Levels Of calbindin-D Research Articles

Significant elevation of urinary 28-kD calbindin-D and N-acetyl-beta-D-glucosaminidase levels in patients undergoing extracorporeal shock wave lithotripsy.

Calbindin-D, a vitamin D-dependent calcium binding protein with a molecular mass of 28 kD, is found predominantly in distal renal tubules and central nervous system tissues in man. We have developed a highly sensitive enzyme immunoassay for human 28-kD calbindin-D and demonstrated its advantages as a new marker for damage to distal renal tubules. Urinary N-acetyl-beta-D-glucosaminidase (NAG), a lysosomal enzyme of the proximal renal tubules, is another segment-specific indicator of renal damage. To clarify whether both proximal and distal renal tubules are similarly affected by extracorporeal shock wave lithotripsy (SWL) treatment, urinary 28-kD calbindin-D and NAG were measured before, then immediately, 2 and 24 hours after SWL in 17 renal lithiasis patients. Levels of urinary calbindin-D were markedly elevated immediately and 2 hours after SWL and then decreased. In sera, levels of calbindin-D also increased, closely correlated with the changes in urinary values. Levels of urinary NAG were also significantly elevated immediately after SWL and then decreased. The results indicate that damage to both proximal and distal renal tubules occurs simultaneously with SWL and that the two markers can be applied as sensitive indicators of such side effects and their alleviation with protective agents.

Cyclosporine A-induced Decrease in Calbindin-D 28 kDa in Rat Kidney but not in Cerebral Cortex and Cerebellum

Recently, we reported that in rat, cyclosporine A (CsA) markedly decreases the levels of calbindin-D (CABP-D) 28 kDa in kidney. CABP-D 28 kDa is a calcium-binding protein which is highly expressed in calcium-transporting tissues such as kidney or brain. In this study, we investigated whether, in addition to the kidney, CsA also has an effect on CABP-D 28 kDa in rat brain. Three groups of male Wistar rats received 15 mg/kg/day or 50 mg/kg/day of CsA orally for 12 days, whereas controls received vehicle solution for the same period. CABP-D 28-kDa protein and CsA were quantified in homogenates of kidney, cerebral cortex and cerebellum, and the localization of CABP-D 28 kDa was assessed in the different tissue sections by immunohistochemistry. In kidney, CABP-D 28 kDa was strongly and dose dependently decreased, and was located in tubular epithelial cells. In brain, CABP-D 28 kDa was not changed and was mainly located in pyramidal cells of the cortex and in cerebellum exclusively in Purkinje cells. High CsA concentrations were measured in kidney, more than 17-fold greater than those found in cortex. In cerebellum, CsA was below the limit of detection. These data suggest that at clinically relevant doses, CsA may not affect CABP-D 28-kDa levels in brain.

Effect of vitamin D metabolites and analogs on renal and intestinal calbindin-D in the rat.

The effects on renal and intestinal calbindin-D of vitamin D3 metabolites and synthetic 20-epi-vitamin D3 analogs with different calcemic actions were examined in Wistar rats. The compounds were administered intraperitoneally once daily for 5 days. The dosages of the metabolites were 1,25-(OH)2D3 0.01, 0.05, 0.1, and 0.4 microg/kg x d, 24,25-(OH)2D3 0.1, 1 and 10 microg/kg x d, and 25-(OH)D3 10 and 400 microg/kg x d. The dosage of the synthetic analogs were MC903 0. 1, 10, and 100 microg/kg x d, EB1213 0.1 and 10 microg/kg x d, KH1060 0.1 and 0.4 microg/kg x d, and GS1725 0.01 and 0.1 microg/kg x d. Two control groups had either vehicle alone or no treatment. N = 8 in each group. 1,25-(OH)2D3 increased renal and intestinal calbindin-D levels, induced hypercalcemia, and suppressed plasma PTH and magnesium concentrations. 24,25-(OH)2D3 increased intestinal calbindin-D9k and plasma calcium, but had no effect on renal calbindin-D28k, plasma PTH, and magnesium. The dosage of 24, 25-(OH)2D3 that was required to increase plasma calcium was larger than the dosage required to increase intestinal calbindin-D9k. 25-(OH)D3 did not change the calcium metabolic parameters. MC903, a low calcemic analog with a relative high affinity for the vitamin D receptor and a short half-life, increased renal calbindin-D28k without increasing ionized calcium or intestinal calbindin-D9k. EB1213, an analog with a reduced calcemic action and short half-life, increased renal calbindin-D28k and ionized calcium without increasing intestinal calbindin-D9k. The effect of the high calcemic vitamin D analogs KH1060 and GS1725 on calbindin-D was directly related to their calcemic activity. In conclusion, these results demonstrate that 24,25-(OH)2D3 increases intestinal calbindin-D9k, but has no effect on renal calbindin-D28k, that low calcemic analogs may increase renal calbindin-D28k without increasing intestinal calbindin-D9k, and that the effect of high calcemic analogs on calbindin-D is directly related to their calcemic activity.

Urinary 28-kD calbindin-D as a new marker for damage to distal renal tubules caused by cisplatin-based chemotherapy.

Calbindin-D, a vitamin D-dependent calcium-binding protein of 28 kD, is found predominantly in the distal tubules of the kidney and central nervous system tissues in humans. To evaluate damage to the renal tubules caused by cisplatin-based chemotherapy, levels of urinary and serum calbindin-D were determined in patients treated with cisplatin- or carboplatin-based chemotherapies using a highly sensitive enzyme immunoassay system developed in our laboratory. Levels of urinary 28-kD calbindin-D were also determined in patients with benign and malignant urological diseases. The mean urinary calbindin-D level was 2.44 + or - 0.31 (mean + or - SE) ng/mg creatinine in 40 healthy subjects. Urinary calbindin-D levels were elevated (>10 ng/mg creatinine) in 2 of 33 patients (6%) with benign and 1 of 50 (2%) with malignant urological diseases. Urinary calbindin-D levels were significantly increased after cisplatin-based chemotherapy in 14 patients, with peaks (71.8 + or - 13.5 ng/mg creatinine) being found 8 days after administration of cisplatin, and then a gradual return to the baseline. On the other hand, 7 patients receiving carboplatin-based chemotherapy demonstrated no significant elevation (highest level 7.7 + or - 2.5 ng/mg creatinine). In 7 patients treated with cisplatin-based chemotherapy the serum calbindin-D level was also raised after treatment, with a good correlation to urinary values. These findings suggest that urinary and serum calbindin-D may be kidney-derived and that 28-kDa calbindin-D is a useful marker for damage to the distal renal tubules associated with cisplatin-based chemotherapy.

Increased Levels of Calbindin-D in Serum and Urine from Patients Treated by Extracorporeal Shock Wave Lithotripsy

Calbindin-D 28kDa. is a vitamin D-dependent calcium binding protein that is found mainly in the distal renal tubules and central nervous tissue in humans. Calbindin-D was measured in the serum and urine before, and immediately, 2hours or 24hours after extracorporeal shock wave lithotripsy (ESWL**Dornier Medical Systems, Inc., Marietta, Georgia.) in 83 consecutive patients. ESWL was performed with the Siemens Lithostar device in 61 patients and with the Dornier MPL9000 lithotriptor in 22. The serum 28kDa. calbindin-D level was undetectable (less than 20pg./ml.) in many samples, whereas urinary 28kDa. calbindin-D could be detected in every sample. The serum 28kDa. calbindin-D level was usually elevated after ESWL and the concentration in patients treated with the MPL9000 device was greater than in those treated with the Lithostar instrument. Urinary 28kDa. calbindin-D levels were elevated significantly immediately and at 2hours after ESWL, and they decreased to the baseline level within 24hours after ESWL in the Lithostar group but remained consistently significantly elevated after ESWL in the MPL9000 group. This fact may be because the MPL9000 lithotriptor produces a stronger shock wave than does the Lithostar device during ESWL. These results suggest that 28kDa. calbindin-D is released from damaged distal renal tubule cells into the serum and urine during ESWL and that 28kDa. calbindin-D is a specific marker for renal damage by ESWL. To our knowledge this is the first clinical study using a sensitive enzyme immunoassay for human 28kDa. calbindin-D to estimate renal damage during ESWL.

Developmental and Age‐Dependent Changes of 28‐kDa Calbindin‐D in the Central Nervous Tissue Determined with a Sensitive Immunoassay Method

For the quantitative analysis of vitamin D-dependent 28-kDa calcium-binding protein (calbindin-D) in the CNS, we have established a highly sensitive immunoassay method. The antisera were raised in rabbits with purified calbindin-D from rat kidneys, and the antibodies were purified with a calbindin-D-coupled Sepharose column. The purified antibodies were specific for calbindin-D, showing a single band on the immunoblot with the extract of rat kidney or cerebellum. The sandwich-type immunoassay system was prepared by the use of purified monospecific antibodies, and the minimum detection limit of the assay was 0.1 pg or 3.6 amol of calbindin-D, which was sufficiently sensitive for the measurement of calbindin-D content in isolated Purkinje cell bodies at the level of single cells. The average content of calbindin-D in a single Purkinje cell was 0.05 pg. Calbindin-D was detected in most of the rat tissues examined, but it was present predominantly in the kidney and CNS, especially in the cerebellum. Calbindin-D was detected at a similarly low level in the cerebral cortex, cerebellum, and brainstem of rat embryos of 15 gestational days, and it increased gradually but differently in these regions, reaching the respective adult levels by 4-5 weeks of postnatal age. In contrast, kidney calbindin-D increased sharply between 15 gestational days and 3 postnatal days, reaching the adult level by 6 days of age. Calbindin-D levels in the adult rat CNS were affected little by age, whereas the concentrations in human cerebral cortices were significantly low in the aged brain as compared with those in the young brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Intestinal calcium and lead absorption: Effects of dietary lead and calcium

The combined effects of dietary calcium (Ca) and lead (Pb) status on intestinal Ca and Pb absorption and related parameters were investigated in young growing chicks. Dietary Pb intake resulted in two remarkable, apparently independent and essentially opposite effects on intestinal Ca and Pb absorption, depending on dietary Ca and Pb levels and duration of treatment. The initial response (1 week) to Ca deficiency was stimulated Ca absorption and calbindin-D level, regardless of dietary Pb intake. The later response (2 weeks) was a reversal, by Pb, of the early phase stimulation. Intestinal Pb absorption was similarly enhanced by Ca deficiency initially, and this response was also inhibited by prolonged dietary Pb intake. Ingestion of Pb by chicks fed adequate Ca resulted in generally elevated intestinal Ca absorption and calbindin-D levels after both 1 and 2 weeks. Intestinal Pb absorption was also increased in the adequate Ca situation, but only after 2 weeks at the lower levels of dietary Pb. The results underscore the complicated nature of Pb-Ca interactions and demonstrate the importance of thorough characterization of the animal model system.