Phosphate depletion enhances tissue-nonspecific alkaline phosphatase gene expression in a cultured mouse marrow stromal cell line ST2

Alkaline phosphatases (ALP) are highly ubiquitous enzymes present in the ma jority of animals from bacteria to higher vertebrate. Although their wide d istribution in nature has suggested that these enzymes should perform impor tant biological functions, their detailed roles or natural substrates remai n unknown. In Escherichia coli, the extracellular phosphate (Pi) limitation induces the ALP gene, indicating the role of extracellular Pi in ALP gene regulation. However, little is known about the similar mechanisms in mammal ian cells. This study was designed to examine the effect of low Pi medium o n the ALP activity and its expression in the mouse stromal cell line ST2. T he enzymatic property was classified into tissue-nonspecific ALP (TNSALP). After treatment by Pi starvation for 3 days, there was a a-fold increase in the specific activity of TNSALP. RT-PCR analysis revealed that the mRNA of the TNSALP gene was highly stimulated. These results indicated that the ef fect of Pi depletion on ALP activity was regulated at the TNSALP transcript ional level, suggesting that the possible role of the Pi sensing system for biological functions of ALP might have been conserved in evolution. Our fi ndings also made it possible to discuss the physiological roles of ALP, in vivo. (C) 1999 Academic Press.