Leptin Promotes cPLA2 Gene Expression through Activation of the MAPK/NF-κB/p300 Cascade
| Autor: | Wei-Ning Lin, Pei-Sung Hsu, Chi-Sheng Wu, Jia-Feng Chang |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
MAPK/ERK pathway
Leptin Male leptin inflammation MAPK NF-κB p300 Adipose tissue environment and public health lcsh:Chemistry chemistry.chemical_compound Mice lcsh:QH301-705.5 Spectroscopy Regulation of gene expression NF-kappa B General Medicine Computer Science Applications medicine.symptom biological phenomena cell phenomena and immunity Mitogen-Activated Protein Kinases hormones hormone substitutes and hormone antagonists Signal Transduction medicine.medical_specialty endocrine system p38 mitogen-activated protein kinases Inflammation Biology Lung injury Catalysis Article Inorganic Chemistry Internal medicine Cell Line Tumor medicine Animals Humans Physical and Theoretical Chemistry Molecular Biology Group IV Phospholipases A2 Organic Chemistry Enzyme Activation enzymes and coenzymes (carbohydrates) Endocrinology lcsh:Biology (General) lcsh:QD1-999 chemistry Gene Expression Regulation E1A-Associated p300 Protein |
| Zdroj: | International Journal of Molecular Sciences Volume 16 Issue 11 Pages 27640-27658 International Journal of Molecular Sciences, Vol 16, Iss 11, Pp 27640-27658 (2015) International Journal of Molecular Sciences; Volume 16; Issue 11; Pages: 27640-27658 |
| ISSN: | 1422-0067 |
| Popis: | Hyperplasia or hypertrophy of adipose tissues plays a crucial role in obesity, which is accompanied by the release of leptin. Recently, obesity was determined to be associated with various pulmonary diseases including asthma, acute lung injury, and chronic obstructive pulmonary disease. However, how obesity contributes to pulmonary diseases and whether leptin directly regulates lung inflammation remains unclear. We used cell and animal models to study the mechanisms of leptin mediation of pulmonary inflammation. We found that leptin activated de novo synthesis of cytosolic phospholipase A2-α (cPLA2-α) in vitro in the lung alveolar type II cells, A549, and in vivo in ICR mice. Upregulated cPLA2-α protein was attenuated by pretreatment with an OB-R blocking antibody, U0126, SB202190, SP600125, Bay11-7086, garcinol, and p300 siRNA, suggesting roles of p42/p44 MAPK, p38 MAPK, JNK1/2, NF-κB, and p300 in leptin effects. Leptin enhanced the activities of p42/p44 MAPK, p38 MAPK, JNK1/2, and p65 NF-κB in a time-dependent manner. Additional studies have suggested the participation of OB-R, p42/p44 MAPK, and JNK1/2 in leptin-increased p65 phosphorylation. Furthermore, p300 phosphorylation and histone H4 acetylation were reduced by blockage of OB-R, p42/p44 MAPK, p38 MAPK, JNK1/2, and NF-κB in leptin-stimulated cells. Similarly, blockage of the MAPKs/NF-κB/p300 cascade significantly inhibited leptin-mediated cPLA2-α mRNA expression. Our data as a whole showed that leptin contributed to lung cPLA2-α expression through OB-R-dependent activation of the MAPKs/NF-κB/p300 cascade. |
| Databáze: | OpenAIRE |
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