title: PPARγ regulates inflammatory reaction by inhibiting the MAPK/NF-κB pathway in C2C12 skeletal muscle cells.
abstract: Excessive exercise induces an inflammatory response caused by oxidative stress, which delays recovery of damaged muscle fibers. The reduction of inflammatory response is important for skeletal muscle homeostasis. Peroxisome proliferator-activated receptor gamma (PPARγ) is an anti-inflammatory molecule, but the role of PPARγ in skeletal muscle as anti-inflammatory activity is not clear. Thus, this study examined the anti-inflammatory role of PPARγ against H2O2-induced oxidative stress in skeletal muscle. Sprague Dawley (SD) rats were exercised on a treadmill to induce oxidative stress. In vitro oxidative stress was evaluated in differentiated C2C12 cells stimulated using 200 μM H2O2. Inflammation-related molecules were determined by immunohistochemistry and Western blot analysis. Expressions of the inflammatory molecules tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase-2 (COX-2), and matrix metalloproteinase-2 (MMP-2) in muscles of the acute exercise group were highly increased. PPARγ was also highly expressed in these muscles. These inflammatory molecules were also markedly increased in C2C12 cells with H2O2stimulation. However, PPARγ overexpression in C2C12 transfected by Ad/PPARγ dramatically reduced the inflammatory molecules. PPARγ also enhanced the anti-oxidants molecules like Cu/Zn-SOD, Mn-SOD, and hemeoxygenase-1 by reducing the generation of ROS, even in the presence of H2O2. PPARγ displayed dual anti-inflammatory and anti-oxidant roles by inhibiting the mitogen-activated protein kinase (MAPK) pathway and translocation of nuclear transcriptional factor-κB (NF-κB) from the cytosol to the nucleus. These results demonstrate a potential role of PPARγ in protecting muscle fibers against oxidative stress caused by excessive acute exercise due to its anti-inflammatory and anti-oxidant activity exerted by inhibition of the MAPK/NF-κB pathway.
authors.affiliation: Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, 634-18, Deokjin-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-712, South Korea.|Department of Sports Science, College of Natural Science, Chonbuk National University, Jeonju, South Korea.
authors.forename: Jeong-Seok
authors.initials: JS
authors.lastname: Kim
authors.affiliation: Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, 634-18, Deokjin-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-712, South Korea.
authors.forename: Young-Hee
authors.initials: YH
authors.lastname: Lee
authors.affiliation: Department of Physical Education, Jeonju National University of Education, Jeonju, South Korea.
authors.forename: Yong-Uoo
authors.initials: YU
authors.lastname: Chang
authors.affiliation: Department of Oral Biochemistry, Institute of Oral Bioscience, School of Dentistry, Chonbuk National University, 634-18, Deokjin-dong, Deokjin-gu, Jeonju, Jeonbuk, 561-712, South Korea. yihokn@chonbuk.ac.kr.
authors.forename: Ho-Keun
authors.initials: HK
authors.lastname: Yi
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000818:Animals; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000819:agonists / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020778:Matrix Metalloproteinase 2 / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D009043:Motor Activity; D018482:Muscle, Skeletal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009220:Myositis / Q000139:chemically induced / Q000209:etiology / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects; D047495:PPAR gamma / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D005082:Physical Exertion; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D016328:NF-kappa B; D016877:Oxidants; D047495:PPAR gamma; C000613696:PPAR gamma, rat; D011994:Recombinant Proteins; D051546:Cyclooxygenase 2; D020778:Matrix Metalloproteinase 2
keywords: Acute exercise; Cox-2; Il-1β; Inflammatory molecules; MMP-2; TNF-α