title: Vitamin E deficiency sensitizes alveolar type II cells for apoptosis.
abstract: Pre-term neonates and neonates in general exhibit physiological vitamin E deficiency and are at increased risk for the development of acute lung diseases. Apoptosis is a major cause of acute lung damage in alveolar type II cells. In this paper, we evaluated the hypothesis that vitamin E deficiency predisposes alveolar type II cells to apoptosis. Therefore, we measured markers of apoptosis in alveolar type II cells isolated from control rats, vitamin E deficient rats and deficient rats that were re-fed a vitamin E-enriched diet. Bax and cytosolic cytochrome c increased, and the mitochondrial transmembrane potential and Hsp25 expression was reduced in vitamin E deficiency. Furthermore, increased DNA-fragmentation and numbers of early and late apoptotic cells were seen, but caspases 3 and 8 activities and expression of Fas, Bcl-2, Bcl-x and p53 remained unchanged. Vitamin E depletion did not change the GSH/GSSG ratio and the activities of antioxidant enzymes. Thus, vitamin E deficiency may induce a reversible pro-apoptotic response in lung cells and sensitise them for additional insult. In agreement with this hypothesis, we demonstrate that in vivo hyperoxia alone does not induce apoptosis in type II cells of control rats but reversibly increases DNA-fragmentation and numbers of early apoptotic type II cells in vitamin E-depleted cells.
authors.affiliation: Institute of Laboratory Medicine and Pathobiochemistry, University Hospital Charité, Humboldt University of Berlin, Schumannstr. 20/21, Germany.
authors.forename: Pranav
authors.initials: P
authors.lastname: Sinha
authors.forename: Ingrid
authors.initials: I
authors.lastname: Kolleck
authors.forename: Hans Dieter
authors.initials: HD
authors.lastname: Volk
authors.forename: Michael
authors.initials: M
authors.lastname: Schlame
authors.forename: Bernd
authors.initials: B
authors.lastname: Rüstow
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D015153:Blotting, Western; D005434:Flow Cytometry; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006868:Hydrolysis; D009363:Neoplasm Proteins / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014810:Vitamin E / Q000494:pharmacology; D014811:Vitamin E Deficiency / Q000473:pathology*
chemical_list: D000975:Antioxidants; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D014810:Vitamin E; D011065:Poly(ADP-ribose) Polymerases; D010100:Oxygen