The Experts below are selected from a list of 202077 Experts worldwide ranked by ideXlab platform
Aránzazu Del Campo - One of the best experts on this subject based on the ideXlab platform.
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Exogenous Supply of Hsp47 Triggers Fibrillar Collagen Deposition in Skin Cell Cultures in Vitro
BMC Molecular and Cell Biology, 2020Co-Authors: Essak S. Khan, Shrikrishnan Sankaran, Lorena Llontop, Aránzazu Del CampoAbstract:Background Collagen is a structural protein that provides mechanical stability and defined architectures to Skin. In collagen-based Skin disorders this stability is lost, either due to mutations in collagens or in the chaperones involved in collagen assembly. This leads to chronic wounds, Skin fragility, and blistering. Existing approaches to treat such conditions rely on administration of small molecules to simulate collagen production, like 4-phenylbutyrate (4-PBA) or growth factors like TGF-β. However, these molecules are not specific for collagen synthesis, and result in unsolicited side effects. Hsp47 is a collagen-specific chaperone with a major role in collagen biosynthesis. Expression levels of Hsp47 correlate with collagen deposition. This article explores the stimulation of collagen deposition by exogenously supplied Hsp47 (collagen specific chaperone) to Skin Cells, including specific collagen subtypes quantification. Results Here we quantify the collagen deposition level and the types of deposited collagens after Hsp47 stimulation in different in vitro cultures of Cells from human Skin tissue (fibroblasts NHDF, keratinocytes HaCat and endothelial Cells HDMEC) and mouse fibroblasts (L929 and MEF). We find upregulated deposition of fibrillar collagen subtypes I, III and V after Hsp47 delivery. Network collagen IV deposition was enhanced in HaCat and HDMECs, while fibril-associated collagen XII was not affected by the increased intraCellular Hsp47 levels. The deposition levels of fibrillar collagen were Cell-dependent i.e. Hsp47-stimulated fibroblasts deposited significantly higher amount of fibrillar collagen than Hsp47-stimulated HaCat and HDMECs. Conclusions A 3-fold enhancement of collagen deposition was observed in fibroblasts upon repeated dosage of Hsp47 within the first 6 days of culture. Our results provide fundamental understanding towards the idea of using Hsp47 as therapeutic protein to treat collagen disorders.
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Exogenous supply of Hsp47 triggers fibrillar collagen deposition in Skin Cell cultures in vitro
2019Co-Authors: Essak S. Khan, Shrikrishnan Sankaran, Lorena Llontop, Aránzazu Del CampoAbstract:Abstract Background Collagen is a structural protein that provides mechanical stability and defined architectures to Skin. In collagen-based Skin disorders like Epidermolysis bullosa, EDS the ability to offer such stability is lost either due to mutations in collagens or defect in the chaperones involved in collagen assembly, which leads to chronic wounds, Skin fragility, and blisters. Existing approaches to study and develop therapy against such conditions are the use of small molecules like 4-phenylbutyrate (4-PBA) or growth factors like TGF-β. However, these approaches are not collagen specific resulting in unsolicited responses. Therefore, a collagen specific booster is required to guide the correct folding and deposition of collagen in a highly regulated manner. Hsp47 is a chaperone with a major role in collagen biosynthesis. Expression levels of Hsp47 correlate with collagen production. This article explores the stimulation of collagen deposition by exogenously supplied Hsp47 (collagen specific chaperone) in Skin Cells, including specific collagen subtypes quantification. Results Here we quantify the collagen deposition level and the type of deposited collagens by different Cell types from Skin tissue (fibroblasts NHDF, L929 and MEF, keratinocytes HaCat and endothelial Cells HDMEC) after Hsp47 stimulation. We find upregulated deposition of fibrillar collagen subtypes I, III and V after Hsp47 delivery. Network collagen IV deposition was enhanced in HaCat and HDMECs and fibril-associated collagen XII were not affected by the increased Hsp47 intraCellular levels. The deposition levels of fibrillar collagen were Cell-dependent i.e. Hsp47-stimulated fibroblasts deposited significantly higher amount of fibrillar collagen than Hsp47-stimulated HaCat and HDMECs. Conclusions A 3-fold enhancement of collagen deposition was observed in fibroblasts upon repeated dosage of Hsp47 within the first 6 days of culture. Our results provide fundamental understanding towards the idea of using Hsp47 as therapeutic protein to treat collagen disorders.
Vicente Micol - One of the best experts on this subject based on the ideXlab platform.
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protective effects of citrus and rosemary extracts on uv induced damage in Skin Cell model and human volunteers
Journal of Photochemistry and Photobiology B-biology, 2014Co-Authors: Almudena Perezsanchez, Enrique Barrajoncatalan, Nuria Caturla, Julian Castillo, O Benaventegarcia, M Alcaraz, Vicente MicolAbstract:Abstract Ultraviolet radiation absorbed by the epidermis is the major cause of various cutaneous disorders, including photoaging and Skin cancers. Although topical sunscreens may offer proper Skin protection, dietary plant compounds may significantly contribute to lifelong protection of Skin health, especially when unconsciously sun UV exposed. A combination of rosemary and citrus bioflavonoids extracts was used to inhibit UV harmful effects on human HaCaT keratinocytes and in human volunteers after oral intake. Survival of HaCaT Cells after UVB radiation was higher in treatments using the combination of extracts than in those performed with individual extracts, indicating potential synergic effects. The combination of extracts also decreased UVB-induced intraCellular radical oxygen species (ROS) and prevented DNA damage in HaCaT Cells by comet assay and decreased chromosomal aberrations in X-irradiated human lymphocytes. The oral daily consumption of 250 mg of the combination by human volunteers revealed a significant minimal erythema dose (MED) increase after eight weeks (34%, p
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protective effects of citrus and rosemary extracts on uv induced damage in Skin Cell model and human volunteers
Journal of Photochemistry and Photobiology B-biology, 2014Co-Authors: Almudena Perezsanchez, Nuria Caturla, M Alcaraz, Enrique Arrajoncatala, Julia Castillo, O Enaventegarcia, Vicente MicolAbstract:Ultraviolet radiation absorbed by the epidermis is the major cause of various cutaneous disorders, including photoaging and Skin cancers. Although topical sunscreens may offer proper Skin protection, dietary plant compounds may significantly contribute to lifelong protection of Skin health, especially when unconsciously sun UV exposed. A combination of rosemary and citrus bioflavonoids extracts was used to inhibit UV harmful effects on human HaCaT keratinocytes and in human volunteers after oral intake. Survival of HaCaT Cells after UVB radiation was higher in treatments using the combination of extracts than in those performed with individual extracts, indicating potential synergic effects. The combination of extracts also decreased UVB-induced intraCellular radical oxygen species (ROS) and prevented DNA damage in HaCaT Cells by comet assay and decreased chromosomal aberrations in X-irradiated human lymphocytes. The oral daily consumption of 250 mg of the combination by human volunteers revealed a significant minimal erythema dose (MED) increase after eight weeks (34%, p<0.05). Stronger protection was achieved after 12 weeks (56%, p<0.01). The combination of citrus flavonoids and rosemary polyphenols and diterpenes may be considered as an ingredient for oral photoprotection. Their mechanism of action may deserve further attention.
Donna D Zhang - One of the best experts on this subject based on the ideXlab platform.
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cinnamoyl based nrf2 activators targeting human Skin Cell photo oxidative stress
Free Radical Biology and Medicine, 2008Co-Authors: Georg T Wondrak, Christopher M Cabello, Nicole Villeneuve, Shirley L Zhang, Yanjie Li, Donna D ZhangAbstract:Strong experimental evidence suggests the involvement of photo-oxidative stress mediated by reactive oxygen species as a crucial mechanism of solar damage relevant to human Skin photoaging and photocarcinogenesis. Based on the established role of antioxidant response element (ARE)-mediated gene expression in cancer chemoprevention, we tested the hypothesis that small molecule Nrf2-activators may serve a photo-chemopreventive role by targeting Skin Cell photo-oxidative stress. A luciferase-based reporter gene assay was used as a primary screen for the identification of novel agents that modulate the Nrf2-Keap1 signaling pathway. A series of cinnamoyl-based electrophilic Michael acceptors including cinnamic aldehyde and methyl-1-cinnamoyl-5-oxo-2-pyrrolidine-carboxylate was identified as potent Nrf2-activators. Hit confirmation was performed in a secondary screen, based on immunodetection of Nrf2 protein upregulation in human Hs27 Skin fibroblasts, HaCaT keratinocytes, and primary Skin keratinocytes. Bioefficacy profiling of positive test compounds in Skin Cells demonstrated compound-induced upregulation of hemeoxygenase I and NAD(P)H-quinone oxidoreductase, two Nrf2 target genes involved in the Cellular antioxidant response. Pretreatment with cinnamoyl-based Nrf2-activators suppressed intraCellular oxidative stress and protected against photo-oxidative induction of apoptosis in Skin Cells exposed to high doses of singlet oxygen. Our pilot studies suggest feasibility of developing cinnamoyl-based Nrf2-activators as novel photo-chemopreventive agents targeting Skin Cell photo-oxidative stress.
Georg T Wondrak - One of the best experts on this subject based on the ideXlab platform.
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cinnamoyl based nrf2 activators targeting human Skin Cell photo oxidative stress
Free Radical Biology and Medicine, 2008Co-Authors: Georg T Wondrak, Christopher M Cabello, Nicole Villeneuve, Shirley L Zhang, Yanjie Li, Donna D ZhangAbstract:Strong experimental evidence suggests the involvement of photo-oxidative stress mediated by reactive oxygen species as a crucial mechanism of solar damage relevant to human Skin photoaging and photocarcinogenesis. Based on the established role of antioxidant response element (ARE)-mediated gene expression in cancer chemoprevention, we tested the hypothesis that small molecule Nrf2-activators may serve a photo-chemopreventive role by targeting Skin Cell photo-oxidative stress. A luciferase-based reporter gene assay was used as a primary screen for the identification of novel agents that modulate the Nrf2-Keap1 signaling pathway. A series of cinnamoyl-based electrophilic Michael acceptors including cinnamic aldehyde and methyl-1-cinnamoyl-5-oxo-2-pyrrolidine-carboxylate was identified as potent Nrf2-activators. Hit confirmation was performed in a secondary screen, based on immunodetection of Nrf2 protein upregulation in human Hs27 Skin fibroblasts, HaCaT keratinocytes, and primary Skin keratinocytes. Bioefficacy profiling of positive test compounds in Skin Cells demonstrated compound-induced upregulation of hemeoxygenase I and NAD(P)H-quinone oxidoreductase, two Nrf2 target genes involved in the Cellular antioxidant response. Pretreatment with cinnamoyl-based Nrf2-activators suppressed intraCellular oxidative stress and protected against photo-oxidative induction of apoptosis in Skin Cells exposed to high doses of singlet oxygen. Our pilot studies suggest feasibility of developing cinnamoyl-based Nrf2-activators as novel photo-chemopreventive agents targeting Skin Cell photo-oxidative stress.
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DNA damage by carbonyl stress in human Skin Cells.
Mutation research, 2003Co-Authors: Michael J Roberts, Georg T Wondrak, Daniel Cervantes Laurean, Myron K Jacobson, Elaine L JacobsonAbstract:Reactive carbonyl species (RCS) are potent mediators of Cellular carbonyl stress originating from endogenous chemical processes such as lipid peroxidation and glycation. Skin deterioration as observed in photoaging and diabetes has been linked to accumulative protein damage from glycation, but the effects of carbonyl stress on Skin Cell genomic integrity are ill defined. In this study, the genotoxic effects of acute carbonyl stress on HaCaT keratinocytes and CF3 fibroblasts were assessed. Administration of the alpha-dicarbonyl compounds glyoxal and methylglyoxal as physiologically relevant RCS inhibited Skin Cell proliferation, led to intra-Cellular protein glycation as evidenced by the accumulation of N(epsilon)-(carboxymethyl)-L-lysine (CML) in histones, and caused extensive DNA strand cleavage as assessed by the comet assay. These effects were prevented by treatment with the carbonyl scavenger D-penicillamine. Both glyoxal and methylglyoxal damaged DNA in intact Cells. Glyoxal caused DNA strand breaks while methylglyoxal produced extensive DNA-protein cross-linking as evidenced by pronounced nuclear condensation and total suppression of comet formation. Glycation by glyoxal and methylglyoxal resulted in histone cross-linking in vitro and induced oxygen-dependent cleavage of plasmid DNA, which was partly suppressed by the hydroxyl scavenger mannitol. We suggest that a chemical mechanism of Cellular DNA damage by carbonyl stress occurs in which histone glycoxidation is followed by reactive oxygen induced DNA stand breaks. The genotoxic potential of RCS in cultured Skin Cells and its suppression by a carbonyl scavenger as described in this study have implications for Skin damage and carcinogenesis and its prevention by agents selective for carbonyl stress.
Essak S. Khan - One of the best experts on this subject based on the ideXlab platform.
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Exogenous Supply of Hsp47 Triggers Fibrillar Collagen Deposition in Skin Cell Cultures in Vitro
BMC Molecular and Cell Biology, 2020Co-Authors: Essak S. Khan, Shrikrishnan Sankaran, Lorena Llontop, Aránzazu Del CampoAbstract:Background Collagen is a structural protein that provides mechanical stability and defined architectures to Skin. In collagen-based Skin disorders this stability is lost, either due to mutations in collagens or in the chaperones involved in collagen assembly. This leads to chronic wounds, Skin fragility, and blistering. Existing approaches to treat such conditions rely on administration of small molecules to simulate collagen production, like 4-phenylbutyrate (4-PBA) or growth factors like TGF-β. However, these molecules are not specific for collagen synthesis, and result in unsolicited side effects. Hsp47 is a collagen-specific chaperone with a major role in collagen biosynthesis. Expression levels of Hsp47 correlate with collagen deposition. This article explores the stimulation of collagen deposition by exogenously supplied Hsp47 (collagen specific chaperone) to Skin Cells, including specific collagen subtypes quantification. Results Here we quantify the collagen deposition level and the types of deposited collagens after Hsp47 stimulation in different in vitro cultures of Cells from human Skin tissue (fibroblasts NHDF, keratinocytes HaCat and endothelial Cells HDMEC) and mouse fibroblasts (L929 and MEF). We find upregulated deposition of fibrillar collagen subtypes I, III and V after Hsp47 delivery. Network collagen IV deposition was enhanced in HaCat and HDMECs, while fibril-associated collagen XII was not affected by the increased intraCellular Hsp47 levels. The deposition levels of fibrillar collagen were Cell-dependent i.e. Hsp47-stimulated fibroblasts deposited significantly higher amount of fibrillar collagen than Hsp47-stimulated HaCat and HDMECs. Conclusions A 3-fold enhancement of collagen deposition was observed in fibroblasts upon repeated dosage of Hsp47 within the first 6 days of culture. Our results provide fundamental understanding towards the idea of using Hsp47 as therapeutic protein to treat collagen disorders.
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Exogenous supply of Hsp47 triggers fibrillar collagen deposition in Skin Cell cultures in vitro
2019Co-Authors: Essak S. Khan, Shrikrishnan Sankaran, Lorena Llontop, Aránzazu Del CampoAbstract:Abstract Background Collagen is a structural protein that provides mechanical stability and defined architectures to Skin. In collagen-based Skin disorders like Epidermolysis bullosa, EDS the ability to offer such stability is lost either due to mutations in collagens or defect in the chaperones involved in collagen assembly, which leads to chronic wounds, Skin fragility, and blisters. Existing approaches to study and develop therapy against such conditions are the use of small molecules like 4-phenylbutyrate (4-PBA) or growth factors like TGF-β. However, these approaches are not collagen specific resulting in unsolicited responses. Therefore, a collagen specific booster is required to guide the correct folding and deposition of collagen in a highly regulated manner. Hsp47 is a chaperone with a major role in collagen biosynthesis. Expression levels of Hsp47 correlate with collagen production. This article explores the stimulation of collagen deposition by exogenously supplied Hsp47 (collagen specific chaperone) in Skin Cells, including specific collagen subtypes quantification. Results Here we quantify the collagen deposition level and the type of deposited collagens by different Cell types from Skin tissue (fibroblasts NHDF, L929 and MEF, keratinocytes HaCat and endothelial Cells HDMEC) after Hsp47 stimulation. We find upregulated deposition of fibrillar collagen subtypes I, III and V after Hsp47 delivery. Network collagen IV deposition was enhanced in HaCat and HDMECs and fibril-associated collagen XII were not affected by the increased Hsp47 intraCellular levels. The deposition levels of fibrillar collagen were Cell-dependent i.e. Hsp47-stimulated fibroblasts deposited significantly higher amount of fibrillar collagen than Hsp47-stimulated HaCat and HDMECs. Conclusions A 3-fold enhancement of collagen deposition was observed in fibroblasts upon repeated dosage of Hsp47 within the first 6 days of culture. Our results provide fundamental understanding towards the idea of using Hsp47 as therapeutic protein to treat collagen disorders.
