Vitamin D and adaptation to dietary calcium and phosphate deficiencies increase intestinal plasma membrane calcium pump gene expression.

Abstract

The effect of vitamin D and other variables on the synthesis of the chicken intestinal plasma membrane calcium pump (PMCA) mRNA was assesed. The DNA probe for Northern analysis was obtained by reverse transcription and PCR with intestinal poly(A)+ RNA, using two 20-mer oligonucleotide primers homologous to the 3' coding region of the human teratoma PMCA. An EcoRI restriction fragent of the PCR product was cloned into the pBluescript I KS(-) phagemid vector, and the chimeric plasmid was used to transform Escherichia coli. The amino acid sequence deduced from the nucleotide DNA sequence of the PCR product and the cloned DNA were 96% homologous with the teratoma sequence. Northern blots of intestinal poly(A)+ RNA with 32P-labeled DNA showed the presence of three major species of chicken PMCA mRNAs at about 6.6, 5.4, and 4.5 kb. Northern analysis with the chicken PMCA DNA indicated that repletion of vitamin D-deficient chickens with vitamin D increased PMCA mRNAs in the duodenum, jejunum, ileum, and colon. After injection of 1,25-dihydroxyvitamin D3 intravenously into vitamin D-deflcient chickens, duodenal PMCA mRNA tended to increase by 2 hr, reached a maximum at about 16 hr, and returned to baseline levels at 48 hr. Adaptation of chickens to either a calcium-or phosphorus-deficient diet resulted in a 2-to 3-fold increase in duodenal PMCA mRNA. These results indicate that vitamin D and specific variables that affect calcium absorption through the vitamin D-endocrine system increase intestinal PMCA gene expression.A major factor controlling the efficiency of calcium absorption is the vitamin D hormone, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (1, 2). 1,25(OH)2D3 elicits both genomic (3) and nongenomic (4-10) effects on the intestinal cell. Among the former effects are the induction of the synthesis of intestinal calbindin-D9k in mammalian species and intestinal calbindin-D28k in avian species (3). In addition, we recently demonstrated another apparent genomic response, a vitamin D-dependent increase in the amount ofcalcium pump units in the basolateral membrane of the avian enterocyte (11). This finding is consistent with previous observations (12)(13)(14)(15)(16) showing that repletion of vitamin D-deficient animals with vitamin D or 1,25(OH)2D3 results in an enhancement of the ATP-dependent uptake of Ca2+ by isolated basolateral membrane vesicles. Further, animals fed diets deficient in calcium or phosphorus adapt to these deficiencies by an increase in the synthesis of 1,25(0H)2D3 (17)(18)(19)(20)(21), resulting in an increase in the efficiency of calcium and phosphorus absorption. These adaptations are associated with an increased synthesis of calbindin-D and its mRNA (17)(18)(19)(20)(22)(23)(24)(25)(26)(27)(28)

Association between Vitamin D Receptor Gene Polymorphism and Alzheimer's Disease

“…Supporting results implying a reduction in the VDR mRNA levels in the CA1 and CA2 pyramidal cells of hippocampus in AD patients have been shown (Sutherland et al 1992). Vitamin D deficiency and/or VDR polymorphisms, which may decrease the affinity of VDR to vitamin D (Cai et al 1993;Bouillon et al 1998), may affect detoxification mechanisms, calcium homeostasis and expression of neurotrophins. This may lead to neuronal aging, neuronal damage and neurodegeneration via other genomic and environmental factors.…”

“…On the other hand, calcium homeostasis affects many cellular mechanisms, especially neurotransmission. Vitamin D was found to alter calcium uptake in some excitable cells by modulating the L-type voltage sensitive calcium channels in hippocampus and by inducing the synthesis of calcium binding proteins (Cai et al 1993;Landfield et al 1998;Garcion et al 2002).…”

TRPV6 is not required for 1α,25-dihydroxyvitamin D 3 -induced intestinal calcium absorption in vivo

“…Schachter and colleagues (9) also found a transporter responsive to vitamin D. Others have reported that vitamin D stimulates the basal lateral membrane calcium ATPase believed to be a calcium transporter (10,11). These components have been put together in a diagrammatic fashion to present the current hypothesis of how 1,25-(OH) 2 D 3 stimulates active intestinal calcium absorption.…”

Involvement of the transepithelial calcium transport disruption and the formation of epididymal stones in roosters

“…The transepithelial calcium reabsorption depends on proteins that mediate the apical calcium entry within the cell, named TRPV5 and TRPV6 (transient receptor potential vanilloid channel), the diffusion of the ion throughout the cytoplasm bound to calcium-binding proteins (CaBP), such as CaBP-D9K or CaBP-D28K, and its extrusion to the extracellular environment in the basolateral membranes of the cells by the Na C /Ca 2C exchanger (NCX) or the plasma membrane calmodulin-dependent calcium ATPase (PMCA; Bindels et al 1991, Van Baal et al 1996, Hoenderop et al 2002, 2005, Bar 2009). This process is orchestrated by several hormones that regulate the expression and activity of the aforementioned proteins, including vitamin D3, androgens, and estrogens (Cai et al 1993, Hoenderop et al 2001, 2005, Van Abel et al 2002, Dick et al 2003, Meyer et al 2007, Oz et al 2007, Suzuki et al 2008, Hsu et al 2010, Yang et al 2011. Interestingly, the efferent ductules of roosters express high levels of vitamin D3 receptor (VDR), androgen receptor (AR), and estrogen receptors (ESR1 and ESR2 -also known as ERa and ERb respectively; Kwon et al 1997, Dornas et al 2007, 2008, Oliveira et al 2011a.…”