Antenatal glucocorticoid therapy accelerates ATP production with creatine kinase increase in the growth-enhanced fetal rat heart.
BACKGROUND
Previous study has demonstrated the increase of several cardiac function-related proteins, including creatine kinase (CK) as an important enzyme in the process of ATP synthesis in the fetal heart of rats administered glucocorticoid (GC) antenatally. In the present study the effect of antenatal GC administration on the CK expression in fetal and neonatal hearts was demonstrated.


RESULTS
Dexamethasone was administered to pregnant rats on days 19 and 20 of gestation. The mRNA levels of the CK isoforms, CK-M and Mi-CK, in 21-day-old fetal and 1-day-old neonatal hearts were significantly increased after antenatal GC administration. CK protein levels were also increased in both cultured cardiomyocytes and the mitochondria of the hearts. Uptake of 5, 5', 6, 6'-tetrachloro-1, 1', 3, 3'-tetraethyl-benzimidazolocarbocyanine iodide by mitochondria was significantly increased. An increased ATP level accompanied the CK increase in the neonatal hearts. Furthermore, in vitro these effects were mediated though the GC receptor of cardiomyocytes. Peroxisome proliferator-activated receptor gamma as the upstream transcription factor of CK was significantly increased in fetal hearts.


CONCLUSIONS
These results suggest that antenatal GC administration accelerates ATP synthesis through increased CK and may contribute to maturation of the premature heart so that it is ready for preterm delivery. (Circ J 2010; 74: 171 - 180).
Mizuno
Masanori
M
Department of Pediatrics, St Marianna University School of Medicine, Japan. m2.water-field@marianna-u.ac.jp
Takeba
Yuko
Y
Matsumoto
Naoki
N
Tsuzuki
Yoshimitsu
Y
Asoh
Kentaro
K
Takagi
Masayuki
M
Kobayashi
Shinichi
S
Yamamoto
Hitoshi
H
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D052279:Creatine Kinase, MB Form / Q000378:metabolism*; D003907:Dexamethasone / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000196:embryology*; D015735:Mifepristone / Q000494:pharmacology; D023421:Models, Animal; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors
D005938:Glucocorticoids; D047495:PPAR gamma; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D015735:Mifepristone; D003907:Dexamethasone; D000255:Adenosine Triphosphate; D052279:Creatine Kinase, MB Form