The Experts below are selected from a list of 861 Experts worldwide ranked by ideXlab platform
Tatsuro Irimura - One of the best experts on this subject based on the ideXlab platform.
-
A library of mutated Maackia Amurensis hemagglutinin distinguishes putative glycoforms of immunoglobulin A1 from IgA nephropathy patients.
Journal of proteome research, 2009Co-Authors: Keisuke Maenuma, Mijung Yim, Kunimitsu Komatsu, Mayumi Hoshino, Ayumi Tachiki-fujioka, Kazuo Takahashi, Yoshiyuki Hiki, Nicolai V. Bovin, Tatsuro IrimuraAbstract:Ten genetically modified Maackia Amurensis hemagglutinin (MAH) clones at the carbohydrate-recognition loop were found to bind glycophorin A and a mucin mimetic with NeuAcα2−3Galβ1−3GalNAcα (monosialyl-T antigen) in different relative intensity. Binding profiles of these lectins to human serum IgA1 from healthy individuals and from IgA nephropathy patients were subjected to the cluster analysis. Two large groups, one with only healthy individuals and another with all IgA nephropathy patients, were generated. The results strongly suggest that the library of genetically modified MAH is a useful tool for serum diagnosis of IgA nephropathy.
-
Use of a library of mutated Maackia Amurensis hemagglutinin for profiling the cell lineage and differentiation
Proteomics, 2008Co-Authors: Keisuke Maenuma, Mijung Yim, Kunimitsu Komatsu, Mayumi Hoshino, Nicolai V. Bovin, Yoriko Takahashi, Tatsuro IrimuraAbstract:Thirty-five variant lectins were prepared by mutations of two amino acids within the carbohydrate-recognition domain of Maackia Amurensis hemagglutinin (MAH). Each lectin showed unique carbohydrate specificity according to their bindings to soluble polyacrylamide with various mono- and oligosaccharides and to glycophorin A. The relative intensity of the bindings of carcinoma, myeloid, fibroblastic, and melanoma cells to immobilized MAH variant lectins was examined. Each cell line showed distinct profiles regarding the number of cells bound to wild-type and 35 MAH variants and the differences and the similarities in these binding profiles were quantitatively documented by the cluster analysis. The cell lines were classified into several groups and these groups surprisingly corresponded to the lineage of the cells. These results indicated that a library of mutated MAH is useful as a tool for the profiling of various cells based on the variations of the surface glycans.
-
Sialic Acid-Binding Motif of Maackia Amurensis Lectins
Journal of biochemistry, 1997Co-Authors: Kazuo Yamamoto, Yukiko Konami, Tatsuro IrimuraAbstract:Maackia Amurensis hemagglutinin (MAH) and leukoagglutinin (MAL) are leguminous lectins which recognize carbohydrate chains containing sialic acid residues linked alpha2,3 to penultimate galactose residues. In the present investigation, cDNA clones encoding MAL were isolated from a cDNA library constructed from germinated Maackia Amurensis seeds and sequenced. From the reading frame of the cloned cDNAs, MAL was predicted to be composed of 287 amino acid residues, and showed strong similarity to MAH (86.2% identity). In leguminous lectins, most amino acid residues involved in sugar-binding were previously shown to be conserved. However, in both MAL and MAH lectins, the conserved glycine and asparagine were shown to be substituted by lysine and aspartic acid, respectively. Substitutions were made at position 105 and/or 135 of MAH to examine the roles of amino acid residues postulated to be important in binding to sialic acids. Recombinant MAH bound to the sialic acid-containing CB-II glycopeptide of human glycophorin A. By contrast, mutant lectins with lysine-105 substituted with glycine and/or aspartic acid-135 with asparagine did not bind to sialic acid residues. This indicates that these characteristic substitutions are important in sialic acid binding.
-
A unique amino acid sequence involved in the putative carbohydrate-binding domain of a legume lectin specific for sialylated carbohydrate chains: primary sequence determination of Maackia Amurensis hemagglutinin (MAH).
Journal of Biochemistry, 1994Co-Authors: Yukiko Konami, Chizu Ishida, Toshiaki Osawa, Kazuo Yamamoto, Tatsuro IrimuraAbstract:: The primary sequence of 247 amino acids of Maackia Amurensis hemagglutinin (MAH) was determined using a protein sequencer. After digestion with endoproteinase Lys-C, Asp-N, Arg-C, or Glu-C of MAH, the resulting peptides were purified by reversed phase high performance liquid chromatography (HPLC) and then subjected to sequence analysis. The primary sequence of MAH was compared with those of several legume lectins, and it was found that the amino acid sequence of the putative carbohydrate-binding domain of MAH exhibited a high degree of homology with those of di-N-acetylchitobiose-binding Cytisus sessilifolius lectin I (CSA-I), Laburnum alpinum lectin I (LAA-I), and Ulex europaeus lectin II (UEA-II). In the legume lectins whose primary sequences have already been determined several amino acid residues involved in carbohydrate-binding were found to be conserved. Very interestingly, in the primary sequence of MAH, one amino acid residue corresponding to the conserved amino acid, asparagine, in the primary sequences of all other legume lectins was shown to be substituted by aspartic acid. This is the first report of the occurrence of an exceptional amino acid residue among the conserved amino acid residues in the carbohydrate-binding domain of the legume lectins.
-
strong affinity of Maackia Amurensis hemagglutinin mah for sialic acid containing ser thr linked carbohydrate chains of n terminal octapeptides from human glycophorin a
FEBS Letters, 1994Co-Authors: Yukiko Konami, Toshiaki Osawa, Kazuo Yamamoto, Tatsuro IrimuraAbstract:The interaction of the Maackia Amurensis hemagglutinin (MAH) with various glycopeptides and oligosaccharides was investigated by means of immobilized lectin affinity chromatography. An amino terminal octapeptide obtained from human glycophorin A having three Neu5Acα→3Galβ1→3(Neu5Acα2→6)GalNAc tetrasaccharide chains, designated as CB-II, was found to have an extremely strong affinity for MAH. Therefore, it is strongly suggested that hemagglutination by MAH was caused by its interaction with Ser/Thr-linked carbohydrate chains of human glycophorin A on erythrocyte membranes.
Gary S Goldberg - One of the best experts on this subject based on the ideXlab platform.
-
effects of Maackia Amurensis seed lectin masl on oral squamous cell carcinoma oscc gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2021Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Effects of Maackia Amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2020Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Purpose Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Methods Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. Results MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Conclusions Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Evidence that Maackia Amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression.
Research square, 2020Co-Authors: Stephanie A Sheehan, Kelly L Hamilton, Edward P Retzbach, Premalatha Balachandran, Harini Krishnan, Paola Leone, Gary S GoldbergAbstract:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia Amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
Kelly L Hamilton - One of the best experts on this subject based on the ideXlab platform.
-
evidence that Maackia Amurensis seed lectin masl exerts pleiotropic actions on oral squamous cells with potential to inhibit sars cov 2 infection and covid 19 disease progression
Experimental Cell Research, 2021Co-Authors: Stephanie A Sheehan, Kelly L Hamilton, Edward P Retzbach, Premalatha Balachandran, Harini Krishnan, Paola Leone, Moises Lopezgonzalez, Shraddha Suryavanshi, Pradeep Kumar, Riccardo RussoAbstract:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 2.7 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia Amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. In addition, we report that MASL also inhibits SARS-CoV-2 infection of kidney epithelial cells in culture. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
-
effects of Maackia Amurensis seed lectin masl on oral squamous cell carcinoma oscc gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2021Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Effects of Maackia Amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2020Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Purpose Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Methods Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. Results MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Conclusions Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Evidence that Maackia Amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression.
Research square, 2020Co-Authors: Stephanie A Sheehan, Kelly L Hamilton, Edward P Retzbach, Premalatha Balachandran, Harini Krishnan, Paola Leone, Gary S GoldbergAbstract:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia Amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
Stephanie A Sheehan - One of the best experts on this subject based on the ideXlab platform.
-
evidence that Maackia Amurensis seed lectin masl exerts pleiotropic actions on oral squamous cells with potential to inhibit sars cov 2 infection and covid 19 disease progression
Experimental Cell Research, 2021Co-Authors: Stephanie A Sheehan, Kelly L Hamilton, Edward P Retzbach, Premalatha Balachandran, Harini Krishnan, Paola Leone, Moises Lopezgonzalez, Shraddha Suryavanshi, Pradeep Kumar, Riccardo RussoAbstract:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 2.7 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia Amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. In addition, we report that MASL also inhibits SARS-CoV-2 infection of kidney epithelial cells in culture. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
-
effects of Maackia Amurensis seed lectin masl on oral squamous cell carcinoma oscc gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2021Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Effects of Maackia Amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2020Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Purpose Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Methods Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. Results MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Conclusions Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Evidence that Maackia Amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression.
Research square, 2020Co-Authors: Stephanie A Sheehan, Kelly L Hamilton, Edward P Retzbach, Premalatha Balachandran, Harini Krishnan, Paola Leone, Gary S GoldbergAbstract:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia Amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
Edward P Retzbach - One of the best experts on this subject based on the ideXlab platform.
-
evidence that Maackia Amurensis seed lectin masl exerts pleiotropic actions on oral squamous cells with potential to inhibit sars cov 2 infection and covid 19 disease progression
Experimental Cell Research, 2021Co-Authors: Stephanie A Sheehan, Kelly L Hamilton, Edward P Retzbach, Premalatha Balachandran, Harini Krishnan, Paola Leone, Moises Lopezgonzalez, Shraddha Suryavanshi, Pradeep Kumar, Riccardo RussoAbstract:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 125 million confirmed COVID-19 cases that have caused over 2.7 million deaths worldwide as of March 2021. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia Amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. In addition, we report that MASL also inhibits SARS-CoV-2 infection of kidney epithelial cells in culture. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
-
effects of Maackia Amurensis seed lectin masl on oral squamous cell carcinoma oscc gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2021Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Effects of Maackia Amurensis seed lectin (MASL) on oral squamous cell carcinoma (OSCC) gene expression and transcriptional signaling pathways
Journal of Cancer Research and Clinical Oncology, 2020Co-Authors: Kelly L Hamilton, Stephanie A Sheehan, Edward P Retzbach, Premalatha Balachandran, Clinton A. Timmerman, Garret B. Gianneschi, Patrick J. Tempera, Gary S GoldbergAbstract:Purpose Oral cancer causes over 120,000 deaths annually and affects the quality of life for survivors. Over 90% of oral cancers are derived from oral squamous cell carcinoma cells (OSCCs) which are generally resistant to standard cytotoxic chemotherapy agents. OSCC cells often exhibit increased TGFβ and PDPN receptor activity compared to nontransformed oral epithelial cells. Maackia Amurensis seed lectin (MASL) can target the PDPN receptor and has been identified as a novel agent that can be used to treat oral cancer. However, mechanisms by which MASL inhibits OSCC progression are not yet clearly defined. Methods Here, we performed cell migration and cytotoxicity assays to assess the effects of MASL on OSCC motility and viability at physiologically relevant concentrations. We then performed comprehensive transcriptome analysis combined with transcription factor reporter assays to investigate the how MASL affects OSCC gene expression at these concentration. Key data were then confirmed by western blotting to evaluate the effects of MASL on gene expression and kinase signaling activity at the protein level. Results MASL significantly affected the expression of about 27% of approximately 15,000 genes found to be expressed by HSC-2 cells used to model OSCC cells in this study. These genes affected by MASL include members of the TGFβ–SMAD, JAK–STAT, and Wnt–βCTN signaling pathways. In particular, MASL decreased expression of PDPN, SOX2, and SMAD5 at the RNA and protein levels. MASL also inhibited SMAD and MAPK activity, and exhibited potential for combination therapy with doxorubicin and 5-fluorouracil. Conclusions Taken together, results from this study indicate that MASL decreases activity of JAK–STAT, TGFβ–SMAD, and Wnt–βCTN signaling pathways to inhibit OSCC growth and motility. These data suggest that further studies should be undertaken to determine how MASL may also be used alone and in combination with other agents to treat oral cancer.
-
Evidence that Maackia Amurensis seed lectin (MASL) exerts pleiotropic actions on oral squamous cells to inhibit SARS-CoV-2 infection and COVID-19 disease progression.
Research square, 2020Co-Authors: Stephanie A Sheehan, Kelly L Hamilton, Edward P Retzbach, Premalatha Balachandran, Harini Krishnan, Paola Leone, Gary S GoldbergAbstract:COVID-19 was declared an international public health emergency in January, and a pandemic in March of 2020. There are over 23 million confirmed COVID-19 cases that have cause over 800 thousand deaths worldwide as of August 19th, 2020. COVID-19 is caused by the SARS-CoV-2 virus. SARS-CoV-2 presents a surface "spike" protein that binds to the ACE2 receptor to infect host cells. In addition to the respiratory tract, SARS-Cov-2 can also infect cells of the oral mucosa, which also express the ACE2 receptor. The spike and ACE2 proteins are highly glycosylated with sialic acid modifications that direct viral-host interactions and infection. Maackia Amurensis seed lectin (MASL) has a strong affinity for sialic acid modified proteins and can be used as an antiviral agent. Here, we report that MASL targets the ACE2 receptor, decreases ACE2 expression and glycosylation, suppresses binding of the SARS-CoV-2 spike protein, and decreases expression of inflammatory mediators by oral epithelial cells that cause ARDS in COVID-19 patients. This work identifies MASL as an agent with potential to inhibit SARS-CoV-2 infection and COVID-19 related inflammatory syndromes.
