Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1
Carnosine (β-alanyl-L-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Carnosine is involved in cellular defense mechanisms against oxidative stress, including the inhibition of amyloid-beta (Aβ) aggregation a...
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2019-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | http://www.mdpi.com/2073-4409/8/1/64 |
| _version_ | 1797706584778866688 |
|---|---|
| author | Giuseppe Caruso Claudia G. Fresta Nicolò Musso Mariaconcetta Giambirtone Margherita Grasso Simona F. Spampinato Sara Merlo Filippo Drago Giuseppe Lazzarino Maria A. Sortino Susan M. Lunte Filippo Caraci |
| author_facet | Giuseppe Caruso Claudia G. Fresta Nicolò Musso Mariaconcetta Giambirtone Margherita Grasso Simona F. Spampinato Sara Merlo Filippo Drago Giuseppe Lazzarino Maria A. Sortino Susan M. Lunte Filippo Caraci |
| author_sort | Giuseppe Caruso |
| collection | DOAJ |
| description | Carnosine (β-alanyl-L-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Carnosine is involved in cellular defense mechanisms against oxidative stress, including the inhibition of amyloid-beta (Aβ) aggregation and the scavenging of reactive species. Microglia play a central role in the pathogenesis of Alzheimer’s disease, promoting neuroinflammation through the secretion of inflammatory mediators and free radicals. However, the effects of carnosine on microglial cells and neuroinflammation are not well understood. In the present work, carnosine was tested for its ability to protect BV-2 microglial cells against oligomeric Aβ1-42-induced oxidative stress and inflammation. Carnosine prevented cell death in BV-2 cells challenged with Aβ oligomers through multiple mechanisms. Specifically, carnosine lowered the oxidative stress by decreasing NO and O2−• intracellular levels as well as the expression of iNOS and Nox enzymes. Carnosine also decreased the secretion of pro-inflammatory cytokines such as IL-1β, simultaneously rescuing IL-10 levels and increasing the expression and the release of TGF-β1. Carnosine also prevented Aβ-induced neurodegeneration in mixed neuronal cultures challenged with Aβ oligomers, and these neuroprotective effects were completely abolished by SB431542, a selective inhibitor of the type-1 TGF-β receptor. Our data suggest a multimodal mechanism of action of carnosine underlying its protective effects on microglial cells against Aβ toxicity with a key role of TGF-β1 in mediating these protective effects. |
| first_indexed | 2024-03-12T05:54:27Z |
| format | Article |
| id | doaj.art-6576816879f04530b4ef9a943001353d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-12T05:54:27Z |
| publishDate | 2019-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-6576816879f04530b4ef9a943001353d2023-09-03T04:48:04ZengMDPI AGCells2073-44092019-01-01816410.3390/cells8010064cells8010064Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1Giuseppe Caruso0Claudia G. Fresta1Nicolò Musso2Mariaconcetta Giambirtone3Margherita Grasso4Simona F. Spampinato5Sara Merlo6Filippo Drago7Giuseppe Lazzarino8Maria A. Sortino9Susan M. Lunte10Filippo Caraci11Oasi Research Institute—IRCCS, 94018 Troina, ItalyRalph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047-1620, USABio-nanotech Research and Innovation Tower (BRIT), University of Catania, 95125 Catania, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyOasi Research Institute—IRCCS, 94018 Troina, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Division of Medical Biochemistry, University of Catania, 95125 Catania, ItalyDepartment of Biomedical and Biotechnological Sciences, Section of Pharmacology, University of Catania, 95125 Catania, ItalyRalph N. Adams Institute for Bioanalytical Chemistry, University of Kansas, Lawrence, KS 66047-1620, USAOasi Research Institute—IRCCS, 94018 Troina, ItalyCarnosine (β-alanyl-L-histidine), a dipeptide, is an endogenous antioxidant widely distributed in excitable tissues like muscles and the brain. Carnosine is involved in cellular defense mechanisms against oxidative stress, including the inhibition of amyloid-beta (Aβ) aggregation and the scavenging of reactive species. Microglia play a central role in the pathogenesis of Alzheimer’s disease, promoting neuroinflammation through the secretion of inflammatory mediators and free radicals. However, the effects of carnosine on microglial cells and neuroinflammation are not well understood. In the present work, carnosine was tested for its ability to protect BV-2 microglial cells against oligomeric Aβ1-42-induced oxidative stress and inflammation. Carnosine prevented cell death in BV-2 cells challenged with Aβ oligomers through multiple mechanisms. Specifically, carnosine lowered the oxidative stress by decreasing NO and O2−• intracellular levels as well as the expression of iNOS and Nox enzymes. Carnosine also decreased the secretion of pro-inflammatory cytokines such as IL-1β, simultaneously rescuing IL-10 levels and increasing the expression and the release of TGF-β1. Carnosine also prevented Aβ-induced neurodegeneration in mixed neuronal cultures challenged with Aβ oligomers, and these neuroprotective effects were completely abolished by SB431542, a selective inhibitor of the type-1 TGF-β receptor. Our data suggest a multimodal mechanism of action of carnosine underlying its protective effects on microglial cells against Aβ toxicity with a key role of TGF-β1 in mediating these protective effects.http://www.mdpi.com/2073-4409/8/1/64carnosinemicrogliaAlzheimer’s diseaseneurodegenerationneuroinflammationreactive oxygen and nitrogen speciesoxidative stressTGF-β1 |
| spellingShingle | Giuseppe Caruso Claudia G. Fresta Nicolò Musso Mariaconcetta Giambirtone Margherita Grasso Simona F. Spampinato Sara Merlo Filippo Drago Giuseppe Lazzarino Maria A. Sortino Susan M. Lunte Filippo Caraci Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1 Cells carnosine microglia Alzheimer’s disease neurodegeneration neuroinflammation reactive oxygen and nitrogen species oxidative stress TGF-β1 |
| title | Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1 |
| title_full | Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1 |
| title_fullStr | Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1 |
| title_full_unstemmed | Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1 |
| title_short | Carnosine Prevents Aβ-Induced Oxidative Stress and Inflammation in Microglial Cells: A Key Role of TGF-β1 |
| title_sort | carnosine prevents aβ induced oxidative stress and inflammation in microglial cells a key role of tgf β1 |
| topic | carnosine microglia Alzheimer’s disease neurodegeneration neuroinflammation reactive oxygen and nitrogen species oxidative stress TGF-β1 |
| url | http://www.mdpi.com/2073-4409/8/1/64 |
| work_keys_str_mv | AT giuseppecaruso carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT claudiagfresta carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT nicolomusso carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT mariaconcettagiambirtone carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT margheritagrasso carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT simonafspampinato carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT saramerlo carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT filippodrago carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT giuseppelazzarino carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT mariaasortino carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT susanmlunte carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 AT filippocaraci carnosinepreventsabinducedoxidativestressandinflammationinmicroglialcellsakeyroleoftgfb1 |