Sub-Areas to Calcium Homeostasis:
(Journal Article): Proteomic Identification and Immunolocalization of Increased Renal Calbindin-D28k Expression in OVE26 Diabetic Mice
Thongboonkerd V, Zheng S, McLeish KR, Epstein PN, Klein JB (Core Proteomics Laboratory, Kidney Disease Program, Department of Medicine, University of Louisville, Louisville, KY, USA,
thongboonkerd(at)dr.com
)
IN:
Rev Diabetic Stud
2005; 2(1):19-26
Impact Factor(s) of Rev Diabetic Stud: 0.125 (2006)
ABSTRACT: Diabetic nephropathy is a common diabetic complication that is associated with alterations in the expression of several renal proteins and abnormal calcium homeostasis. We performed proteomic analysis to screen for global changes of renal protein expression in diabetic kidney. Proteins extracted from the whole kidney of 120-day-old OVE26 (a transgenic model of Type 1 diabetes) and FVB (non-diabetic background strain) mice were separated by two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and visualized by SYPRO Ruby staining (n = 5 in each group). Quantitative intensity analysis revealed 41 differentially expressed proteins, of which 30 were identified by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) followed by peptide mass fingerprinting. One of the altered proteins with the greatest magnitude of change was the calcium-binding protein, calbindin-D28k, whose expression was increased 6.7-fold in diabetic kidney. We confirmed the increase in calbindin-D28k expression in diabetic kidney by Western blot analysis. Immunohistochemical study demonstrated that calbindin-D28k expression was markedly increased in tubular epithelial cells of distal convoluted tubules (DCT), collecting ducts (CD), and proximal convoluted tubules (PCT) in diabetic kidney. Calbindin-D28k plays a critical role in maintaining calcium homeostasis. The elevation in renal calbindin-D28k expression in our model may indicate a compensatory mechanism to overcome hypercalciuria in diabetes.
TYPE OF PUBLICATION: Original article
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(Journal Article): Exact and Monte Carlo resampling procedures for the Wilcoxon-Mann-Whitney and Kruskal-Wallis tests.
Berry KJ, Mielke PW, Jr (Department of Sociology, Colorado State University, Fort Collins 80523-1784, USA.,
berry@lamar.colostate.edu
)
IN:
Percept Mot Skills
2000; 91:749-754
ABSTRACT: Exact and Monte Carlo resampling FORTRAN programs are described for the Wilcoxon-Mann-Whitney rank sum test and the Kruskal-Wallis one-way analysis of variance for ranks test. The program algorithms compensate for tied values and do not depend on asymptotic approximations for probability values, unlike most algorithms contained in PC-based statistical software packages.
TYPE OF PUBLICATION: Original article
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(Journal Article): The role of calbindin and 1,25dihydroxyvitamin D3 in the kidney.
Sooy K, Kohut J, Christakos S (Department of Biochemistry and Molecular Biology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark 07103, USA.)
IN:
Curr Opin Nephrol Hypertens
2000; 9(4):341-347
Impact Factor(s) of Curr Opin Nephrol Hypertens: 3.209 (2004), 3.976 (2003), 3.088 (2002), 2.489 (2001)
ABSTRACT: The identification of a putative apical Ca++ channel in 1,25dihydroxyvitamin D3 responsive epithelia (proximal intestine and the distal nephron) as well as recent studies using calbindin-D28k knock-out mice indicating the first direct in-vivo evidence for a role for this calcium-binding protein in renal calcium absorption suggest mechanisms, which had remained incomplete, related to the control of renal calcium absorption.
TYPE OF PUBLICATION: Original article
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(Journal Article): Calbindin-D28K facilitates cytosolic calcium diffusion without interfering with calcium signaling.
Koster HP, Hartog A, van Os CH, Bindels RJ (Department of Cell Physiology, University of Nijmegen, The Netherlands.)
IN:
Cell Calcium
1995; 18(3):187-196
Impact Factor(s) of Cell Calcium: 2.781 (2003), 3.287 (2002), 3.071 (2001)
Fulltext: HTML
ABSTRACT: The role of calbindin-D28K, in transcellular Ca2+ transport and Ca2+ signaling in rabbit cortical collecting system was investigated. Rabbit kidney connecting tubules and cortical collecting ducts, hereafter referred to as cortical collecting system, were isolated by immunodissection and cultured to confluence on permeable filters and glass coverslips. Calbindin-D28K was present in the cytosol of principal cells, but was absent from the intercalated cells. 1,25(OH)2D3 (48 h, 10(-7) M) significantly increased cellular calbindin-D28K levels (194 +/- 15%) and stimulated transcellular Ca2+ transport (41 +/- 3%). This stimulatory effect could be fully mimicked by the endogenous Ca2+ chelator, BAPTA (30 microM BAPTA/AM), which suggests that the presence of Ca2+ chelators alone is sufficient to enhance transcellular Ca2+ transport. Stimulation of Ca2+ transport was not accompanied by a rise in [Ca2+]i. Isosmotic replacement of extracellular Na+ ([Na+]o) for N-methylglucamine (NMG) generated oscillations in [Ca2+]i in individual cells of the monolayer. The functional parameters of these oscillations such as frequency of spiking, resting [Ca2+]i, increase in [Ca2+]i and percentage of responding cells, were not affected by the level of calbindin-D28K. In contrast, loading the cells with BAPTA abruptly stopped these [Ca2+]i oscillations. This suggests that the kinetics of Ca2+ binding by calbindin-D28K are slow relative to the initiation of the [Ca2+]i rise, so that calbindin-D28K, unlike BAPTA, is unable to reduce [Ca2+]i rapidly enough to prevent the initiation of Ca(2+)-induced Ca2+ release.
TYPE OF PUBLICATION: Original article
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(Journal Article): Inhibition of calbindin-D28K expression by cyclosporin A in rat kidney: the possible pathogenesis of cyclosporin A-induced hypercalciuria.
Yang CW, Kim J, Kim YH, Cha JH, Mim SY, Kim YO, Shin YS, Kim YS, Bang BK (Department of Internal Medicine, Kangnam St. Mary's Hospital, Catholic University Medical College of Korea, Seoul.)
IN:
J Am Soc Nephrol
1998; 9:1416-1426
Impact Factor(s) of J Am Soc Nephrol: 6.644 (2004), 7.499 (2003), 6.337 (2001)
ABSTRACT: A recent study by Steiner et al. (Biochem Pharmacol 51: 253-258, 1996) demonstrated a decreased calbindin D28K expression in the kidneys of cyclosporin A (CsA)-treated rats. To evaluate the association of renal calcium handling with calbindin D28K expression in CsA-treated rats, two separate experiments (vehicle [VH] versus CsA groups, 1,25-dihydroxyvitamin D3 [VitD] versus VitD + CsA groups) were done simultaneously. CsA (25 mg/kg per d, subcutaneously) and VitD (0.5 microg/kg per d, subcutaneously) were given for 7 d. The CsA group showed decreased serum calcium, increased urine calcium excretion, and decreased calbindin D28K protein level and immunoreactivity compared with the VH group. The VitD + CsA treatment decreased serum calcium, increased urine calcium excretion, and decreased calbindin D28K protein level and immunoreactivity compared with the VitD alone. CsA treatment did not affect the serum parathyroid hormone and VitD levels. This study demonstrates an association of calbindin D28K expression with the urinary calcium excretion in CsA-treated rats, and suggests that decreased calbindin D28K expression may play a role in renal calcium wasting.
TYPE OF PUBLICATION: Original article
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(Journal Article): Evidence for the impairment of the vitamin D activation pathway by cyclosporine A.
Grenet O, Bobadilla M, Chibout SD, Steiner S (Preclinical Safety, Novartis Pharma AG, Basel, Switzerland.,
olivier.grenet@pharma.novartis.com
)
IN:
Biochem Pharmacol
2000; 59(3):267-272
Impact Factor(s) of Biochem Pharmacol: 3.436 (2004), 2.993 (2003), 3.542 (2002), 3.34 (2001)
ABSTRACT: Cyclosporine A (CsA) is a potent immunosuppressant with the drawback of renal side effects. We reported that CsA markedly decreases calcium-binding protein calbindin-D28k mRNA levels in rat kidneys, and showed that this decrease is associated with its adverse renal effects. The transcription of the calbindin-D28k gene is activated via the vitamin D pathway. In this work, the potential CsA-mediated impairment of the vitamin D pathway was investigated. Wistar rats were treated for 12 days with 50 mg/kg/day CsA or for 20 days with 50 mg/kg/day of the non-immunosuppressant and non-nephrotoxic SDZ PSC 833, which had been previously shown not to affect calbindin-D28k mRNA levels. The expression of the three vitamin D-regulated genes calbindin-D28k, 1,25-dihydroxyvitamin D3-24-hydroxylase (24-OHase), and vitamin D receptor (VDR) were quantified in rat kidney homogenates by real-time reverse transcription-polymerase chain reaction. Plasma parathyroid hormone (PTH) as well as plasma and kidney 1,25 dihydroxyvitamin D3 (calcitriol) levels were monitored in all animals. CsA induced a 85% decrease in calbindin-D28k mRNA levels as well as a 40% and 69% decrease in VDR and 24-OHase mRNA levels, respectively. Plasma and kidney 1,25 dihydroxyvitamin D3 as well as plasma PTH levels were increased by CsA, but not by SDZ PSC 833. The treatment with SDZ PSC 833 did not affect calbindin-D28k or VDR expression, but did cause a 73% decrease in 24-OHase mRNA levels. Taken together, these results indicate an association between CsA-mediated down-regulation of rat renal calbindin-D28k mRNA and the decrease in other 1,25 dihydroxyvitamin D3-regulated genes, suggesting an impairment of the vitamin D pathway by CsA which may be related to its adverse renal side effects and its immunosuppressive activity.
TYPE OF PUBLICATION: Original article
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(Journal Article): Critical role of calbindin-D28k in calcium homeostasis revealed by mice lacking both vitamin D receptor and calbindin-D28k.
Zheng W, Xie Y, Li G, Kong J, Feng JQ, Li YC (Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.)
IN:
J Biol Chem
2004; 279(50):52406-52413
Impact Factor(s) of J Biol Chem: 6.355 (2004), 6.482 (2003), 7.258 (2001)
ABSTRACT: Calbindin (CaBP)-D28k and CaBP-D9k are cytosolic vitamin D-dependent calcium-binding proteins long thought to play an important role in transepithelial calcium transport. However, recent genetic studies suggest that CaBP-D28k is not essential for calcium metabolism. Genetic ablation of this gene in mice leads to no calcemic abnormalities. Genetic inactivation of the vitamin D receptor (VDR) gene leads to hypocalcemia, secondary hyperparathyroidism, rickets, and osteomalacia, accompanied by 90% reduction in renal CaBP-D9k expression but little change in CaBP-D28k. To address whether the role of CaBP-D28k in calcium homeostasis is compensated by CaBP-D9k, we generated VDR/CaBP-D28k double knockout (KO) mice, which expressed no CaBP-D28k and only 10% of CaBP-D9k in the kidney. On a regular diet, the double KO mice were more growth-retarded and 42% smaller in body weight than VDRKO mice and died prematurely at 2.5-3 months of age. Compared with VDRKO mice, the double KO mice had higher urinary calcium excretion and developed more severe secondary hyperparathyroidism and rachitic skeletal phenotype, which were manifested by larger parathyroid glands, higher serum parathyroid hormone levels, much lower bone mineral density, and more distorted growth plate with more osteoid formation in the trabecular region. On high calcium, high lactose diet, blood-ionized calcium levels were normalized in both VDRKO and the double KO mice; however, in contrast to VDRKO mice, the skeletal abnormalities were not completely corrected in the double KO mice. These results directly demonstrate that CaBP-D28k plays a critical role in maintaining calcium homeostasis and skeletal mineralization and suggest that its calcemic role can be mostly compensated by CaBP-D9k.
TYPE OF PUBLICATION: Original article
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