The Experts below are selected from a list of 481746 Experts worldwide ranked by ideXlab platform
S K Maheswaran - One of the best experts on this subject based on the ideXlab platform.
-
Biological Effects of two genetically defined leukotoxin mutants of mannheimia haemolytica
Microbial Pathogenesis, 2003Co-Authors: Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:Abstract Mannheimia(Pasteurella)haemolytica serotype 1 is the primary causative agent responsible for bovine pneumonic mannheimiosis, also known as shipping fever in cattle. The bacterium produces a variety of virulence factors, foremost of which is the exotoxic leukotoxin. The leukotoxin is a calcium-dependent cytolysin that is a member of the RTX (repeats in toxin) family and exhibits a narrow cell-type and species specificity and has Biological Effects only on ruminant leukocytes and platelets. The genetic organization of the leukotoxin is comprised of four genes: lktC , lktA , lktB and lktD . The lktA structural gene encodes the protoxin (pro-LktA) and lktC encodes a transacylase that post-translationally modifies the inactive pro-LktA to a Biologically active wild-type leukotoxin (LktA). The LktA has been implicated as the key factor that contributes to the pathogenesis of lung injury associated with the disease and considerable efforts have been employed in abrogating toxin function while retaining immunogenicity, with an eye towards design of attenuated vaccines. We hypothesized that the pro-LktA retains the ability to cause Biological Effects on target cells as has been reported in the case of the closely related RTX toxin α-hemolysin (HlyA). We also examined the Biological Effects of an amino-terminal truncation mutant leukotoxin ΔLktA on target cells. Thus the objectives of our study were to investigate whether two different mutant leukotoxins, one a nonacylated pro-LktA, and the other lacking 344 amino acids at the N-terminal end of the LktA protein; ΔLktA, are capable of (i) binding to the β2-integrin leukotoxin receptor, (ii) inducing the elevation of second messenger intracellular calcium ([Ca 2+ ] i ), and (iii) inducing inflammatory gene expression, reactive oxygen metabolites (ROMs) and cytolysis in target cells. Our results demonstrate that neither acylation nor the amino terminal 344 amino acids are required for LktA binding but are essential for LktA-induced [Ca 2+ ] i elevation, generation of ROM, generation of the inflammatory cytokine IL-8 and cytolysis in target cells.
-
mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes which induces Biological Effects
Infection and Immunity, 2001Co-Authors: Samithamby Jeyaseelan, Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces Biological Effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any Effects. These findings suggest that the specificity of LktA Effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to Biological Effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for Biological Effects. We used a Biologically inactive mutant leukotoxin (DeltaLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The DeltaLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3'-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced Biological Effects.
-
mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes which induces Biological Effects
Infection and Immunity, 2001Co-Authors: Samithamby Jeyaseelan, Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces Biological Effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any Effects. These findings suggest that the specificity of LktA Effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to Biological Effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for Biological Effects. We used a Biologically inactive mutant leukotoxin (ΔLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The ΔLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3′-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced Biological Effects.
Lukas Snopek - One of the best experts on this subject based on the ideXlab platform.
-
bioactive compounds antioxidant activity and Biological Effects of european cranberry vaccinium oxycoccos
Molecules, 2018Co-Authors: Tunde Jurikova, Stefan Balla, Sona Skrovankova, Jiri Mlcek, Lukas SnopekAbstract:Lesser known fruits or underutilized fruit species are recently of great research interest due to the presence of phytochemicals that manifest many Biological Effects. European cranberry, Vaccinium oxycoccos fruit, as an important representative of this group, is a valuable source of antioxidants and other Biologically active substances, similar to American cranberry (V. macrocarpon) which is well known and studied. European cranberry fruit is rich especially in polyphenolic compounds anthocyanins (12.4–207.3 mg/100 g fw), proanthocyanins (1.5–5.3 mg/100 g fw), and flavonols, especially quercetin (0.52–15.4 mg/100 g fw), which mostly contribute to the antioxidant activity of the fruit. Small cranberry is also important due to its various Biological Effects such as urinary tract protection (proanthocyanidins), antibacterial and antifungal properties (quercetin, proanthocyanidins, anthocyanins), cardioprotective (proanthocyanidins) and anticancer activities (proanthocyanidins), and utilization in food (juice drinks, jams, jellies, sauces, additive to meat products) and pharmacological industries, and in folk medicine.
-
bioactive compounds antioxidant activity and Biological Effects of european cranberry vaccinium oxycoccos
Molecules, 2018Co-Authors: Tunde Jurikova, Stefan Balla, Sona Skrovankova, Jiri Mlcek, Lukas SnopekAbstract:Lesser known fruits or underutilized fruit species are recently of great research interest due to the presence of phytochemicals that manifest many Biological Effects. European cranberry, Vaccinium oxycoccos fruit, as an important representative of this group, is a valuable source of antioxidants and other Biologically active substances, similar to American cranberry (V. macrocarpon) which is well known and studied. European cranberry fruit is rich especially in polyphenolic compounds anthocyanins (12.4–207.3 mg/100 g fw), proanthocyanins (1.5–5.3 mg/100 g fw), and flavonols, especially quercetin (0.52–15.4 mg/100 g fw), which mostly contribute to the antioxidant activity of the fruit. Small cranberry is also important due to its various Biological Effects such as urinary tract protection (proanthocyanidins), antibacterial and antifungal properties (quercetin, proanthocyanidins, anthocyanins), cardioprotective (proanthocyanidins) and anticancer activities (proanthocyanidins), and utilization in food (juice drinks, jams, jellies, sauces, additive to meat products) and pharmacological industries, and in folk medicine.
Samithamby Jeyaseelan - One of the best experts on this subject based on the ideXlab platform.
-
mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes which induces Biological Effects
Infection and Immunity, 2001Co-Authors: Samithamby Jeyaseelan, Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces Biological Effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any Effects. These findings suggest that the specificity of LktA Effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to Biological Effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for Biological Effects. We used a Biologically inactive mutant leukotoxin (DeltaLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The DeltaLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3'-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced Biological Effects.
-
mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes which induces Biological Effects
Infection and Immunity, 2001Co-Authors: Samithamby Jeyaseelan, Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces Biological Effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any Effects. These findings suggest that the specificity of LktA Effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to Biological Effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for Biological Effects. We used a Biologically inactive mutant leukotoxin (ΔLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The ΔLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3′-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced Biological Effects.
Tunde Jurikova - One of the best experts on this subject based on the ideXlab platform.
-
bioactive compounds antioxidant activity and Biological Effects of european cranberry vaccinium oxycoccos
Molecules, 2018Co-Authors: Tunde Jurikova, Stefan Balla, Sona Skrovankova, Jiri Mlcek, Lukas SnopekAbstract:Lesser known fruits or underutilized fruit species are recently of great research interest due to the presence of phytochemicals that manifest many Biological Effects. European cranberry, Vaccinium oxycoccos fruit, as an important representative of this group, is a valuable source of antioxidants and other Biologically active substances, similar to American cranberry (V. macrocarpon) which is well known and studied. European cranberry fruit is rich especially in polyphenolic compounds anthocyanins (12.4–207.3 mg/100 g fw), proanthocyanins (1.5–5.3 mg/100 g fw), and flavonols, especially quercetin (0.52–15.4 mg/100 g fw), which mostly contribute to the antioxidant activity of the fruit. Small cranberry is also important due to its various Biological Effects such as urinary tract protection (proanthocyanidins), antibacterial and antifungal properties (quercetin, proanthocyanidins, anthocyanins), cardioprotective (proanthocyanidins) and anticancer activities (proanthocyanidins), and utilization in food (juice drinks, jams, jellies, sauces, additive to meat products) and pharmacological industries, and in folk medicine.
-
bioactive compounds antioxidant activity and Biological Effects of european cranberry vaccinium oxycoccos
Molecules, 2018Co-Authors: Tunde Jurikova, Stefan Balla, Sona Skrovankova, Jiri Mlcek, Lukas SnopekAbstract:Lesser known fruits or underutilized fruit species are recently of great research interest due to the presence of phytochemicals that manifest many Biological Effects. European cranberry, Vaccinium oxycoccos fruit, as an important representative of this group, is a valuable source of antioxidants and other Biologically active substances, similar to American cranberry (V. macrocarpon) which is well known and studied. European cranberry fruit is rich especially in polyphenolic compounds anthocyanins (12.4–207.3 mg/100 g fw), proanthocyanins (1.5–5.3 mg/100 g fw), and flavonols, especially quercetin (0.52–15.4 mg/100 g fw), which mostly contribute to the antioxidant activity of the fruit. Small cranberry is also important due to its various Biological Effects such as urinary tract protection (proanthocyanidins), antibacterial and antifungal properties (quercetin, proanthocyanidins, anthocyanins), cardioprotective (proanthocyanidins) and anticancer activities (proanthocyanidins), and utilization in food (juice drinks, jams, jellies, sauces, additive to meat products) and pharmacological industries, and in folk medicine.
-
phenolic profile of edible honeysuckle berries genus lonicera and their Biological Effects
Molecules, 2011Co-Authors: Tunde Jurikova, Stefan Balla, Jiri Mlcek, Otakar Rop, Jiri Sochor, Ladislav Szekeres, Alzbeta Hegedusova, Jaromir Hubalek, Vojtech Adam, Rene KizekAbstract:The current status of research on polyphenolic compounds in the berries of edible honeysuckle and their Biological Effects, including recommended utilization, are reviewed. The major classes of phenolic compounds in the blue berried honeysuckle are flavonols (quercetin, rutin, quercitrin) and flavanes (proanthocyanidins, catechins) and anthocyanins. Cyanidin-3-glucoside and cyanidin-3-rutinoside are considered as major anthocyanidins in edible honeysuckle berries. Such a high level of antioxidant activity in the berries of different species of the genus Lonicera is especially due to the high level of polyphenolic compounds, especially anthocyanins. These berries seem to be prospective sources of health-supporting phytochemicals that exhibit beneficial anti-adherence and chemo-protective activities, thus they may provide protection against a number of chronic conditions, e.g., cancer, diabetes mellitus, tumour growth or cardiovascular and neurodegenerative diseases.
R E Briggs - One of the best experts on this subject based on the ideXlab platform.
-
Biological Effects of two genetically defined leukotoxin mutants of mannheimia haemolytica
Microbial Pathogenesis, 2003Co-Authors: Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:Abstract Mannheimia(Pasteurella)haemolytica serotype 1 is the primary causative agent responsible for bovine pneumonic mannheimiosis, also known as shipping fever in cattle. The bacterium produces a variety of virulence factors, foremost of which is the exotoxic leukotoxin. The leukotoxin is a calcium-dependent cytolysin that is a member of the RTX (repeats in toxin) family and exhibits a narrow cell-type and species specificity and has Biological Effects only on ruminant leukocytes and platelets. The genetic organization of the leukotoxin is comprised of four genes: lktC , lktA , lktB and lktD . The lktA structural gene encodes the protoxin (pro-LktA) and lktC encodes a transacylase that post-translationally modifies the inactive pro-LktA to a Biologically active wild-type leukotoxin (LktA). The LktA has been implicated as the key factor that contributes to the pathogenesis of lung injury associated with the disease and considerable efforts have been employed in abrogating toxin function while retaining immunogenicity, with an eye towards design of attenuated vaccines. We hypothesized that the pro-LktA retains the ability to cause Biological Effects on target cells as has been reported in the case of the closely related RTX toxin α-hemolysin (HlyA). We also examined the Biological Effects of an amino-terminal truncation mutant leukotoxin ΔLktA on target cells. Thus the objectives of our study were to investigate whether two different mutant leukotoxins, one a nonacylated pro-LktA, and the other lacking 344 amino acids at the N-terminal end of the LktA protein; ΔLktA, are capable of (i) binding to the β2-integrin leukotoxin receptor, (ii) inducing the elevation of second messenger intracellular calcium ([Ca 2+ ] i ), and (iii) inducing inflammatory gene expression, reactive oxygen metabolites (ROMs) and cytolysis in target cells. Our results demonstrate that neither acylation nor the amino terminal 344 amino acids are required for LktA binding but are essential for LktA-induced [Ca 2+ ] i elevation, generation of ROM, generation of the inflammatory cytokine IL-8 and cytolysis in target cells.
-
mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes which induces Biological Effects
Infection and Immunity, 2001Co-Authors: Samithamby Jeyaseelan, Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces Biological Effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any Effects. These findings suggest that the specificity of LktA Effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to Biological Effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for Biological Effects. We used a Biologically inactive mutant leukotoxin (DeltaLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The DeltaLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3'-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced Biological Effects.
-
mannheimia haemolytica leukotoxin activates a nonreceptor tyrosine kinase signaling cascade in bovine leukocytes which induces Biological Effects
Infection and Immunity, 2001Co-Authors: Samithamby Jeyaseelan, Praveen Thumbikat, R E Briggs, Mathur S Kannan, S K MaheswaranAbstract:The leukotoxin (LktA) produced by Mannheimia haemolytica binds to bovine lymphocyte function-associated antigen 1 (LFA-1) and induces Biological Effects in bovine leukocytes in a cellular and species-specific fashion. We have previously shown that LktA also binds to porcine LFA-1 without eliciting any Effects. These findings suggest that the specificity of LktA Effects must entail both binding to LFA-1 and activation of signaling pathways which are present in bovine leukocytes. However, the signaling pathways leading to Biological Effects upon LktA binding to LFA-1 have not been characterized. In this context, several reports have indicated that ligand binding to LFA-1 results in activation of a nonreceptor tyrosine kinase (NRTK) signaling cascade. We designed experiments with the following objectives: (i) to determine whether LktA binding to LFA-1 leads to activation of NRTKs, (ii) to examine whether LktA-induced NRTK activation is target cell specific, and (iii) to determine whether LktA-induced NRTK activation is required for Biological Effects. We used a Biologically inactive mutant leukotoxin (ΔLktA) for comparison with LktA. Our results indicate that LktA induces tyrosine phosphorylation (TP) of the CD18 tail of LFA-1 in bovine leukocytes. The ΔLktA mutant does not induce TP of the CD18 tail, albeit binding to bovine LFA-1. LktA-induced TP of the CD18 tail was attenuated by an NRTK inhibitor, herbimycin A; a phosphatidylinositol 3′-kinase (PI 3-kinase) inhibitor, wortmannin; and a Src kinase inhibitor, PP2, in a concentration-dependent manner. Furthermore, LktA induces TP of the CD18 tail in bovine, but not porcine, leukocytes. Moreover, LktA-induced intracellular calcium ([Ca2+]i) elevation was also inhibited by herbimycin A, wortmannin, and PP2. Thus, our data represent the first evidence that binding of LktA to bovine LFA-1 induces a species-specific NRTK signaling cascade involving PI 3-kinase and Src kinases and that this signaling cascade is required for LktA-induced Biological Effects.
