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Mechanism of retinoic acid and mitogen-activated protein kinases regulating hyperoxia lung injury
- Source :
- Journal of Huazhong University of Science and Technology [Medical Sciences]. 26:178-181
- Publication Year :
- 2006
- Publisher :
- Springer Science and Business Media LLC, 2006.
-
Abstract
- To investigate the protective effect of retinoic acid (RA) on hyperoxic lung injury and the role of RA as a modulator on mitogen-activated protein kinases (MAPKs), gastation 21 d Sprague-Dawley (SD) fetuses (term = 22 d) were delivered by hysterotomy. Within 12-24 h of birth, premature rat pups were randomly divided into 4 groups (n=12 each): air-exposed control group (group I); hyperoxia-exposed group (group II), air-exposed plus RA group (group III), hyperoxia-exposed plus RA group (group IV). Group I, III were kept in room air, and group II, IV were placed in 85 % oxygen. The pups in groups III and IV were intraperitoneally injected with RA (500 microg/kg every day). All lung tissues of premature rat pups were collected at the 4th day after birth. Terminal transferase d-UTP nick end labeling (TUNEL) staining was used for the detection of cell apoptosis. The expression of PCNA was immunohistochemically detected. Western blot analysis was employed for the determination of phosphorylated and total nonphosphorylated ERKs, JNKs or p38. Our results showed that lungs from the pups exposed to hyperoxia for 4 d exhibited TUNEL-positive nuclei increased markedly throughout the parenchyma (P0.01), and decreased significantly after RA treatment (P0.01). The index of PCNA-positive cells was significantly decreased (P0.01), and was significantly increased by RA treatment (P0.01). The air-space size was significantly enlarged, secondary crests were markedly decreased in hyperoxia-exposed animals. RA treatment improved lung air spaces and secondary crests in air-exposed pups, but had no effect on hyperoxia-exposure pups. Western blotting showed that the amounts of JNK, p38 and ERK proteins in hyperoxia-exposure or RA-treated lung tissues were same as those in untreated lung tissues (P0.05), whereas activation of these MAPKs was markedly altered by hyperoxia and RA. After hyperoxia exposure, p-ERK1/2, p-JNK1/2 and p-p38 were dramatically increased (P0.01), whereas p-JNK1/2 and p-p38 were markedly declined and p-ERK1/2 was further elevated by RA treatment (P0.01). It is concluded that RA could decrease cell apoptosis and stimulate cell proliferation under hyperoxic condition. The protection of RA on hyperoxia-induced lung injury was related to the regulation of MAP kinase activation.
- Subjects :
- p38 mitogen-activated protein kinases
Biomedical Engineering
Retinoic acid
Apoptosis
Tretinoin
Biology
Lung injury
Biochemistry
Rats, Sprague-Dawley
Biomaterials
Andrology
chemistry.chemical_compound
In Situ Nick-End Labeling
Genetics
medicine
Animals
Hypoxia
Lung
Cells, Cultured
Earth-Surface Processes
Hyperoxia
Respiratory Distress Syndrome
TUNEL assay
Kinase
Rats
Enzyme Activation
Animals, Newborn
Terminal deoxynucleotidyl transferase
chemistry
Mitogen-activated protein kinase
Immunology
biology.protein
Female
Mitogen-Activated Protein Kinases
medicine.symptom
Subjects
Details
- ISSN :
- 19931352 and 16720733
- Volume :
- 26
- Database :
- OpenAIRE
- Journal :
- Journal of Huazhong University of Science and Technology [Medical Sciences]
- Accession number :
- edsair.doi.dedup.....d213301d2aa654ad68416547fdd92cea