Protective Actions of Anserine Under Diabetic Conditions
In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine. Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by...
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| Published in: | International journal of molecular sciences Vol. 19; no. 9; p. 2751 |
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| Abstract | In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine.
Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured.
Anserine has a higher antioxidant capacity compared to carnosine (
< 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20⁻100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all
< 0.05).
Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy. |
|---|---|
| AbstractList | BACKGROUND/AIMSIn rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine.METHODSAntioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured.RESULTSAnserine has a higher antioxidant capacity compared to carnosine (p < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20⁻100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all p < 0.05).CONCLUSIONAnserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy. Background/Aims: In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine. Methods: Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured. Results: Anserine has a higher antioxidant capacity compared to carnosine (p < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20-100 mu M hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all p < 0.05). Conclusion: Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy. Background/Aims: In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine. Methods: Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured. Results: Anserine has a higher antioxidant capacity compared to carnosine ( p < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20–100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all p < 0.05). Conclusion: Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy. Background/Aims: In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine. Methods: Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured. Results: Anserine has a higher antioxidant capacity compared to carnosine (p < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20–100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all p < 0.05). Conclusion: Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy. In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of carnosine. Antioxidant activity was measured by oxygen radical absorbance capacity and oxygen stress response in human renal tubular cells (HK-2) by RT-PCR and Western-Immunoblotting. In wildtype (WT) and diabetic mice (db/db), the effect of short-term anserine treatment on blood glucose, proteinuria and vascular permeability was measured. Anserine has a higher antioxidant capacity compared to carnosine ( < 0.001). In tubular cells (HK-2) stressed with 25 mM glucose or 20⁻100 µM hydrogen peroxide, anserine but not carnosine, increased intracellular heat shock protein (Hsp70) mRNA and protein levels. In HK-2 cells stressed with glucose, co-incubation with anserine also increased hemeoxygenase (HO-1) protein and reduced total protein carbonylation, but had no effect on cellular sirtuin-1 and thioredoxin protein concentrations. Three intravenous anserine injections every 48 h in 12-week-old db/db mice, improved blood glucose by one fifth, vascular permeability by one third, and halved proteinuria (all < 0.05). Anserine is a potent antioxidant and activates the intracellular Hsp70/HO-1 defense system under oxidative and glycative stress. Short-term anserine treatment in diabetic mice improves glucose homeostasis and nephropathy. |
| Author | Thiel, Christian Volk, Nadine Schmitt, Claus Peter Fleming, Thomas Scuto, Maria Calabrese, Vittorio Weigand, Tim Modafferi, Sergio Baelde, Hans Peters, Verena Forsberg, Elisabete Trovato, Angela |
| AuthorAffiliation | 2 Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy; calabres@unict.it (V.C.); trovato@unict.it (A.T.); scuto@unict.it (M.S.) 1 Centre for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, 69120 Heidelberg, Germany; tim.weigand@med.uni-heidelberg.de (T.W.); christian.thiel@med.uni-heidelberg.de (C.T.); sergio.modafferi@gmail.com (S.M.); clauspeter.schmitt@med.uni-heidelberg.de (C.P.S.) 3 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden; elisabete.forsberg@su.se 5 Department of Pathology, Leiden University Medical Center, 2300RC L1Q Leiden, The Netherlands; J.J.Baelde@lumc.nl 4 Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, 69120 Heidelberg, Germany; Nadine.Volk@med.uni-heidelberg.de (N.V.); thomas.fleming@med.uni-heidelberg.de (T.F.) |
| AuthorAffiliation_xml | – name: 4 Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, 69120 Heidelberg, Germany; Nadine.Volk@med.uni-heidelberg.de (N.V.); thomas.fleming@med.uni-heidelberg.de (T.F.) – name: 5 Department of Pathology, Leiden University Medical Center, 2300RC L1Q Leiden, The Netherlands; J.J.Baelde@lumc.nl – name: 1 Centre for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, 69120 Heidelberg, Germany; tim.weigand@med.uni-heidelberg.de (T.W.); christian.thiel@med.uni-heidelberg.de (C.T.); sergio.modafferi@gmail.com (S.M.); clauspeter.schmitt@med.uni-heidelberg.de (C.P.S.) – name: 3 Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden; elisabete.forsberg@su.se – name: 2 Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy; calabres@unict.it (V.C.); trovato@unict.it (A.T.); scuto@unict.it (M.S.) |
| Author_xml | – sequence: 1 givenname: Verena surname: Peters fullname: Peters, Verena email: Verena.Peters@med.uni-heidelberg.de organization: Centre for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, 69120 Heidelberg, Germany. Verena.Peters@med.uni-heidelberg.de – sequence: 2 givenname: Vittorio surname: Calabrese fullname: Calabrese, Vittorio email: calabres@unict.it organization: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy. calabres@unict.it – sequence: 3 givenname: Elisabete surname: Forsberg fullname: Forsberg, Elisabete email: elisabete.forsberg@su.se organization: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, SE-106 91 Stockholm, Sweden. elisabete.forsberg@su.se – sequence: 4 givenname: Nadine surname: Volk fullname: Volk, Nadine email: Nadine.Volk@med.uni-heidelberg.de organization: Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, 69120 Heidelberg, Germany. Nadine.Volk@med.uni-heidelberg.de – sequence: 5 givenname: Thomas surname: Fleming fullname: Fleming, Thomas email: thomas.fleming@med.uni-heidelberg.de organization: Department of Medicine I and Clinical Chemistry, University Hospital of Heidelberg, 69120 Heidelberg, Germany. thomas.fleming@med.uni-heidelberg.de – sequence: 6 givenname: Hans surname: Baelde fullname: Baelde, Hans email: J.J.Baelde@lumc.nl organization: Department of Pathology, Leiden University Medical Center, 2300RC L1Q Leiden, The Netherlands. J.J.Baelde@lumc.nl – sequence: 7 givenname: Tim surname: Weigand fullname: Weigand, Tim email: tim.weigand@med.uni-heidelberg.de organization: Centre for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, 69120 Heidelberg, Germany. tim.weigand@med.uni-heidelberg.de – sequence: 8 givenname: Christian surname: Thiel fullname: Thiel, Christian email: christian.thiel@med.uni-heidelberg.de organization: Centre for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, 69120 Heidelberg, Germany. christian.thiel@med.uni-heidelberg.de – sequence: 9 givenname: Angela surname: Trovato fullname: Trovato, Angela email: trovato@unict.it organization: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy. trovato@unict.it – sequence: 10 givenname: Maria surname: Scuto fullname: Scuto, Maria email: scuto@unict.it organization: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy. scuto@unict.it – sequence: 11 givenname: Sergio surname: Modafferi fullname: Modafferi, Sergio email: sergio.modafferi@gmail.com, sergio.modafferi@gmail.com organization: Department of Biomedical and Biotechnological Sciences, School of Medicine, University of Catania, 95123 Catania, Italy. sergio.modafferi@gmail.com – sequence: 12 givenname: Claus Peter surname: Schmitt fullname: Schmitt, Claus Peter email: clauspeter.schmitt@med.uni-heidelberg.de organization: Centre for Paediatric and Adolescent Medicine, University Hospital of Heidelberg, 69120 Heidelberg, Germany. clauspeter.schmitt@med.uni-heidelberg.de |
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| Keywords | Hsp70 carnosine proteinuria anserine vascular permeability diabetes diabetic nephropathy |
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| Snippet | In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated form of... Background/Aims: In rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated... BACKGROUND/AIMSIn rodents, carnosine treatment improves diabetic nephropathy, whereas little is known about the role and function of anserine, the methylated... |
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| Title | Protective Actions of Anserine Under Diabetic Conditions |
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