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Pharmacology & Toxicology 2000Calbindin-D28k is an intracellular protein with high affinity for calcium. In the kidney, this protein is exclusively localized in the distal tubule and in the proximal... (Review)
Review
Calbindin-D28k is an intracellular protein with high affinity for calcium. In the kidney, this protein is exclusively localized in the distal tubule and in the proximal part of the collecting ducts. Functionally, calbindin-D28k is supposed to be involved in the regulation of the reabsorption of calcium and possibly magnesium in the distal nephron though the exact regulatory mechanisms are not yet known. Thus, several theories regarding the functional role of calbindin-D28k have been proposed: The carrier theory describes calbindin-D28k as a transport protein which binds calcium and then transports it from the luminal to the basolateralcell membrane. The buffer theory assumes that calbindin-D28k functions by binding calcium ions to prevent intracellular calcium concentrations from reaching toxic levels. The activator theory describes that calbindin-D28k increases the activity of calcium channels or the enzymatic activity of the Ca++-Mg++-ATPase in the luminal membrane and thereby increases the tubular reabsorption of calcium. The renal calbindin-D28k is dependent upon vitamin D. Pharmacological doses of the active vitamin D metabolite 1,25-(OH)2D increases the concentrations of renal calbindin-D28k, whereas the concentration of calbindin-D28k is low in conditions with reduced levels of circulating 1,25-(OH)2D. Likewise, plasma calcium concentrations, uremia and hypertension affect calbindin-D28k expression. However, several studies have rendered probable the effect of additional factors in the regulation of renal calbindin-D28k. The aim of the present dissertation therefore was to examine the regulation of renal calbindin-D28k in a series of physiological and pathophysiological conditions established in vivo in the rat. A possible correlation between hypertension and calbindin-D28k was examined in three models of experimental hypertension: the genetically defined spontaneous hypertensive rat, the salt-sensitive Dahl rat and the renovascular hypertensive rat. These three models clearly demonstrated three separate patterns in the calcium metabolism, but the studies were unable to support a role for calbindin-D28k in the development of hypertension. In all three models the development of hypertension caused an increased plasma 1,25-(OH)2D. This increase was accompanied by either unaltered or reduced levels of renal calbindin-D28k possibly secondary to a cellular resistance against 1,25-(OH)2D. Magnesium binds to calbindin-D28k with a relatively high affinity. The regulation of urinary magnesium excretion takes place in the distal tubule where calbindin-D28k is found in high concentrations. Therefore, a possible relation between magnesium and calbindin-D28k was examined. The studies demonstrated not previously known connections between magnesium intake, urinary magnesium excretion and renal calbindin-D28k which suggests that this protein is involved in the regulation of magnesium homeostasis by the kidney. Calcitonin increases the reabsorption of calcium in the distal tubule. Therefore, the effect ofcalcitonin on renal calbindin-D28k was examined both by eliminating the endogeneous calcitonin production by a selective thyroidectomy followed by an autotransplantation of the parathyroid glands and further by infusion of calcitonin. These studies demonstrated unchanged concentrations of renal calbindin-D28k. It was concluded that the increased calcium reabsorption induced by calcitonin in the distal tubule is not mediated by calbindin-D28k. Urinary calcium excretion is in part regulated by the action of PTH on calcium reabsorption in the distal nephron. Previous reports of increased expression of renal calbindin-D28k in uremic rats led us to suggest that secondary hyperparathyroidism associated with uremia induced the synthesis of renal calbindin-D28k. Therefore, the effect of PTH was examined in a study comprising selective parathyroidectomy and infusions of PTH, PTHrP, 1,25-(OH)2D and calcium. (ABSTRACT TRUNCATED)
Topics: Animals; Calbindin 1; Calbindins; Calcium; Hypertension, Renal; Kidney; S100 Calcium Binding Protein G; Vitamin D
PubMed: 11097107
DOI: No ID Found -
Clinical Orthopaedics and Related... Apr 1991This review summarizes current knowledge on the distribution of the vitamin-D-dependent, calcium-binding protein, calbindin-D9k, an indicator of 1,25(OH)2D3 action, in... (Review)
Review
This review summarizes current knowledge on the distribution of the vitamin-D-dependent, calcium-binding protein, calbindin-D9k, an indicator of 1,25(OH)2D3 action, in mineralized tissues, with emphasis on the cellular and subcellular distribution of the protein. Light and electron microscopic immunolocalization studies have shown that calbindin-D9k is present in cartilage and bone. In cartilage, it is restricted to the mature chondrocytes. In bone, it is present in osteoblasts and osteocytes. In both, its synthesis is vitamin D dependent. While calbindin-D9k is a strictly cytosolic protein in soft tissues, it has a specific distribution in mineralized tissues and may even be extracellular. Hence, it is restricted to the lateral edges of the longitudinal septa in the epiphyseal cartilage, the same area in which matrix vesicles are found. Calbindin-D9k lies within the matrix vesicles and is also found in the matrix vesicles near the mineralizing front of trabecular and compact bone. It seems to remain in position over the crystallites formed from the matrix vesicles in fully calcified cartilage and in heavily mineralized bone. The protein is also present in teeth, in the ameloblasts of incisors and molars but not in odontoblasts. The data suggest that calbindin-D9k is required for mineral nucleation in the matrix vesicles of epiphyseal cartilage and bone. The synthesis and distribution of calbindin-D9k in normal and rachitic normal bone and cartilage indicate that vitamin D has a direct action on mineralizing tissues.
Topics: Animals; Bone and Bones; Calbindins; Cartilage; Rats; S100 Calcium Binding Protein G; Tooth; Vitamin D
PubMed: 2009668
DOI: No ID Found -
International Journal of Molecular... Nov 2013Calbindin-D9k (CaBP-9k) binds calcium with high affinity and regulates the distribution of free calcium in the cytoplasm. The expression of CaBP-9k is detected primarily... (Review)
Review
Calbindin-D9k (CaBP-9k) binds calcium with high affinity and regulates the distribution of free calcium in the cytoplasm. The expression of CaBP-9k is detected primarily in intestine that is vitamin D target tissue, and accumulates in the enterocytes of the duodenal villi. These enterocytes are the clearest example of vitamin D responsive cells, and the presence of CaBP-9k within them accentuates calcium absorption mediated by active transcellular calcium transport. It has been well established that the expression of CaBP-9k is mediated with vitamin D response element on its promoter and it regulates the amount of intracellular calcium in order to prevent cell death from reaching the toxicity of free calcium. There is now little doubt that glucocorticoid also decreases CaBP-9k expression in duodenal epithelial cells. In addition, it was reported that the level of CaBP-9k gene in enterocytes is increased in pregnancy when the plasma estradiol concentration is generally associated with a concomitant increase. Although calcium homeostasis was not disturbed in mice lacking the CaBP-9k gene, we found that CaBP-9k has a buffering role of free calcium in the cytosolic environment beyond that of calcium transfer. To expand our knowledge of the biological functions of CaBP-9k, our research has focused on defining the biological significance of intracellular CaBP-9k. Our findings suggest that the CaBP-9k gene is involved in compensatory induction of other calcium transporter genes in duodenal epithelial cells. This article summarizes the findings from recent studies on the expression and the functions of CaBP-9k in the small intestine.
Topics: Animals; Calbindins; Calcium; Calcium Channels; Duodenum; Enterocytes; Humans; Receptors, Calcitriol; Vitamin D
PubMed: 24287909
DOI: 10.3390/ijms141223330 -
Neuroscience Dec 1997Calbindin-D28k is a member of the large EF-hand family of calcium-binding proteins, that is believed to function, in part as a cytosolic calcium buffer. Recent studies...
Calbindin-D28k is a member of the large EF-hand family of calcium-binding proteins, that is believed to function, in part as a cytosolic calcium buffer. Recent studies have demonstrated that cells containing Calbindin-D28k are protected from degeneration caused by conditions that elevate intracellular calcium concentrations. Since its initial discovery in 1966, Calbindin-D28k has been localized in the cytoplasm of many neuronal populations, but its nuclear localization has been uncertain. Using light and electron microscopic immunohistochemistry, and nuclear fractionation methods, we demonstrate localization of Calbindin-D28k not only in the cytoplasm, but also in the nucleus of rodent midbrain dopaminergic neurons and cerebellar Purkinje cells. The Calbindin-D28k immunoreactive staining intensity in the nucleus was routinely equal or greater than that in the cytoplasm. Since calcium signals are propagated to the nucleus, where they can regulate gene expression, the existence of nuclear Calbindin-D28k has important implications for cellular function.
Topics: Animals; Calbindin 1; Calbindins; Cell Nucleus; Immunohistochemistry; Male; Mice; Mice, Inbred C57BL; Microscopy, Electron; Neurons; S100 Calcium Binding Protein G; Subcellular Fractions
PubMed: 9316025
DOI: 10.1016/s0306-4522(97)00206-6 -
Danish Medical Bulletin Jun 1991
Review
Topics: Animals; Calbindins; Humans; Intestine, Small; Kidney; S100 Calcium Binding Protein G
PubMed: 1868755
DOI: No ID Found -
Hippocampus Jul 2021The midline thalamus bidirectionally connects the medial prefrontal cortex (mPFC) and hippocampus (HC) creating a unique cortico-thalamo-cortical circuit fundamental to...
The midline thalamus bidirectionally connects the medial prefrontal cortex (mPFC) and hippocampus (HC) creating a unique cortico-thalamo-cortical circuit fundamental to memory and executive function. While the anatomical connectivity of midline thalamus has been thoroughly investigated, little is known about its cellular organization within each nucleus. Here we used immunohistological techniques to examine cellular distributions in the midline thalamus based on the calcium binding proteins parvalbumin (PV), calretinin (CR), and calbindin (CB). We also examined these calcium binding proteins in a population of reuniens cells known to project to both mPFC and HC using a dual fluorescence retrograde adenoassociated virus-based tracing approach. These dual reuniens mPFC-HC projecting cells, in particular, are thought to be important for synchronizing mPFC and HC activity. First, we confirmed the absence of PV neurons in the midline thalamus. Second, we found a common pattern of CR and CB cells throughout midline thalamus with CR cells running along the nearby third ventricle (3V) and penetrating the midline. CB cells were consistently more lateral and toward the middle of the dorsal-ventral extent of the midline thalamus. Notably, single-labeled CR and CB zones were partially overlapping and included dual-labeled CR /CB cells. Within RE, we also observed a CR and CB subzone specific diversity. Interestingly, dual mPFC-HC projecting neurons in RE expressed none of the calcium binding proteins examined, but were contained in nests of CR and CB cells. Overall, the midline thalamus was well organized into CR and CB rich zones distributed throughout the region, with dual mPFC-HC projecting cells in reuniens representing a unique cell population. These results provide a cytoarchitectural organization in the midline thalamus based on calcium binding protein expression, and set the stage for future cell-type specific interrogations of the functional role of these different cell populations in mPFC-HC interactions.
Topics: Calbindin 2; Calbindins; Hippocampus; Midline Thalamic Nuclei; Prefrontal Cortex; Thalamus
PubMed: 33085824
DOI: 10.1002/hipo.23271 -
Advances in Experimental Medicine and... 1990
Review
Topics: Animals; Calbindins; Calcium; Cattle; Cell Line; Isomerism; Protein Engineering; S100 Calcium Binding Protein G; Structure-Activity Relationship
PubMed: 2191561
DOI: 10.1007/978-1-4684-5754-4_6 -
Journal of Chemical Neuroanatomy Dec 2003The entorhinal cortex is an essential component in the organization of the human hippocampal formation related to cortical activity. It transfers, neocortical... (Review)
Review
The entorhinal cortex is an essential component in the organization of the human hippocampal formation related to cortical activity. It transfers, neocortical information (ultimately distributed to the dentate gyrus and hippocampus) and receives most of the hippocampal output directed to neocortex. At birth, the human entorhinal cortex presents similar layer organization as in adults, although layer II (cell islands) and upper layer III have a protracted maturation. The presence of interneurons expressing calcium-binding proteins (parvalbumin, calbindin-D28K (calbindin) and calretinin) is well documented in the adult human entorhinal cortex. In many of them the calcium binding is co-localized with GABA. Parvalbumin-immunoreactive cells and fibers were virtually absent at birth, their presence increasing gradually in deep layer III, mostly in the lateral and caudal portions of the entorhinal cortex from the 5th month onwards. Calbindin immunoreactive cells and fibers were present at birth, mainly in layers II and upper III; mostly at rostral and lateral portions of the entorhinal cortex, increasing in number and extending to deep layers from the 5th month onwards. Calretinin immunoreactivity was present at birth, homogeneously distributed over layers I, II and upper V, throughout the entorhinal cortex. A substantial increase in the number of calretinin neurons in layer V was observed at the 5th month. The postnatal development of parvalbumin, calbindin and calretinin may have an important role in the functional maturation of the entorhinal cortex through the control of hippocampal, cortical and subcortical information.
Topics: Calbindin 1; Calbindin 2; Calbindins; Child, Preschool; Entorhinal Cortex; Female; Humans; Immunohistochemistry; Infant; Interneurons; Parvalbumins; Pregnancy; S100 Calcium Binding Protein G
PubMed: 14729133
DOI: 10.1016/j.jchemneu.2003.09.005 -
Current Opinion in Nephrology and... Jul 2000The identification of a putative apical Ca++ channel in 1,25dihydroxyvitamin D3 responsive epithelia (proximal intestine and the distal nephron) as well as recent... (Review)
Review
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.
Topics: Animals; Calbindin 1; Calbindins; Calcitriol; Calcium; Humans; Kidney; Mice; Mice, Knockout; S100 Calcium Binding Protein G; Urothelium
PubMed: 10926169
DOI: 10.1097/00041552-200007000-00004 -
Anatomical Record (Hoboken, N.J. : 2007) May 2021The hypothalamus is involved in the regulation of rhythms, autonomic, endocrine, and behavioral functions and may also participate in aging development and control. The...
The hypothalamus is involved in the regulation of rhythms, autonomic, endocrine, and behavioral functions and may also participate in aging development and control. The aim of this work was to study the expression of calbindin (CB) and calretinin (CR) in the ventromedial (VMH) and dorsomedial (DMH) hypothalamic nuclei in young and old rats of both sexes by immunohistochemistry and western blotting. In young animals, the largest number of CB-immunoreactive (IR) neurons was detected in the ventral part of DMH (DMHv) and smaller percentage was found in its dorsal part (DMHd), in the dorsomedial part of the VMH (VMHdm) and in the ventrolateral part of the VMH (VMHvl). In aged animals, the percentage of CB-IR neurons significantly decreased in all studied nuclei, including DMHv, DMHd, VMHdm and VMHvl. CR-IR neurons were found in moderate number in the DMHv, DMHd, VMHdm and VMHvl of young rats. In aged rats, the percentage of CR-IR neurons significantly increased in the DMHv, DMHd, VMHdm and VMHvl. Less than one third of IR neurons colocalized CB and CR in young and aged rats. The expression of CB significantly decreased, and the expression of CR significantly increased in the DMH and VMH during aging by western blot analysis. Thus, there are opposite changes of the calcium-binding proteins expression in the hypothalamic nuclei involved in the metabolic and sexual regulation during aging.
Topics: Aging; Animals; Calbindin 2; Calbindins; Dorsomedial Hypothalamic Nucleus; Female; Male; Neurons; Rats; Ventromedial Hypothalamic Nucleus
PubMed: 33040447
DOI: 10.1002/ar.24536