Reduced alkaline phosphatase activity in diabetic rat bone: a re-evaluation.
We found previously that human bone alkaline phosphatase (AP) was glycated by aseptic incubation with glucose, and partially broken down by reactive oxygen species. In this study, we examined whether selective in vivo glycation of AP molecules occurred in bone tissue, using experimental diabetic rats induced by streptozotocin and spontaneously diabetic rats. Additionally, the effects of hyperlipidemia on bone AP activity were examined. Serum AP activity was significantly elevated after incipient onset of diabetes, and the increased activity originated from the intestinal isozyme. High levels of intestinal AP activity were also observed in rats with hyperlipidemia induced by feeding high-fat or high-fructose chow, but the AP activity in bone tissues was maintained at a constant level. AP activity in bone was reduced after the onset of diabetes. The resulting bone AP molecule bound to an aminophenylboronic acid column, which had affinity for glycated proteins, and contained smaller molecular sizes than the native bone AP. These results suggest that elevated levels of serum AP activity originated from the intestinal isozyme accompanied with hyperlipidemia induced by diabetes. In contrast, the reduced serum levels of AP activity in diabetic rats might be dependent on inactivation of bone AP, which was glycated, followed by partial breakdown of bone AP molecules, possibly due to reactive oxygen species.
Koyama
I
I
Department of Medical Technology, Junior College, Saitama Medical School, Saitama Medical School, Japan. koyamaw@saitama-med.ac.jp
Yakushijin
M
M
Nakajima
T
T
Hokari
S
S
Kawai
S
S
Oh-Ie
K
K
Inoue
I
I
Negishi
K
K
Katayama
S
S
Komoda
T
T
D000469:Alkaline Phosphatase / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001842:Bone and Bones / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000201:enzymology*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000201:enzymology*; D006031:Glycosylation; D006801:Humans; D006949:Hyperlipidemias / Q000150:complications / Q000201:enzymology; D007422:Intestines / Q000201:enzymology; D007527:Isoenzymes / Q000737:chemistry / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D009924:Organ Culture Techniques; D051381:Rats; D011913:Rats, Inbred BB; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D014018:Tissue Distribution