Transgenic expression of cyclooxygenase-2 (COX2) causes premature aging phenotypes in mice
| Autor: | Vivek Vaish, Kevin Field, Joohwee Kim, Minsub Shim, Ioulia Chatzistamou, Mingxiao Feng |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Genetically modified mouse Premature aging Gene isoform Aging Transgene p16 Mice Transgenic macromolecular substances Biology Pathogenesis Histones 03 medical and health sciences Mice 0302 clinical medicine Animals TP53 Phosphorylation premature aging food and beverages Aging Premature Cell Biology Lipid signaling Fibroblasts beta-Galactosidase Phenotype Cell biology 030104 developmental biology Cyclooxygenase 2 030220 oncology & carcinogenesis biology.protein Cyclooxygenase prostaglandin COX2 Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Cyclooxygenase (COX) is a key enzyme in the biosynthesis of prostanoids, lipid signaling molecules that regulate various physiological processes. COX2, one of the isoforms of COX, is highly inducible in response to a wide variety of cellular and environmental stresses. Increased COX2 expression is thought to play a role in the pathogenesis of many age-related diseases. COX2 expression is also reported to be increased in the tissues of aged humans and mice, which suggests the involvement of COX2 in the aging process. However, it is not clear whether the increased COX2 expression is causal to or a result of aging. We have now addressed this question by creating an inducible COX2 transgenic mouse model. Here we show that post-natal expression of COX2 led to a panel of aging-related phenotypes. The expression of p16, p53, and phospho-H2AX was increased in the tissues of COX2 transgenic mice. Additionally, adult mouse lung fibroblasts from COX2 transgenic mice exhibited increased expression of the senescence-associated β-galactosidase. Our study reveals that the increased COX2 expression has an impact on the aging process and suggests that modulation of COX2 and its downstream signaling may be an approach for intervention of age-related disorders. |
| Databáze: | OpenAIRE |
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