Alkaline phosphatase induction

Hatoff DE, Hardison WG (1981) BUe acids modify alkaline phosphatase induction and... 

Cell metabolism induction. Methanol extract of STE, in collagen-producing cells, stimulated glycolysis by 80% in cartilage but was not affected in the other tissues. Medium alkaline phosphatase activity was unaffected. In the frontal bone and cartilage, [ H]hydroxyproline and [ H]proline contents were decreased. Neither was affected in the aorta. 

Fig. 12.14 Left Structures of mono-substituted alkylpolyamines (AKla-5a), two bri-substituted analogues (AK6b, 7b) were also synthesized and examined for SAR confirmation. Right Inhibition of LPS (100 ng/mL)-induced NF-kB induction in HEK-293 cells stably transfected with Tlr4, MD-2, CD 14, and an NF-icB-secreted alkaline phosphatase reporter gene construct. Polymyxin B was used as the positive control...

Several assays, such as the ultra-sensitive luminescent ELRA developed by Seifert (2004) with a detection limit of 20 ng L-1 for 17 (3-estradiol, have been reported in the literature. Although these assays are simple to use, many factors, such as differences in culture conditions, cell density or cell-line clones, affect the potency of estrogenic substances, and that makes the standardization of these methods difficult. The induction of several proteins or enzyme activities (e.g. the increasing levels of alkaline phosphatase, cathepsin D, prolactin and vitellogenin as a consequence of progestogens) has also been used to study estrogenicity. However, expression of these proteins or enzyme activities is restricted to specific cell lines and cannot be extrapolated to other tissues or species. 

Measurement of serum y-GT activity has clinical significance. The enzyme is present in all tissues, but the highest level is in the kidney however, the serum enzyme originates primarily from the hepatobiliary system. Elevated levels of serum y-GT are found in the following disorders intra- and posthepatic biliary obstruction (elevated serum y-GT indicates cholestasis, as do leucine aminopeptidase, 5 -nucleotidase, and alkaline phosphatase) primary or disseminated neoplasms some pancreatic cancers, especially when associated with hepatobiliary obstruction alcohol-induced liver disease (serum y-GT may be exquisitely sensitive to alcohol-induced liver injury) and some prostatic carcinomas (serum from normal males has 50% higher activity than that of females). Increased activity is also found in patients receiving phenobarbital or phenytoin, possibly due to induction of y-GT in liver cells by these drugs. 

Interesting indeed are the recent studies of Griffin and Cox (G20, G21) on the mechanism of adrenocorticoid induction of alkaline phosphatase in human cell cultures. Two temporal phases in the induction of enzyme in HeLa cells are reported a first 12-hour period exhibiting a slow rise in activity, followed by a sudden marked linear increase extending from 15 to 80 hours. The elevation of activity is marked (around 10-fold). The fact that puromycin blocked induction immediately, and actinomycin D... 

There is sufficient evidence to consider enzyme induction as a process which could explain elevations in tissue (V8) and in serum alkaline phosphatase levels. 

C19. Cox, R. P., and MacLeod, C. M., Hormonal induction of alkaline phosphatase in human cells in tissue cultiue. Nature 190, 85-87 (1961). 

G20. Griffin, M. J., and Cox, R. P., Studies on the mechanism of hormonal induction of alkaline phosphatase in human cell cultures. I. Effects of Puromycin and Actinomycin D. J. Cell Biol. 29, 1-9 (1966). 

N25. Nitowsky, H. M., Herz, F., and Geller, S., Induction of alkaline phosphatase in dispersed cell cultures by changes in osmolarity. Biochem. Biophys. Res. Commun. 12, 293-299 (1963). 

TNAP is expressed in human hepatocytes, and bile acids increase its activity [93] and secretion in the bile [94]. TNAP in rat hepatocytes is predominantly localized in the bile canalicular domain of the plasma membrane [95, 96], but can be addressed to the baso-lateral membrane in the presence of high levels of bile acid [97]. In contrast, mouse hepatocytes do not express TNAP [98]. In humans, liver TNAP may be expressed both at the sinusoidal and biliary pole of the hepatocyte. This explains why a significant proportion of TNAP activity in the circulation of healthy individuals originates from the liver. TNAP serum levels are of major clinical relevance as a marker of cholestasis. AP levels increase due to retrograde reflux of biliary alkaline phosphatase, enhanced hepatic synthesis and enzyme release into the serum, and induction of the intestinal alkaline phosphatase form [94, 99, 100]. 

Gum LR, Kam WK, Byrd LC et al (1987) Effects of sodium butyrate on human colonic adenocarcinoma cells. Induction of placental-Uke alkaline phosphatase. L Biol Chem 262 1092-1097... 

Chou JY, Takahashi S (1987) Control of placental alkaline phosphatase gene expression in HeLa cells induction of synthesis by prednisolone and sodium butyrate. Biochemistry 26 3596-3602... 

Kaplan MM, Righetti A (1970) Induction of rat liver alkaline phosphatase the mechanism of the serum elevation in bile duct obstruction. J Clin Invest 49 508-516... 

Kapojos JJ, Poelstra K, Borghuis T et al (2003) Induction of glomerular alkaline phosphatase after challenge with lipopolysaccharide. Int J Exp Pathol 84 135-144... 

K6. Kaplan, M. M., Induction of rat liver alkaline phosphatase by bile duct ligation. Yale J. Biol. Med. 52, 69-75 (1979). 

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