Renal Calbindin Research Articles

Impact of deoxynivalenol in a calcium depletion and repletion nutritional strategy in piglets.

This study evaluated the effect of dietary calcium (Ca) levels and deoxynivalenol (DON) contamination on Ca and phosphorus (P) utilization and bone mineralization in piglets. During an initial 13-d depletion phase, 64 piglets (15.7 ± 0.7kg) received a control (DON-) or DON-contaminated treatment (DON+, 2.7mg DON/kg) with either a low Ca (Ca-, 0.39%) or normal Ca level (Ca+, 0.65%) with a constant digestible P level (0.40%). A second group of 16 piglets received DON- or DON+ treatments for 9 d for gene expression analysis. During the subsequent 14-d repletion phase, all piglets were fed a Ca+ DON- diet containing 0.65% Ca and 0.35% digestible P without DON. After 5 d of the depletion phase, the absorption of P (DON × Ca; P < 0.05) and Ca was increased by the Ca- (P < 0.01) and DON+ (P < 0.01) diet. After 13 d, feed conversion ratio (P < 0.01) and average daily feed intake (P = 0.06) tended to decrease with the Ca- diet. The bone mineral content (BMC) gain was decreased by Ca, especially with Ca- DON + (DON × Ca, P < 0.05). The P absorption was increased by Ca- DON + (DON × Ca, P < 0.01), although the P retention efficiency was only increased by Ca+ DON + (DON × Ca, P < 0.001). The absorption of Ca was increased by DON+ (P < 0.001), and the Ca efficiency was increased by Ca- DON- (DON × Ca, P < 0.01). After 9 d, the gene expression of intestinal claudin 12 (P < 0.01) and CYP24A1 (P < 0.05), femur cortical RANKL (P < 0.05) and OPG (P = 0.06), and renal calbindin D9K (P < 0.05) and Klotho (P = 0.07) were decreased by DON+. The Ca (P = 0.06) and magnesium (P < 0.01) concentrations were decreased by DON+, and the Ca (P = 0.06) and P digestibility (P < 0.01) were increased. After the repletion phase, Ca- piglets recovered their BMC deficit, but not those receiving DON+ (DON × Ca; P = 0.06). The Ca (P < 0.05) and P (P = 0.06) retention efficiency tended to increase with Ca-. The absorption of Ca and P was increased by Ca- and DON+ (DON × Ca, P < 0.05). The results show that piglets increased their Ca and P utilization efficiency, allowing them to recover the BMC deficit caused by Ca-, but not when the piglets were exposed to DON. Pigs previously receiving Ca-deficient diet with DON still have lower body Ca and P, leading to elevated calcitriol concentrations and enhanced Ca and P intestinal absorption. The fact that DON decreased the expression of genes implicated in Ca intestinal and renal transport and P excretion after 9 d can potentially explain the reduced plasma Ca concentration.

Regulation of renal calbindin expression during cisplatin-induced kidney injury.

Since the discovery of calbindin release into the urine during renal injury, there has been growing interest in the utility of this protein as a biomarker of nephrotoxicity. However, little is known about the intrarenal regulation of the release and expression of this calcium-regulating protein during kidney injury. We sought to characterize the time-dependent expression and excretion of the protein calbindin in the distal tubule in comparison to kidney injury molecule-1 (Kim-1), a protein in the proximal tubule, in mice treated with cisplatin. Urine, blood, and kidneys were collected from male C57BL/6 mice treated with vehicle or cisplatin (20 mg/kgip). Urinary concentrations of calbindin and Kim-1 were elevated by 11.6-fold and 2.5-fold, respectively, within 2 days after cisplatin. Circulating creatinine and blood urea nitrogen levels increased in cisplatin-treated mice by 3 days, confirming the development of acute kidney injury. Time-dependent decreases in intrarenal calbindin protein were observed on Days 3 and 4 and a 200-fold upregulation of calbindin (CALB1) and KIM-1 messenger RNAs(mRNAs) was observed on Day 3. These data suggest that early loss of calbindin protein into the urine along with declines in renal calbindin levels initiates a compensatory induction of mRNA expression at later time points (Days 3 and 4). Understanding the regulation of calbindin during cisplatin nephrotoxicity further enhances its utility as a potential urinary biomarker of kidney damage. The results of the current study support the combined use of a proximal (Kim-1) and distal tubule (calbindin) marker to phenotype acute kidney injury secondary to cisplatin administration.

Decreased urinary calbindin 1 levels in proteinuric rats and humans with distal nephron segment injuries

Several proteins have been proposed as new urinary biomarkers of kidney injuries, but they are not always capable of identifying the kidney nephron segment that has been injured. Since calbindin 1 protein is exclusively localized in the kidney distal nephron segment, it is presumed that its expression is altered during distal nephron segment injuries, resulting in changes in its urinary excretion. Calbindin 1 expression in normal rat kidneys was compared with that in the kidneys of rats that had suffered distal nephron segment injuries (unilateral ureteral obstruction [UUO] or anti-glomerular basement membrane glomerulonephritis [anti-GBM GN]) using immunohistochemical examinations and real-time polymerase chain reaction. The urinary calbindin 1 protein concentration of normal rats was also compared with that of anti-GBM GN rats and of cisplatin nephropathy rats using Western blotting. We also compared the kidney and urinary calbindin 1 protein concentrations of normal human subjects with those of proteinuric patients [immunoglobulin (Ig)A nephropathy; IgAN] with distal nephron segment injuries. Calbindin 1 mRNA expression in the renal cortices and calbindin 1 protein expression in the kidney distal nephron segments were decreased in the UUO and anti-GBM GN rat kidneys. The urinary calbindin 1 protein levels of the anti-GBM GN rats were also markedly decreased, whereas those of the cisplatin nephropathy rats were slightly decreased. The human IgAN patients displayed decreased renal calbindin 1 protein expression in their dilated distal tubules, and some patients displayed decreased urinary calbindin 1 levels. Since it has been demonstrated that decreased urinary calbindin 1 levels are indicative of decreased calbindin 1 kidney expression due to distal nephron segment injuries, calbindin 1 might be a useful urinary biomarker for identifying distal nephron segment injuries.

Soy isoflavones increase bone mineral density without altering markers of whole body vitamin D or calcium metabolism in mice

The soy isoflavone genistein enhances the biological activity of the vitamin D (VD) metabolite 1,25 dihydroxyvitamin D (1,25D) in cultured cells by inhibiting CYP24‐mediated degradation of the hormone. We examined if similar effects can be recapitulated in vivo to improve calcium and bone metabolism. Weanling male B6D2F1 mice were fed AIN‐93G diets containing 50 or 400 IU VD with, or without, Novasoy® 400 soy isoflavone concentrate (added to provide 250 mg genistein/kg diet) until 13 weeks of age. Bone mineral density (BMD) was measured by DEXA. Serum VD metabolites were measured by RIA. Gene expression in duodenum and kidney was measured by RT‐PCR. Higher dietary VD intake increased serum 25 hydroxyvitamin D (25D) from levels viewed as adequate (61 ± 6 nM) to optimal (164 ± 10 nM) for human health but this had no impact on either BMD or molecular indices of calcium metabolism. In contrast, isoflavones increased both serum 25D and femur BMD by 15% (p &lt; 0.01). However, neither serum 1,25D nor tissue gene expression (e.g. duodenal calbindin D9K, TRPV6; renal calbindin D9K or D28K, TRPV5) was influenced by isoflavones. Our data show that the beneficial effect of soy isoflavones on bone that we observed is independent of their ability to modulate whole body VD or calcium metabolism and suggest a direct effect of isoflavones on bone formation or turnover. We thank ADM for Novasoy® 400. Funding: Purdue‐UAB Botanicals Center Pilot Grant.Grant Funding Source: Purdue‐UAB Botanicals Center Pilot Grant

Differential Regulation of Calbindin in the Calcium-Transporting Organs of Birds with High Calcium Requirements

The present review focuses on the differential regulation and differential expression, as well as the possible differential functionality, of avian calbindin-D28k in the three major calcium-transporting tissues: intestine, eggshell gland (ESG) and kidney. Special emphasis is given to their relationships with fast growth and with the laying of long clutches, i.e., unbroken sequences of eggs, separated by one or more days, as affected by the three major regulators, cholecalciferol (vitamin D3), gonadal activity, and intra- or extracellular calcium or its fluxes. The accumulated evidence suggests that intestinal calbindin mostly depends on vitamin D3, ESG calbindin appears to depend on calcium-transport-related factor (s) and to lesser extent also on gonadal activity; whereas renal calbindin partly depends on vitamin D3 and extracellular calcium.

Calbindin-D28k Is Expressed in Osteoblastic Cells and Suppresses Their Apoptosis by Inhibiting Caspase-3 Activity

The rate of osteoblast apoptosis is a critical determinant of the rate of bone formation. Because the calcium-binding protein calbindin-D(28k) has anti-apoptotic properties in neuronal cells and lymphocytes, we searched for the presence of this protein in osteoblastic cells and investigated whether it can modify their response to proapoptotic signals. Calbindin-D(28K) was expressed at low levels in several osteoblastic cell lines and at high levels in primary cultures of murine osteoblastic cells. Transient transfection of rat calbindin-D(28k) cDNA blocked tumor necrosis factor alpha (TNFalpha)-induced apoptosis in osteoblastic MC3T3-E1 cells, as determined by cell viability and nuclear morphology of cells cotransfected with the green fluorescent protein targeted to the nucleus, whereas transfection of the empty vector had no effect. Calbindin-D(28k) levels in several stably transfected MC3T3-E1 lines were directly related to protection from TNFalpha-induced apoptosis. Purified rat calbindin-D(28k) markedly reduced the activity of caspase-3, a critical molecule for the degradation phase of apoptosis, in a cell-free assay. In addition, cell extracts from MC3T3-E1 cells expressing high levels of calbindin-D(28k) decreased caspase-3 activity, compared with extracts from vector-transfected cells. This effect was apparently unrelated to the calcium binding properties of calbindin, as chelation of calcium by EGTA or addition of other calcium-binding proteins such as calbindin-D(9k), S100, calmodulin, and osteocalcin, did not affect caspase-3 activity. Last, calbindin-D(28k) interacts with the active form of caspase-3 as demonstrated by a GST pull-down assay. These results demonstrate that calbindin-D(28k) is a biosynthetic product of osteoblasts with a role in the regulation of apoptosis. They also reveal that the antiapoptotic properties of calbindin-D(28k) may result not only from calcium buffering but also from the ability of the protein to interact with and to inhibit caspase-3 activity, a property that is independent of its calcium binding capability.

New insights into cyclosporine A nephrotoxicity by proteome analysis.

Using two-dimensional gel electrophoresis (2-DE), we recently discovered an association between decreased calcium-binding protein, calbindin-D 28 kDa, urinary calcium wasting and intratubular corticomedullary calcifications in rat kidney. This observation prompted us to investigate kidney tissues of other species, including man. In this paper we show that in dogs and monkeys, which are generally devoid of cyclosporine A (CsA)-mediated nephrotoxicity, renal calbindin levels were not affected by the CsA treatment whereas in CsA-treated human kidney-transplant recipients with renal vascular or tubular toxicity, a marked decrease in renal calbindin-D 28 kDa protein level was found in most of the kidney biopsy sections. The present results strongly suggest that calbindin is a marker for CsA-nephrotoxicity. The discovery of calbindin-D 28 kDa being involved in CsA toxicity has evolved from the application of 2-DE and has not been reported previously, proving that proteomics can provide essential information in mechanistic toxicology. Considering the current improvements in proteome methods it is expected that high throughput proteomics will become an indispensable tool in preclinical safety testing.

Hyperresponsiveness of vitamin D receptor gene expression to 1,25-dihydroxyvitamin D3. A new characteristic of genetic hypercalciuric stone-forming rats.

Hypercalciuria in genetic hypercalciuric stone-forming (GHS) rats is accompanied by intestinal Ca hyperabsorption with normal serum 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] levels, elevation of intestinal, kidney, and bone vitamin D receptor (VDR) content, and greater 1,25(OH)2D3-induced bone resorption in vitro. To test the hypothesis that hyperresponsiveness of VDR gene expression to 1,25(OH)2D3 may mediate these observations, male GHS and wild-type Sprague- Dawley normocalciuric control rats were fed a normal Ca diet (0.6% Ca) and received a single intraperitoneal injection of either 1,25(OH)2D3 (10-200 ng/100 g body wt) or vehicle. Total RNAs were isolated from both duodenum and kidney cortex, and the VDR and calbindin mRNA levels were determined by Northern blot hybridization using specific cDNA probes. Under basal conditions, VDR mRNA levels in GHS rats were lower in duodenum and higher in kidney compared with wild-type controls. Administration of 1,25(OH)2D3 increased VDR gene expression significantly in GHS but not normocalciuric animals, in a time- and dose-dependent manner. In vivo half-life of VDR mRNA was similar in GHS and control rats in both duodenum and kidney, and was prolonged significantly (from 4-5 to > 8 h) by 1,25(OH)2D3 administration. Neither inhibition of gene transcription by actinomycin D nor inhibition of de novo protein synthesis with cycloheximide blocked the upregulation of VDR gene expression stimulated by 1,25(OH)2D3 administration. No alteration or mutation was detected in the sequence of duodenal VDR mRNA from GHS rats compared with wild-type animals. Furthermore, 1,25(OH)2D3 administration also led to an increase in duodenal and renal calbindin mRNA levels in GHS rats, whereas they were either suppressed or unchanged in wild-type animals. The results suggest that GHS rats hyperrespond to minimal doses of 1,25(OH)2D3 by an upregulation of VDR gene expression. This hyperresponsiveness of GHS rats to 1,25(OH)2D3 (a) occurs through an increase in VDR mRNA stability without involving alteration in gene transcription, de novo protein synthesis, or mRNA sequence; and (b) is likely of functional significance, and affects VDR-responsive genes in 1, 25(OH)2D3 target tissues. This unique characteristic suggests that GHS rats may be susceptible to minimal fluctuations in serum 1, 25(OH)2D3, resulting in increased VDR and VDR-responsive events, which in turn may pathologically amplify the actions of 1,25(OH)2D3 on Ca metabolism that thus contribute to the hypercalciuria and stone formation.

Capacity of 1,25-Dihydroxyvitamin D to Stimulate Expression of Calbindin D Changes with Age in the Rat

Studies in rats and humans have shown that there is an age-related decline in the stimulation of intestinal Ca transport by 1,25-dihydroxyvitamin D3[1,25(OH)2D], the active metabolite of vitamin D. The calbindins are a family of vitamin D-dependent calcium-binding proteins found in the intestine (calbindin D-9k) and kidney (calbindin D-28k) and are thought to play a role in calcium transport and homeostasis. The purpose of this study was to determine if the capacity of 1,25(OH)2D to stimulate the expression of calbindin protein and mRNA changes with age. Young (2 months), adult (12 months), and old (22 months) male F344 rats were made deficient in 1,25(OH)2D by being fed a strontium-containing diet and then being given a single ip injection of 1,25(OH)2D. Calbindin protein levels were measured by immunological techniques using specific antisera, and mRNA levels were measured by Northern and dot blots. The maximal amount of calbindin D-9k protein induced by 1,25(OH)2D declined with age in the duodenum but not in the ileum. In time-course studies, there was a delay in calbindin D-9k induction in the duodenum but not in the ileum of adult rats compared to young rats. In contrast to protein induction, maximal calbindin D-9k mRNA levels in response to 1,25(OH)2D were greater in the adult animal and showed no time lag compared to those in the young animal. In the kidney, maximal levels of renal calbindin D-28k protein and mRNA did not change with age, but there was delayed induction in the adult. These studies demonstrate that there is an age-related decrease in the induction of calbindin protein in response to 1,25(OH)2D in the duodenum, but not in the ileum or kidney. This decline may be due to decreased translation of calbindin D-9k mRNA into protein in the duodenum with age.

Estrogen responsiveness of renal calbindin-D28k gene expression in rat kidney.

In women, calcium excretion in the urine rises after menopause and falls with estrogen replacement therapy. The amount of calcium lost in the urine following estrogen therapy is less than should occur based on changes in serum calcium and the amount of calcium filtered by the kidney. This suggests there may be a direct effect of estrogen therapy to increase renal calcium reabsorption. Calbindin D28k is a putative calcium ferry protein located in the distal renal tubules which has been shown to increase transcellular calcium transport. We proposed that estrogen loss after menopause may diminish gene expression of renal calbindin D28k and subsequently diminish renal calcium reabsorption. We used the ovariectomized rat model of estrogen deficiency to investigate changes at the messenger RNA level of calbindin D28k in ovariectomized rats (OVX), sham ovariectomized rats (S-OVX), and estrogen treated ovariectomized rats (E-OVX). We have demonstrated that ovariectomy in rats diminishes the gene expression of renal calbindin D28k. The mRNA levels were approximately three times lower in OVX rats than S-OVX rats. Administration of 17 beta estradiol to OVX rats produced a significant increase in mRNA level to greater than the S-OVX rats by 4 h. Measurement of serum 1,25 dihydroxyvitamin D3 showed lower levels in OVX rats than S-OVX rats but no significant change in E-OVX animals. In conclusion, our results indicate that estrogen increases renal calbindin D28k mRNA levels, by a mechanism independent of changes in 1,25 dihydroxyvitamin D3. This may result in increased expression of calbindin D28k protein which may have a role in reducing renal calcium excretion.

Decrease in kidney calbindin-d 28kda as a possible mechanism mediating cyclosporine A- and FK-506-induced calciuria and tubular mineralization

The use of the immunosuppressant cyclosporine A (CsA) is limited by its adverse renal effects. Most recently, we reported that the drug markedly decreases the levels of the calcium-binding protein calbindin-D 28kDa in kidneys of male Wistar rats. In the present study, the potential relationship between drug-induced nephrotoxicity and the decrease in kidney calbindin-D 28kDa was investigated. Four groups of male Wistar rats were treated for 10 or 31 days with either the immunosuppressant CsA (50 mg/kg/day), FK-506 (5 mg/kg/day), rapamycin (5 mg/kg/day) or with the nonimmunosuppressive cyclosporine derivative 3'keto-[Bmt 1]-[Val 2]-CsA (SDZ PSC-833) (50 mg/kg/day), and the effects on calcium homeostasis, kidney histology and renal calbindin-D 28kDa were examined. Similar effects were found with CsA and FK-506; both drugs strongly reduced kidney calbindin-D 28kDa protein levels, increased urine calcium excretion, caused intratubular calcification, and induced basophilic tubules. In contrast, rapamycin and SDZ PSC-833 caused no decrease in renal calbindin-D 28kDa levels, no noticeable alterations in calcium metabolism, and no renal calcification. The results provide evidence for a link between decreased renal calbindin, increased calcium urine excretion, and intratubular kidney calcification. The present data show no correlation between the decrease in renal calbindin and the induction of basophilic tubules; however, it needs to be investigated if these apparently independent kidney effects may have a common origin upstream of calbindin expression.

Induction of calbindin D-28K in Madin-Darby bovine kidney cells by 1,25(OH)2D3

Renal calbindin D-28K is a calcium binding protein, localized to the distal nephron, whose expression is reduced in vitamin D deficiency and increased upon administration of 1,25(OH)2D3, the active form of vitamin D. Investigation into the molecular regulation of renal calbindin D-28K expression has been limited by the lack of an established cell line which expresses calbindin D-28K in a vitamin D responsive manner. In the studies described here, we compared the expression of calbindin D-28K and the vitamin D receptor (VDR) in four renal cell lines: Madin-Darby bovine kidney (MDBK) cells, Madin-Darby canine kidney (MDCK) cells, LLC-PK1 pig kidney cells and opossum kidney (OK) cells. We report that MDBK cells express the highest relative levels of calbindin D-28K and the VDR, and that 1,25(OH)2D3 increases calbindin D-28K expression in these cells. No expression of calbindin D-28K was detected in MDCK, LLC-PK1 or OK cells. Kinetic studies indicated that calbindin D-28K protein increased with time for up to 24 hours after a single dose of 1,25(OH)2D3 (10(-7) M) in MDBK cells. Immunofluorescence studies indicated that in control MDBK cells, the majority of calbindin D-28K was localized in cytosol, with a definite concentration in the peri-nuclear region. In 1,25(OH)2D3 treated cells, calbindin D-28K was enhanced in cytosol and was detected within the nucleus. In contrast to heterogeneous primary culture systems, in which a minority of cells express calbindin D-28K, virtually all MDBK cells expressed calbindin D-28K, even in the absence of 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Dietary Calcium Modifies Concentrations of Lead and Other Metals and Renal Calbindin in Rats

We studied the effects of dietary calcium on kidney, femur, testis, liver, heart and brain concentrations of lead, magnesium, iron, copper, calcium and zinc in rats exposed to lead for 1 y. Renal levels of the 28,000 Da, vitamin D-dependent, calcium-binding protein calbindin-D28K were also measured. Seventy-two weanling male Sprague-Dawley rats were randomly assigned to one of nine treatment groups. Rats were fed diets containing 0.1, 0.5 or 2.5% Ca for 52 wk and were simultaneously given either 0, 50 or 100 mg lead/L in their drinking water. Rats fed the 0.1% Ca diet had organ lead concentrations that were two- to 20-fold greater than the corresponding animals fed 0.5% Ca. Rats fed diets containing 2.5% Ca had the lowest organ lead concentrations. Despite substantial effects of diet Ca on organ lead concentrations, Ca did not significantly influence concentrations of most other divalent metals studied with the exception of kidney calcium and magnesium, testis iron, plasma ionic calcium and magnesium, and several femur metals. Kidney calcium concentrations were lower in rats fed 2.5% Ca diets than in those fed 0.1 or 0.5% Ca diets. For rats not given lead, renal calbindin concentrations were highest in rats fed 0.1% Ca, and lowest in rats fed 2.5% Ca. Lead inhibited an increase in renal calbindin in the rats fed 0.1% Ca, but paradoxically increased renal calbindin levels in animals fed 2.5% Ca.

Modulation of chick intestinal and renal calbindin gene expression by dietary vitamin D 3, 1,25-dihydroxyvitamin D 3, calcium and phosphorus

Synthetic oligonucleotide probes complementary to chick calbindin-28 kDa-mRNA were used to study the latter's regulation and relationship to calbindin in the chick. The effects of vitamin D 3 sources and dietary alteration on the genomic expression were characterized by Northern blot and solution hybridization. Intestinal calbindin and its mRNA were almost absent in vitamin D-deficient chicks and were not affected by dietary alteration. Renal calbindin and its mRNA were lower in the vitamin D-deficient than in vitamin D 3- or 1,25-dihydroxyvitamin D 3 (1,25(OH) 2D 3)-fed chicks. In the same animal, renal calbindin mRNA and calbindin were higher than intestinal. In vitamin D 3-fed chicks, dietary calcium (Ca) or phosphorus (P) restriction induced, and high dietary Ca inhibited, intestinal calbindin and its mRNA synthesis. In the same chicks, dietary P restriction induced renal calbindin mRNA and calbindin synthesis. In 1,25-(OH) 2D 3-fed chicks, dietary P restriction induced and high dietary Ca inhibited the synthesis of intestinal and renal calbindin. The results suggest that: (a) most of the changes in renal and intestinal calbindin could be attributed to the changes in the mRNA; (b) the adaptation to dietary Ca and P alterations requires vitamin D metabolites; (c) high dietary Ca affects intestinal and renal calbindin-mRNA and calbindin via mechanisms independent of kidney 1-hydroxylase; and (d) plasma Ca and renal calbindin or its mRNA tend to change together in vitamin D-deficient or vitamin D 3-fed, but not in 1,25(OH) 2D 3-fed chicks.

Modulation of Rat Calbindin-D28Gene Expression by 1,25-Dihydroxyvitamin D3and Dietary Alteration

We have used a specific cDNA to the mammalian 28,000 Mr vitamin D-dependent calcium binding protein (calbindin-D28k) to study the regulation of the expression of this mRNA in rat kidney and brain. The effects of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) and dietary alteration on genomic expression were characterized by both Northern and slot blot analysis. Administration of 1,25-(OH)2D3 for 7 days (25 ng/day) to vitamin D-deficient rats resulted in a marked increase in renal calbindin-DmRNA, renal calbindin, and serum calcium. When vitamin D-deficient rats were supplemented for 10 days with calcium (3% calcium gluconate in the water, 2% calcium in the diet) serum calcium levels were similar to the levels observed in the 1,25-(OH)2D3-treated rats. However, in the calcium-supplemented rats the levels of renal calbindin and renal calbindin mRNA were similar to the levels observed in the vitamin D-deficient rats, suggesting that calcium alone without vitamin D does not regulate renal calbindin gene expression in vivo. In dietary alteration studies in vitamin D-replete rats, renal calbindin protein and mRNA increased 2.5-fold in rats fed diets low in phosphate providing evidence that in the rat the nutritional induction of calbindin is accompanied by a corresponding alteration in the concentration of its specific mRNA. Under low dietary calcium conditions, the levels of renal calbindin protein and mRNA were similar to the levels observed in control rats, although 1,25-(OH)2D3 serum levels were markedly elevated, suggesting that factors in addition to 1,25-(OH)2D3 can modulate renal calbindin gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D-induced calcium-binding protein: comparative aspects in kidney and intestine

Vitamin D-induced calcium-binding protein: comparative aspects in kidney and intestine