Journalartikel
Autorenliste: Vadasz, Istvan; Dada, Laura A.; Briva, Arturo; Helenius, Iiro Taneli; Sharabi, Kfir; Welch, Lynn C.; Kelly, Aileen M.; Grzesik, Benno A.; Budinger, G. R. Scott; Liu, Jing; Seeger, Werner; Beitel, Greg J.; Gruenbaum, Yosef; Sznajder, Jacob I.
Jahr der Veröffentlichung: 2012
Zeitschrift: PLoS ONE
Bandnummer: 7
Heftnummer: 10
ISSN: 1932-6203
Open Access Status: Gold
DOI Link: https://doi.org/10.1371/journal.pone.0046696
Verlag: Public Library of Science
Abstract:
Elevated CO2 levels (hypercapnia) occur in patients with respiratory diseases and impair alveolar epithelial integrity, in part, by inhibiting Na,K-ATPase function. Here, we examined the role of c-Jun N-terminal kinase (JNK) in CO2 signaling in mammalian alveolar epithelial cells as well as in diptera, nematodes and rodent lungs. In alveolar epithelial cells, elevated CO2 levels rapidly induced activation of JNK leading to downregulation of Na, K-ATPase and alveolar epithelial dysfunction. Hypercapnia-induced activation of JNK required AMP-activated protein kinase (AMPK) and protein kinase C-zeta leading to subsequent phosphorylation of JNK at Ser-129. Importantly, elevated CO2 levels also caused a rapid and prominent activation of JNK in Drosophila S2 cells and in C. elegans. Paralleling the results with mammalian epithelial cells, RNAi against Drosophila JNK fully prevented CO2-induced downregulation of Na, K-ATPase in Drosophila S2 cells. The importance and specificity of JNK CO2 signaling was additionally demonstrated by the ability of mutations in the C. elegans JNK homologs, jnk-1 and kgb-2 to partially rescue the hypercapnia-induced fertility defects but not the pharyngeal pumping defects. Together, these data provide evidence that deleterious effects of hypercapnia are mediated by JNK which plays an evolutionary conserved, specific role in CO2 signaling in mammals, diptera and nematodes.
Zitierstile
Harvard-Zitierstil: Vadasz, I., Dada, L., Briva, A., Helenius, I., Sharabi, K., Welch, L., et al. (2012) Evolutionary Conserved Role of c-Jun-N-Terminal Kinase in CO2-Induced Epithelial Dysfunction, PLoS ONE, 7(10), Article e46696. https://doi.org/10.1371/journal.pone.0046696
APA-Zitierstil: Vadasz, I., Dada, L., Briva, A., Helenius, I., Sharabi, K., Welch, L., Kelly, A., Grzesik, B., Budinger, G., Liu, J., Seeger, W., Beitel, G., Gruenbaum, Y., & Sznajder, J. (2012). Evolutionary Conserved Role of c-Jun-N-Terminal Kinase in CO2-Induced Epithelial Dysfunction. PLoS ONE. 7(10), Article e46696. https://doi.org/10.1371/journal.pone.0046696
Schlagwörter
ALPHA-SUBUNIT; ALVEOLAR FLUID REABSORPTION; CARBON-DIOXIDE AVOIDANCE; ELEVATED CO2 LEVELS; INDUCED ENDOCYTOSIS; JNK ACTIVATION; KAPPA-B
