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Reactive oxidant and p42/44 MAP kinase signaling is necessary for mechanical strain-induced proliferation in pulmonary epithelial cells.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Chess, Patricia Rose O'reilly, Michael A. Sachs, Fredrick Finkelstein, Jacob N. |
| Copyright Year | 2005 |
| Abstract | Mechanical strain is necessary for normal lung growth and development. Individuals with respiratory failure are supported with mechanical ventilation, leading to altered lung growth and injury. Understanding signaling pathways initiated by mechanical strain in lung epithelial cells will help guide development of strategies aimed at optimizing strain-induced lung growth while mitigating ventilator-induced lung injury. To study strain-induced proliferative signaling, focusing on the role of reactive oxidant species (ROS) and p42/44 mitogen-activated protein (MAP) kinase, human pulmonary epithelial H441 and MLE15 cells were exposed to equibiaxial cyclic mechanical strain. ROS were increased within 15 min of strain. N-acetylcysteine inactivated strain-induced ROS and inhibited p42/44 MAP kinase phosphorylation and strain-induced proliferation. PD98059 and UO126, p42/44 MAP kinase inhibitors, blocked strain-induced proliferation. To verify the specificity of p42/44 MAP kinase inhibition, cells were transfected with dominant-negative mitogen-activated protein kinase kinase-1 plasmid DNA. Transfected cells did not proliferate in response to mechanical strain. To determine whether strain-induced tyrosine kinase activity is necessary for strain-induced ROS-p42/44 MAP kinase signaling, genistein, a tyrosine kinase inhibitor, was used. Genistein did not block strain-induced ROS production or p42/44 MAP kinase phosphorylation. Gadolinium, a mechanosensitive calcium channel blocker, blocked strain-induced ROS production and p42/44 MAP kinase phosphorylation but not strain-induced tyrosine phosphorylation. These data support ROS production and p42/44 MAP kinase phosphorylation being involved in a common strain-induced signaling pathway, necessary for strain-induced proliferation in pulmonary epithelial cells, with a parallel strain-induced tyrosine kinase pathway. |
| Starting Page | 1639 |
| Ending Page | 1640 |
| Page Count | 2 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://www.sachslab.buffalo.edu/pdf/reactiveoxidantandp.pdf |
| PubMed reference number | 15890751v1 |
| Volume Number | 99 |
| Issue Number | 3 |
| Journal | Journal of applied physiology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acetylcysteine Calcium Channel Blockers Gadolinium Genistein Lung diseases MAP2K1 protein, human Mitogens Oxidants PD 98059 Protein Kinases Protein Tyrosine Kinase Protein-tyrosine kinase inhibitor Respiration Respiratory Insufficiency Structure of parenchyma of lung Tyrosine Phosphorylation U 0126 Ventilator - respiratory equipment eIF-2 Kinase kinase activity lung growth negative regulation of reactive oxygen species biosynthetic process |
| Content Type | Text |
| Resource Type | Article |
