-term adaptation, both requiring the HOG pathway (44), are mechanistically connected. Many stress-responsive genes in yeast are regulated via a common promoter element called the stress response element (STRE). This element appears to be sufficient for mediating the transcriptional response to many different environmental challenges (33). Two redundantly acting transcription factors, Msn2p and Msn4p, that recognize this sequence have been identified (35, 48). In response to a large variety of stress situations, including osmotic stress, these factors are translocated to the nucleus, where they bind and activate target promoters such as those of the CTT1 or HSP12 gene (18). Although Msn2p and Msn4p enhance the expression of these genes, suggesting some connection to the HOG pathway, HOG pathway-mediated transcriptional activation can still be found in the absence of Msn2p and Msn4p function. The extent of Msn2p- and Msn4p-independent activation varies from promoter to promoter (this work and reference 35). Consequently, this pair of transcription factors cannot be the only ones responsible for high-osmolarity-induced gene expression. In the case of some yeast promoters, induction appears to be mediated by HOG pathway-dependent inactivation of Sko1p (34, 42, 45). Sko1p is a transcriptional repressor, which binds to CRE-like DNA elements and appears to tether the general repressors Tup1p and Ssn6p to promoters (34, 42). This system does not control expression of GPD1 (44, 45), and hence it is still unclear by which molecular mechanisms the Hog1p MAP kinase triggers induction of transcription of this type of target genes. This study shows that the hitherto-undescribed nuclear protein Hot1p is important for HOG pathway-dependent osmotic induction of genes encoding enzymes involved in yeast glycerol biosynthesis. A protein with a similar putative DNA-binding domain, Msn1p, contributes to both osmotic and heat stress induction of GPD1, CTT1, and HSP12. MSN1 has previously been isolated as a high-copy-number suppressor of snf1 mutants (14) and has been implicated in the regulation of iron uptake (12) and of pseudohyphal growth (26, 27). It has been shown to be a nuclear protein and to function as a transcriptional activator when fused to the DNA-binding domain of LexA (14). Our data suggest that together Hot1p and Msn1p mediate the bulk of the Msn2p- and Msn4p-independent osmotic stress activation of the genes GPD1, GPP2, CTT1, and HSP12.
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role of trehalose in survival of saccharomyces cerevisiae under osmotic stress
Microbiology, 1998Co-Authors: C G Hounsa, E V Brandt, Johan M Thevelein, Stefan Hohmann, Bernard A PriorAbstract:Trehalose is an enigmatic compound that accumulates in Saccharomyces cerevisiae and has been implicated in survival under various stress conditions by acting as membrane protectant, as a supplementary compatible solute or as a reserve carbohydrate that may be mobilized during stress. In this study, specific mutants in trehalose metabolism were used to evaluate whether trehalose contributes to survival under severe osmotic stress and generates the compatible solute glycerol under moderate osmotic stress. The survival under severe osmotic stress (0.866 a W, NaCI or sorbitol) of mutants was compared to that of the wild-type strain when cultivated to either the mid-exponential or the stationary growth phase on glucose, galactose or ethanol. Stationary-phase cells survived better than exponential-phase cells. The death rates of ethanol-grown cells were lower than those of galactose-grown cells, which in turn survived better than glucose-grown cells. There was a strong relationship between intracellular trehalose levels and resistance to osmotic stress. The mutant strains unable to produce trehalose (tps1Δ tps2Δ and tps1Δ hxk2 Δ) were more sensitive to severe osmotic stress (0.866 a W) than the isogenic wild-type strain, confirming a role for trehalose in survival. Hyperaccumulation of trehalose found in the nth1Δ and the nth1Δ gpd1Δ mutant strains, however, did not improve survival rates compared to the wild-type strain. When wild-type, nth1Δ and nth1Δ gpd1Δ cells were exposed to moderate osmotic stress (0.98 and 0.97 a W, NaCI), which permits growth, glycerol production did not appear to be related to the intracellular trehalose levels although glycerol levels increased more rapidly in nth1Δ cells than in wild-type cells during the initial response to osmotic stress. These data indicate that trehalose does not act as a reserve compound for glycerol synthesis under these conditions. No evidence was found for solutes other than glycerol and trehalose being significant for the survival of or growth by S. cerevisiae under osmotic stress conditions.
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role of trehalose in survival of saccharomyces cerevisiae under osmotic stress
Microbiology, 1998Co-Authors: C G Hounsa, E V Brandt, Johan M Thevelein, Stefan Hohmann, Bernard A PriorAbstract:Trehalose is an enigmatic compound that accumulates in Saccharomyces cerevisiae and has been implicated in survival under various stress conditions by acting as membrane protectant, as a supplementary compatible solute or as a reserve carbohydrate that may be mobilized during stress. In this study, specific mutants in trehalose metabolism were used to evaluate whether trehalose contributes to survival under severe osmotic stress and generates the compatible solute glycerol under moderate osmotic stress. The survival under severe osmotic stress (0.866 aw' NaCl or sorbitol) of mutants was compared to that of the wild-type strain when cultivated to either the mid-exponential or the stationary growth phase on glucose, galactose or ethanol. Stationary-phase cells survived better than exponential-phase cells. The death rates of ethanol-grown cells were lower than those of galactose-grown cells, which in turn survived better than glucose-grown cells. There was a strong relationship between intracellular trehalose levels and resistance to osmotic stress. The mutant strains unable to produce trehalose (tps1 delta tps2 delta and tps1 delta hxk2 delta) were more sensitive to severe osmotic stress (0.866 aw) than the isogenic wild-type strain, confirming a role for trehalose in survival. Hyperaccumulation of trehalose found in the nth1 delta and the nth1 delta gpd1 delta mutant strains, however, did not improve survival rates compared to the wild-type strain. When wild-type, nth1 delta and nth1 delta gpd1 delta cells were exposed to moderate osmotic stress (0.98 and 0.97 aw' NaCl), which permits growth, glycerol production did not appear to be related to the intracellular trehalose levels although glycerol levels increased more rapidly in nth1 delta cells than in wild-type cells during the initial response to osmotic stress. These data indicate that trehalose does not act as a reserve compound for glycerol synthesis under these conditions. No evidence was found for solutes other than glycerol and trehalose being significant for the survival of or growth by S. cerevisiae under osmotic stress conditions.
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fps1 a yeast member of the mip family of channel proteins is a facilitator for glycerol uptake and efflux and is inactive under osmotic stress
The EMBO Journal, 1995Co-Authors: K Luyten, Johan M Thevelein, Bernard A Prior, Jacobus Albertyn, W F Skibbe, J Ramos, Stefan HohmannAbstract:Abstract The Saccharomyces cerevisiae FPS1 gene, which encodes a channel protein belonging to the MIP family, has been isolated previously as a multicopy suppressor of the growth defect of the fdp1 mutant (allelic to GGS1/TPS1) on fermentable sugars. Here we show that overexpression of FPS1 enhances glycerol production. Enhanced glycerol production caused by overexpression of GPD1 encoding glycerol-3-phosphate dehydrogenase also suppressed the growth defect of ggs1/tps1 delta mutants, suggesting a novel role for glycerol production in the control of glycolysis. The suppression of ggs1/tps1 delta mutants by GPD1 depends on the presence of Fps1. Mutants lacking Fps1 accumulate a greater part of the glycerol intracellularly, indicating that Fps1 is involved in glycerol efflux. Glycerol-uptake experiments showed that the permeability of the yeast plasma membrane for glycerol consists of an Fps1-independent component probably due to simple diffusion and of an Fps1-dependent component representing facilitated diffusion. The Escherichia coli glycerol facilitator expressed in a yeast fps1 delta mutant can restore the characteristics of glycerol uptake, production and distribution fully, but restores only partially growth of a ggs1/tps1 delta fps1 delta double mutant on glucose. Fps1 appears to be closed under hyperosmotic stress when survival depends on intracellular accumulation of glycerol and apparently opens rapidly when osmostress is lifted. The osmostress-induced High Osmolarity Glycerol (HOG) response pathway is not required for inactivation of Fps1. We conclude that Fps1 is a regulated yeast glycerol facilitator controlling glycerol production and cytosolic concentration, and might have additional functions.
