Nitric oxide synthase type I and type III gene expression are developmentally regulated in rat lung.
The successful transition from fetal to neonatal life involves a marked decline in pulmonary vascular resistance which is modulated in part by endothelium-derived nitric oxide. To define the molecular processes which prepare the pulmonary circulation for nitric oxide mediation of vasodilatation at the time of birth, we determined the ontogeny of endothelial nitric oxide synthase (NOS-III) gene expression in lungs from fetal and newborn rats. Maturational changes in lung neuronal NOS (NOS-I) expression were also investigated; the latter isoform has been localized to rat bronchiolar epithelium. NOS proteins were examined by immunoblot analysis, and mRNA abundance was assessed in reverse transcription-polymerase chain reaction assays. Both NOS-III and NOS-I protein were detectable in 16-day fetal lung, they increased 3.8- and 3.1-fold, respectively, to maximal levels at 20 days of gestation (term = 22 day), and they fell postnatally (1-5 days). In parallel with the findings for NOS-III protein, NOS-III mRNA increased from 16 to 20 days gestation and fell after birth. In contrast, NOS-I mRNA abundance declined during late fetal life and rose postnatally. These findings were confirmed by Northern analyses. Thus NOS-III and NOS-I gene expression are developmentally regulated in rat lung, with maximal NOS-III and NOS-I protein present near term. The regulation of pulmonary NOS-III may primarily involve alterations in transcription or mRNA stability, whereas NOS-I expression in the maturing lung may also be mediated by additional posttranscriptional processes.
North
A J
AJ
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235.
Star
R A
RA
Brannon
T S
TS
Ujiie
K
K
Wells
L B
LB
Lowenstein
C J
CJ
Snyder
S H
SH
Shaul
P W
PW
D000375:Aging / Q000378:metabolism; D000594:Amino Acid Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000254:growth & development / Q000378:metabolism*; D001483:Base Sequence; D005314:Embryonic and Fetal Development; D005333:Fetus / Q000378:metabolism*; D005786:Gene Expression Regulation; D008168:Lung / Q000196:embryology* / Q000201:enzymology* / Q000254:growth & development; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D019001:Nitric Oxide Synthase; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D014158:Transcription, Genetic
D015335:Molecular Probes; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases