Am. J. Respir. Cell Mol. Biol., Vol 11, No. 3, 09 1994, 366-371.
Manganese superoxide dismutase expression in alveolar type II epithelial cells from nonventilated and hypoperfused lungs
WJ Russell, S Matalon and RM Jackson
Birmingham VA Medical Center, Alabama.
Lungs that have been hypoxic and hypoperfused because of atelectasis and
the resulting decrease in pulmonary arterial blood flow develop specific
decreases in manganese superoxide dismutase (MnSOD) activity and are
sensitive to oxidant injury during reoxygenation. Since the MnSOD protein
is concentrated in mitochondria of alveolar epithelial type II cells
(ATII), we hypothesized that expression of MnSOD would be decreased in
these cells also as a result of hypoxia. To investigate whether regulation
of MnSOD expression occurred before or after transcription, we determined
whether MnSOD protein content or steady- state mRNA level changed after
hypoxia as well. ATII cells were isolated by elastase digestion from lungs
of adult rabbits after right lungs had been hypoxic and hypoperfused for 7
days because of unilateral atelectasis. MnSOD activity was measured by
inhibition of cytochrome c reduction in the presence of 1 mM KCN, MnSOD
protein content was measured on immunoblots, and MnSOD mRNA was quantified
on slot blot autoradiograms. MnSOD activity was 8.4 +/- 1.9 U/mg protein in
ATII cells from control lungs and 6.8 +/- 1.5 U/mg protein in ATII cells
from hypoxic and hypoperfused lungs (n = 9, P = 0.037). MnSOD protein
content was 5.1 +/- 1.4 micrograms/mg protein in ATII cells from control
and 4.1 +/- 1.2 micrograms/mg protein in ATII cells from hypoxic and
hypoperfused lungs (P = 0.021). ATII cell MnSOD mRNA/18S ribosomal RNA
(ratio of arbitrary absorbance units) determined by RNA slot blots was 2.18
+/- 1.26 in ATII cells from control lungs and 2.94 +/- 0.88 in ATII cells
from hypoxic lungs (n = 7, P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
