Regulation and properties of bone alkaline phosphatase during vitamin C deficiency in guinea pigs.
The precise physiological role of alkaline phosphatase is unknown, although evidence suggests it is involved in bone mineralization. Previous studies showed that serum and bone alkaline phosphatase activity is decreased during vitamin C deficiency. Some effects of scurvy, such as inhibition of collagen synthesis, are related to weight loss and subsequent induction of insulin-like growth factor binding proteins and they can be duplicated in fasted guinea pigs receiving vitamin C. We found that decreased alkaline phosphatase activity in bone and serum during scurvy was not completely due to the "fasting effect" and that the decrease in serum was due to loss of bone isoenzyme activity. There also was a decrease in immunoreactive enzyme protein and alkaline phosphatase mRNA concentrations in bone of scorbutic animals, indicating that synthesis of the enzyme was inhibited. Sialylation and addition of the glycosylphosphatidylinositol anchor to the enzyme in bone tissue were not affected by scurvy. The concentration of mRNA for osteocalcin, a bone-specific marker, also fell during scurvy and to a much greater extent than either alkaline phosphatase or type I collagen mRNAs, while osteopontin mRNA concentrations increased. These results differ from the reported role of ascorbic acid on the pattern of expression of these proteins during differentiation of osteoblasts in culture. The decreased expression of collagen, alkaline phosphatase, and osteocalcin could explain the defects in bone caused by scurvy.
Mahmoodian
F
F
Laboratory of Biochemistry, National Cancer Institute, Bethesda, Maryland 20892-4255, USA.
Gosiewska
A
A
Peterkofsky
B
B
D000469:Alkaline Phosphatase / Q000378:metabolism*; D000818:Animals; D001842:Bone and Bones / Q000201:enzymology*; D003094:Collagen / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006031:Glycosylation; D006168:Guinea Pigs; D007527:Isoenzymes / Q000378:metabolism; D008099:Liver / Q000201:enzymology; D008970:Molecular Weight; D015675:Osteocalcin / Q000235:genetics; D053495:Osteopontin; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics; D012614:Scurvy / Q000201:enzymology* / Q000235:genetics; D012795:Sialoglycoproteins / Q000235:genetics
D007527:Isoenzymes; D012333:RNA, Messenger; D012795:Sialoglycoproteins; D015675:Osteocalcin; D053495:Osteopontin; D003094:Collagen; D000469:Alkaline Phosphatase