REGULATION OF CREATINE-KINASE ISOENZYMES IN HUMAN PLACENTA DURING EARLY, MID-GESTATION, AND LATE-GESTATION

OBJECTIVE: Creatine kinase (CK) isoenzymes play an important role in c ellular energy transduction. Two isoenzymes of creatine kinase, ubiqui tous mitochondrial creatine kinase (uMtCK) and cytosolic brain creatin e kinase (BCK), are postulated to form the creatine phosphate (CP) shu ttle, in which creatine serves to transport high-energy phosphate from the mitochondria to its site of utilization. Coordinated regulation o f these genes is essential for efficient energy transduction. We exami ned human CK isoenzyme regulation in placentas during all three trimes ters of gestation to define the mRNA and protein expression patterns o f uMtCK and BCK and to test the CP shuttle hypothesis. METHODS: Placen tal samples were collected from a total of 26 patients from the first, second, and third trimesters. Total RNA and protein were prepared fro m each sample and quantified. Quantitative RNA analysis was performed by gel electrophoresis and dot blot techniques using isoenzyme-specifi c human cDNA probes for uMtCK and BCK. Protein expression of uMtCK and BCK was examined by Western blot analysis using isoenzyme-specific an tibodies to uMtCK and BCK. RESULTS: Analysis of RNA demonstrated the c oordinate expression of uMtCK and BCK mRNAs in human placenta, with pe ak expression of both in the term placentas. Western blot analysis dem onstrated coordinate expression of uMtCK and BCK proteins in the first and second trimester, but not in the term placenta. Expression levels of uMtCK and BCK proteins were not consistent with their respective m RNA levels in the term placenta. CONCLUSION: Expression of uMtCK and B CK in human placenta is highly regulated, and post-transcriptional reg ulation of uMtCK and BCK expression occurs in the term placenta. The c oordinate regulation of uMtCk and BCK in human placenta supports the C P shuttle hypothesis. This analysis demonstrates that human placenta h as high energy needs that can change rapidly; thus, a functioning CP s huttle may be important in the maintenance and termination of pregnanc y. Copyright (C) 1996 by the Society for Gynecologic Investigation.