Disease relevance of Ihpk1

• The objective of this study was to determine whether InsP6 has similar anti-neoplastic effect on other tumor models, such as murine fibrosarcoma [1].
• We have previously reported that phytic acid (inositol hexaphosphate or InsP6), a natural constituent of cereal diet, when administered in drinking water exerts a consistent antitumor effect on experimental colon cancer in vivo [1].

High impact information on Ihpk1

• Inositol hexaphosphate (InsP6) is the most abundant inositol phosphate found in plants [2].
• In this study, we investigated the influence of InsP6 on tumor promoter-induced cell transformation and signal transduction pathways leading to activator protein 1 activation, which is considered to play a crucial role in tumor promotion [2].
• Antisense oligonucleotides directed against specific PKC isoforms (alpha, beta II, delta, epsilon, xi) revealed the involvement of PKC-epsilon in InsP6-induced exocytosis [3].
• These data demonstrate that PKC-epsilon is involved in InsP6-induced exocytosis in pancreatic beta-cells [3].
• In the presence of inhibitors of the protein phosphatase calcineurin to block endocytosis, intracellular application of InsP6 produced a dose-dependent stimulation of exocytosis, and half-maximal effect was observed at 22 microM [3].

Biological context of Ihpk1

• Because Ins(1,4,5)P3 3-kinase-transfected cells grew less rapidly than vector-transfected controls, we determined whether the synthesis of InsP5 and InsP6 was related to a specific phase of the cell cycle [4].
• Since InsP6 is known to be a chelator of divalent cations, in preparation for putative clinical trials in humans, we also looked at the mineral bioavailability [5].
• In addition to reduce cell proliferation, InsP6 increases differentiation of malignant cells often resulting in reversion to the normal phenotype [6].
• InsP6 also blocked UVB-induced phosphorylation of IkappaB-alpha, which is known to result in the inhibition of NF-kappaB transcriptional activity [7].
• Although it is well-accepted that the phosphatidylinositol signalling transduction pathway, producing inositol-1,4,5-P3 (InsP3) and inositol-1,3,4,5-P4 (InsP4) as second messengers, functions in heart muscle, virtually nothing is known about the roles of the higher inositol polyphosphates such as inositolhexakisphosphate (InsP6) [8].

Anatomical context of Ihpk1

• Inositolhexakisphosphate (InsP6) plays a pivotal role in the pancreatic beta-cell stimulus-secretion coupling [3].
• Mass measurements of InsP5 and InsP6 revealed no significant difference between kinase- and vector-transfected fibroblasts [4].
• These findings indicate that the PLP-specific domain confers the InsP6 binding activity and this interaction may be important for directing PLP transport to central nervous system myelin [9].
• When 1-50 microM Al3+ was present, InsP6 became a less effective inhibitor of Ins(1,3,4,5)P4 3-phosphatase activity; this effect did not depend on the presence of cellular membranes, contrary to a previous proposal [10].
• The latter phenomenon largely explains how, in a cell-free system where Ins(1,3,4,5)P4 3-phosphatase is inhibited by endogenous InsP6, the addition of Al3+ can apparently increase the enzyme activity [10].

Associations of Ihpk1 with chemical compounds

• In recent studies, we have demonstrated that inositol hexaphosphate (InsP6) inhibits experimental colon carcinogenesis [11].
• Two weeks following the beginning of InsP6 supplementation, rats were given six injections of azoxymethane (AOM) at a dose of 8 mg/kg body wt/week and were killed 30 weeks following the last injection [5].
• CCh, high K+, and PGE1 also caused accumulations of [3H]inositol 1,4,5-trisphosphate [Ins(1,4,5)P3], [3H]inositol 1,3,4,6-tetrakisphosphate [Ins(1,3,4,6)P4], and [3H]inositol hexakisphosphate (InsP6) [12].
• We have revealed that several proteins, including alpha adaptins which are specific subunits of clathrin assembly protein, AP2, were eluted from mouse brain by affinity elution chromatography from the C2 domains of Syt II-immobilized Sepharose using 50 microM of InsP6 [13].
• Fractionation of SR and SL membranes on sucrose density gradients, after solubilization with CHAPS, indicated that InsP6 bound to two separate protein peaks in both these membranes, while InsP4 bound to only one [8].

Physical interactions of Ihpk1

• However, under the isotonic condition, PLP binds inositol hexakisphosphate (InsP6) significantly, not inositol 1,3,4,5-tetrakisphosphate [9].

Regulatory relationships of Ihpk1

• In the present study, we demonstrated that inositolhexakisphosphate (InsP6) inhibits basic FGF (bFGF) binding to heparin [14].

Other interactions of Ihpk1

• Inositolhexakisphosphate (InsP6): an antagonist of fibroblast growth factor receptor binding and activity [14].
• Most of the InsP6-binding proteins are involved in vesicular transport, suggesting the involvement of PLP in vesicular transport [9].

Analytical, diagnostic and therapeutic context of Ihpk1

• We report that intraperitoneal injection of InsP6 reduces growth of subcutaneously transplanted fibrosarcoma (FSA-1) in mice, prolongs survival of tumor-bearing mice and reduces the number of pulmonary metastases [1].

References