Disease relevance of Cabp1

• A single 1,25-(OH)2D3 injection (650 pmol/100 g of body weight) induced a 2-fold increase in Mr 9000 CaBP gene transcription within 15 min in the duodenum of vitamin D-deficient rats [1].
• The contribution of endogenous Ca2+ buffers to the kinetics of inactivation was investigated by comparing currents recorded from control cells to currents recorded from neurons that have lost a specific Ca(2+)-binding protein, Calbindin-D28K (CaBP), after kindling-induced epilepsy [2].
• In this study we have directly examined the role of CaBP in these processes by (1) recombinantly overexpressing CaBP in an inducible manner and (2) downregulating CaBP expression using antisense technology, using the rat choriocarcinoma cell line Rcho-1 as a trophoblastic cell model system [3].
• We used herpes simplex amplicons to overexpress calbindin D(28k) (CaBP) selectively in dentate gyrus (DG) granule cells [4].
• OBJECTIVE: To clarify the role of calcium-binding proteins (CaBP) in hypertension [5].

Psychiatry related information on Cabp1

• CaBP immunoreactivity in LSO neurons is only transiently present, suggesting a critical period in development during which the control of Ca2+ homeostasis in LSO neurons may be of particular importance [6].
• Peak response times parallel those found with CaBP biosynthesis, i.e., 3 h in cells from vitamin D-replete animals fed diet III, 7 h in cells from vitamin D-replete animals fed diet I, and 12 h in cells from vitamin D-deficient animal [7].

High impact information on Cabp1

• Treatment of duodenal tissue from rats deficient in vitamin D with 1,25-dihydroxy-vitamin D3 [1,25-(OH)2-D3] led to more than a doubling of calcium uptake by the isolated cells and the appearacne in those cells of previously undetectable calcium-binding protein (CaBP) [8].
• CaBP1 binds to the CaM-binding domain, co-immunoprecipitates with alpha12.1 from transfected cells and brain extracts, and colocalizes with alpha12.1 in discrete microdomains of neurons in the hippocampus and cerebellum [9].
• CaBP/caldendrin, a subfamily of the EF-hand-containing neuronal calcium sensor family of calmodulin-related proteins, bind specifically to the InsP(3)-binding region of all three InsP(3)R channel isoforms with high affinity (K(a) approximately 25 nM) in a Ca(2+)-dependent manner (K(a) approximately 1 microM) [10].
• CaBP is also localized to a portion of dopaminergic and a few nondopaminergic neurons in the substantia nigra pars compacta and in most dopaminergic neurons in the ventral tegmental area [11].
• The distinct distributions of CaBP and parvalbumin in the basal ganglia are discussed in terms of their possible roles as intracellular calcium buffer systems related to the physiologic response properties of the neurons in which they are contained [11].

Chemical compound and disease context of Cabp1

• It was concluded, based upon these experiments, that cadmium retention and signs of toxicity are enhanced by feeding low Ca diet and that the increased CaBP activity due to Ca restrictions is responsible for the increased Cd uptake observed [12].
• Kainate-induced epileptic seizures induce a recruitment of caldendrin to the postsynaptic density in rat brain [13].
• Diazepam treatment of fully kindled rats was effective in blocking generalized motor seizures without causing any restoration of the depleted levels of CaBP [14].
• Induction of motor seizures with pentylenetetrazol had no effect upon hippocampal CaBP levels [14].
• Hypercalcemia and hyperphosphatemia was accompanied by increased CaBP activity and reduced weight gain in the vitamin D3 group as well as in the vitamin D3 ester group [15].

Biological context of Cabp1

• Our studies indicate that, whereas 1,25-(OH)2D3 does not regulate 28-kDa CaBP mRNA levels in the brain, the hormone modulates 28-kDa CaBP gene expression in intestine and kidney in a tissue-specific manner, by acting through both transcriptional and post-transcriptional mechanisms [16].
• A study of the thermal stability indicated that renal CaBP is heat-stable up to 75 degrees C. Binding studies utilizing the technique of equilibrium dialysis established a dissociation constant of 2.1 X 10(-6) M and binding sites with a capacity of approximately 4 mol Ca2+/mol of CaBP [17].
• Conversely, downregulation of CaBP expression had a negative effect on calcium uptake, calcium transport, and trophoblast differentiation in Rcho-1 cells [3].
• Duodenal calcium absorption and calcium binding protein (CaBP) are depressed in uncontrolled experimental (alloxan and streptozotocin) diabeties in the rat [18].
• These experiments provide a functional correlate for CaBP and suggest that it may have a significant role in Ca2+ homeostasis and the determination of selective neuronal vulnerability [19].

Anatomical context of Cabp1

• The neuron-specific Ca2+-binding protein caldendrin: gene structure, splice isoforms, and expression in the rat central nervous system [20].
• Caldendrin immunoreactivity (IR) is tightly associated with the cortical cytoskeleton, enriched in the postsynaptic density (PSD) fraction, and associates late during development with the synaptic cytomatrix [20].
• The expression is highly heterogenous within cortex, with highest levels of caldendrin IR in layer III of the piriform and layer II/III of the somatosensory cortex [20].
• Association of Caldendrin splice isoforms with secretory vesicles in neurohypophyseal axons and the pituitary [21].
• On the other hand, those neurons that project to the patches are selectively lesioned by the neonatal 6-OHDA striatal injections, do not express CaBP, and have dendrites that are directed ventrally into the pars reticulata [22].

Associations of Cabp1 with chemical compounds

• After a single intravenous dose of 500 ng of 1,25-(OH)2D3, intestinal 28-kDa CaBP mRNA levels were increased 50-fold, kidney levels were increased 4-fold, and cerebellum levels were unchanged [16].
• Pretreatment of vitamin D-deficient chicks with actinomycin D had little effect on the acute phase of the 1,25-(OH)2D3 induction of 28-kDa CaBP mRNA in intestine but blunted the induction in kidney [16].
• By contrast, in the kidney, cycloheximide pretreatment resulted in an increased steady-state (vitamin D-deficient) level of 28-kDa CaBP mRNA, but completely abolished the induction of 1,25-(OH)2D3 [16].
• Rat renal CaBP was found to have a pI of 4.8 and showed increased electrophoretic mobility during polyacrylamide gel electrophoresis in the presence of 1 mM EDTA [17].
• In contrast, overexpression of CIB1 or CaBP1 attenuated InsP(3)R-dependent Ca(2+) signaling, and in vitro pre-exposure to CIB1 reduced the number of channels available for subsequent stimulation by InsP(3) [23].

Other interactions of Cabp1

• In contrast to CaBP1, coexpression of VILIP-2 slows inactivation in a Ca2+-independent manner, but this effect also requires myristoylation [24].
• All parvalbumin-containing All amacrines were immunopositive for caldendrin [25].

Analytical, diagnostic and therapeutic context of Cabp1

• In addition the distribution of caldendrin in rat brain has been assessed by immunohistochemistry [20].
• Rat renal CaBP was purified from heat-treated post-mitochondrial supernatants by gel filtration on Sephadex G-100 followed by preparative gel electrophoresis [17].
• Immunologically, using Ouchterlony immunodiffusion, a precipitin line which joined with total coalescence with that due to purified renal CaBP was observed with extracts of rat brain and kidney but not with extracts of rat parathyroid, skeletal muscle, myocardium, bone, pancreas, intestine, and liver [17].
• Circular dichroism studies indicated that the alpha-helical content of renal CaBP was of the order of 31% and was changed to a minor degree by the addition of calcium [17].
• Rats fed a 0.8% strontium diet for 7 days to drive down serum 1,25-dihydroxyvitamin D3 levels [1,25(OH)2D3] and then injected with 300 ng 1,25(OH)2D3/100 body weight had increased duodenal CaBP (2.5-fold) and femur OC mRNA (2.2-fold) 24 h after treatment [26].

References