DEVELOPMENTAL EXPRESSION OF SARCOMERIC AND UBIQUITOUS MITOCHONDRIAL CREATINE-KINASE IS TISSUE-SPECIFIC

Creatine kinase (CK) isoenzymes play prominent roles in myocardial ene rgy metabolism. Two nuclear genes encode mitochondrial creatine kinase (MtCK), are tissue-specific in their expression, and are thus designa ted as sarcomeric MtCK (sMtCK) and ubiquitous MtCK (uMtCK). Quantitati ve analysis of the mRNA expression of both MtCKs in developing rat tis sues demonstrates tissue-specific developmental regulation, sMtCK mRNA in heart is undetectable prenatally but is dramatically upregulated b y 28 d postnatally. sMtCK mRNA in skeletal muscle is also extremely lo w prenatally but is markedly upregulated at birth and doubles by 28 d postnatally. uMtCK mRNA expression is present at low levels in fetal b rain and intestine. Brain uMtCK mRNA continues to rise from -4 d prena tally until 28 d postnatally (6-fold increase), but intestinal uMtCK m RNA increases immediately prior to birth, falls, and is upregulated ag ain at 28 d (20-fold). uMtCK mRNA is undetectable in fetal skeletal mu scle or heart, but increases to low levels in skeletal muscle at birth and remains at this level into adulthood. uMtCK is not detectable in heart, lung, testes, or liver at any stage examined. We conclude that sMtCK and uMtCK are developmentally regulated in a tissue-specific man ner. Unlike cytosolic muscle CK and brain CK, there is no isoenzyme sw itch between sMtCK and uMtCK in the developing animal. Our results sug gest that specific trans-acting factors regulate the different develop mental and tissue-specific expression of the MtCK genes.