Disease relevance of ALPI

• Human colon cancer Caco-2 cells were transiently transfected with Cdx1 and/or Cdx2, and semiquantitative RT-PCR was used to study the effects on IAP mRNA expression [1].
• The ALPI Trial: the Italian/European experience with adjuvant chemotherapy in resectable non-small lung cancer [2].
• During a 17-month period a pilot study of the value of urinary enzyme measurements (IAP and tissue non-specific alkaline phosphatase--TNAP, using monoclonal antibody-based immunoassays, and N-acetyl-beta-glucosaminidase--NAG, using colorimetric assay) in 50 prospectively followed cases of acute renal failure (ARF) was performed [3].
• The baculovirus IAP gene (inhibitor of apoptosis), which blocks tumor necrosis factor (TNF)-induced apoptosis, protects several fibroblast cell types from apoptosis, suggesting the TNF pathway is important for FB(1)-induced apoptosis [4].
• In contrast, IAP and retrovirus type C were rarely found in beta-cells from the control group [5].

Psychiatry related information on ALPI

• CONCLUSIONS: Chronic alcohol consumption causes increased intestinal GGT and IAP activity in man [6].

High impact information on ALPI

• Moreover, overexpression of PTEN, which antagonizes PI3K, significantly augmented the induction of IAP enzyme activity in HT29 and Caco-2 cells treated with sodium butyrate and in spontaneously differentiated Caco-2 cells [7].
• Brush-border enzyme (intestinal alkaline phosphatase [IAP] and sucrase) activities, IAP messenger RNA levels, and IAP promoter induction were measured [7].
• Indeed, the membrane-anchored IAP Ig variable domain suffices to mediate Vn particle binding in this system, while the multiply membrane-spanning and cytoplasmic domains are dispensable [8].
• To better determine the function of IAP, we have characterized and used an IAP-deficient human cell line [8].
• These data demonstrate that some alpha v integrin ligand-binding functions are IAP independent, whereas others require IAP, presumably through direct physical interaction between its Ig domain and the integrin [8].

Chemical compound and disease context of ALPI

• When the islets of NON mice were incubated with or without IL-1 (10 U/ml) in the presence of high glucose, IAP was rarely found in beta-cells and retrovirus type C was undetectable in beta-cells [5].

Biological context of ALPI

• Furthermore, from a comparison of our data with the linkage map of the syntenic region on mouse chromosome 1, we conclude that the t(2;13) breakpoint is most closely flanked by loci INHA and ALPI within this map interval [9].
• Transient transfections with IAP-luciferase reporter constructs were used to characterize the mechanisms by which KLF4 activates IAP transcription [10].
• IAP transactivation by KLF4 is likely mediated through a critical region located within the proximal IAP promoter region [10].
• Transfections with a variety of IAP-luciferase reporter constructs were used to identify a Cdx response element located within the human IAP gene promoter [1].
• This sensitization to TNF-alpha-induced killing was attributable to suppression of IAP (inhibitors of apoptosis) production known to be regulated by the cytoprotective nuclear factor-kappaB-dependent arm of TNF-alpha signaling [11].

Anatomical context of ALPI

• To identify new putative promoter motifs responsible for the regulation of ALPI expression during differentiation of the enterocytes, we have conducted a computer-assisted cis-element search of the proximal human ALPI promoter sequence [12].
• The intestinal alkaline phosphatase gene (ALPI) encodes a digestive brush-border enzyme, which is highly upregulated during small intestinal epithelial cell differentiation [12].
• The ability of HNF-4alpha to stimulate the expression from the ALPI promoter was investigated in the nonintestinal Hela cell line [12].
• Transient transfection studies with luciferase reporter plasmids carrying various internal and 5' deletion mutations of the IAP promoter localized a putative thyroid hormone response element (TRE) to a region approximately 620 nucleotides upstream (-620) of the ATG start codon [13].
• The highest IAP levels were found in 2 yolk-sac tumors [14].

Associations of ALPI with chemical compounds

• This dramatic loss of IAP expression from tumor stroma/vasculature may form a strong basis for explaining amifostine selectivity [15].
• In contrast, the abundance of IAP expression in normal tissues, stromal and vascular, ensures an intense hydrolysis of WR-2721 and rapid intracellular accumulation of WR-1065 [15].
• The thyroid hormone receptor complex and KLF4 synergistically activate the enterocyte differentiation marker gene IAP, suggesting a previously unrecognized interrelationship between these two transcription factor pathways [16].
• Concomitant treatment with T3 and butyric acid produced an additive effect on IAP transactivation [17].
• To evaluate a possible quantitative relationship between the rise in intestinal alkaline phosphatase (IAP) activity and triglyceride-rich lipoproteins in the blood after an oral fat intake, a specific and sensitive immunocatalytic assay was used [18].

Other interactions of ALPI

• There are at least three alkaline phosphatase (AP) isoenzymes in man: a heat-stable placental enzyme (PLAP), a less heat-stable intestinal form (IAP), and the very heat-labile AP enriched in liver, bone and kidney [19].
• We used fluorescence in situ hybridization (FISH) to map ALPI (intestinal alkaline phosphatase) to 2q36.3-q37.1 and FN1 to 2q34 [20].
• Functional analysis revealed that Cdx1 transactivates (fourfold, P < 0.05) the IAP promoter through a novel Cdx response element (GTTTAGA) located between -2369 and -2375 upstream of the translational start site [1].
• To define the structural differences between these isozymes, we have built models of the TNAP, IAP, and GCAP molecules based on the 1.8-structure of PLAP(1) and have performed a comparative structural analysis [21].
• Median enzyme concentration were increased in 'poor' compared to 'good' prognosis patients: start IAP 3.2 versus 2.2 U/g creat (NS), start NAG 48.6 versus 13.7 (P < 0.01), start TNAP 3.5 versus 0.9 (P < 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)[3]

Analytical, diagnostic and therapeutic context of ALPI

• Northern blotting detected expression of two IAP transcripts, which were increased approximately 3-fold in response to T3 [13].
• Confocal microscopy confirms the colocalization of IAP and the ligand for cubilin, intrinsic factor [22].
• The results of RT-PCR, quantitative real-time PCR, and Western blot analyses showed that ZBP-89 was expressed at low levels in Caco-2 and HT-29 cells, whereas IAP was minimally expressed and absent in these cells, respectively [23].
• EMSA and chromatin immunoprecipitation (ChIP) were performed to examine the binding of ZBP-89 to the IAP promoter [23].
• IAP did not float with lipoproteins on ultracentrifugation of plasma, nor did IAP bind to lipid droplets from a fat emulsion added to plasma.(ABSTRACT TRUNCATED AT 250 WORDS)[18]

References