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Cold Spring Harbor Perspectives in... Nov 2010"Ca(2+) buffers," a class of cytosolic Ca(2+)-binding proteins, act as modulators of short-lived intracellular Ca(2+) signals; they affect both the temporal and spatial... (Review)
Review
"Ca(2+) buffers," a class of cytosolic Ca(2+)-binding proteins, act as modulators of short-lived intracellular Ca(2+) signals; they affect both the temporal and spatial aspects of these transient increases in [Ca(2+)](i). Examples of Ca(2+) buffers include parvalbumins (α and β isoforms), calbindin-D9k, calbindin-D28k, and calretinin. Besides their proven Ca(2+) buffer function, some might additionally have Ca(2+) sensor functions. Ca(2+) buffers have to be viewed as one of the components implicated in the precise regulation of Ca(2+) signaling and Ca(2+) homeostasis. Each cell is equipped with proteins, including Ca(2+) channels, transporters, and pumps that, together with the Ca(2+) buffers, shape the intracellular Ca(2+) signals. All of these molecules are not only functionally coupled, but their expression is likely to be regulated in a Ca(2+)-dependent manner to maintain normal Ca(2+) signaling, even in the absence or malfunctioning of one of the components.
Topics: Animals; Buffers; Calbindin 1; Calbindin 2; Calbindins; Calcium; Calcium Signaling; Cations, Divalent; Cytosol; Homeostasis; Humans; Parvalbumins; S100 Calcium Binding Protein G
PubMed: 20943758
DOI: 10.1101/cshperspect.a004051 -
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 -
The Journal of Clinical Investigation Jul 2023Increased levels and diversity of human endogenous retrovirus (HERV) transcription characterize most cancer types and are linked with disease outcomes. However, the...
Increased levels and diversity of human endogenous retrovirus (HERV) transcription characterize most cancer types and are linked with disease outcomes. However, the underlying processes are incompletely understood. Here, we show that elevated transcription of HERVH proviruses predicted survival of lung squamous cell carcinoma (LUSC) and identified an isoform of CALB1, encoding calbindin, ectopically driven by an upstream HERVH provirus under the control of KLF5, as the mediator of this effect. HERVH-CALB1 expression was initiated in preinvasive lesions and associated with their progression. Calbindin loss in LUSC cell lines impaired in vitro and in vivo growth and triggered senescence, consistent with a protumor effect. However, calbindin also directly controlled the senescence-associated secretory phenotype (SASP), marked by secretion of CXCL8 and other neutrophil chemoattractants. In established carcinomas, CALB1-negative cancer cells became the dominant source of CXCL8, correlating with neutrophil infiltration and worse prognosis. Thus, HERVH-CALB1 expression in LUSC may display antagonistic pleiotropy, whereby the benefits of escaping senescence early during cancer initiation and clonal competition were offset by the prevention of SASP and protumor inflammation at later stages.
Topics: Humans; Calbindins; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cellular Senescence; Endogenous Retroviruses; Lung Neoplasms; Proviruses
PubMed: 37192000
DOI: 10.1172/JCI164397 -
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 -
Journal of Biochemical and Molecular... Jul 2022Since 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...
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/kg ip). 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.
Topics: Acute Kidney Injury; Animals; Antineoplastic Agents; Biomarkers; Calbindins; Cisplatin; Kidney; Male; Mice; Mice, Inbred C57BL
PubMed: 35403300
DOI: 10.1002/jbt.23068 -
The Journal of Histochemistry and... Aug 2022Herein, we aimed to use double-labeling immunofluorescence to describe the expression pattern of Calbindin-D28K (CaBP28K) in the mouse cochlea from late embryonic (E)...
Herein, we aimed to use double-labeling immunofluorescence to describe the expression pattern of Calbindin-D28K (CaBP28K) in the mouse cochlea from late embryonic (E) stages to the adulthood. CaBP28K was expressed in the inner hair cells (IHCs) and the greater epithelial ridge (GER) at E17. In addition, its expression was observed in the interdental cells. On postnatal day 1 (P1), CaBP28K immunoreactivity was observed in the IHCs and outer hair cells (OHCs) and was also specifically expressed in the nucleus and the cytoplasm of spiral ganglion neurons (SGNs). At P8, CaBP28K labeling disappeared from the interdental cells, and the CaBP28K-positive domain within the GER shifted from the entire cytoplasm to only the apical and basal regions. At P14, CaBP28K immunoreactivity was lost from the GER; however, its expression in the IHCs and OHCs, as well as the SGNs, persisted into adulthood. The identification of CaBP28K in the hair cells (HCs) and cuticular plates, as well as SGNs, was confirmed by its colocalization with several markers for Sox2, Myosin VIIa, Phalloidin, and Tuj1. We also detected colocalization with calmodulin in the cytoplasm of both HCs and SGNs. Western blot revealed an increase in CaBP28K postnatal expression in the mouse cochlea.
Topics: Animals; Calbindin 1; Cochlea; Fluorescent Antibody Technique; Immunohistochemistry; Mice; Neurons; Spiral Ganglion
PubMed: 35975307
DOI: 10.1369/00221554221119543 -
Anatomical Record (Hoboken, N.J. : 2007) May 2020The claustrum (CLA) is a subcortical structure that is reciprocally and topographically connected with the cerebral cortex. The complexity of the cerebral cortex varies...
The claustrum (CLA) is a subcortical structure that is reciprocally and topographically connected with the cerebral cortex. The complexity of the cerebral cortex varies dramatically across mammals, raising the question of whether there might also be differences in CLA organization, circuitry, and function. Species variations in the shape of the CLA are well documented. Studies in multiple species have identified subsets of neurochemically distinct interneurons; some data suggest species variations in the nature, distribution, and numbers of different neurochemically identified neuronal types. We have studied the CLA in a smooth-brained primate, the squirrel monkey, using Nissl-stained sections and immunohistochemistry. We found that the shape of the CLA is different from that in other primates. We found several different neurochemically defined populations of neurons equally distributed throughout the CLA. Immunoreactivity to GAD and GABA receptors suggest that GABAergic interneurons provide widespread inhibitory input to CLA neurons. Immunoreactivity to glutamate transporters suggests widespread and overlapping excitatory input from cortical and possibly subcortical sources. Comparison of CLA organization in different species suggests that there may be major species differences both in the organization and in the functions of the CLA. Anat Rec, 303:1439-1454, 2020. © 2019 American Association for Anatomy.
Topics: Amino Acid Transport System X-AG; Animals; Calbindins; Claustrum; GABAergic Neurons; Immunohistochemistry; Interneurons; Neurons; Saimiri
PubMed: 31509339
DOI: 10.1002/ar.24253 -
Aging Cell Aug 2017As it was established that aging is not associated with massive neuronal loss, as was believed in the mid-20th Century, scientific interest has addressed the influence... (Review)
Review
As it was established that aging is not associated with massive neuronal loss, as was believed in the mid-20th Century, scientific interest has addressed the influence of aging on particular neuronal subpopulations and their synaptic contacts, which constitute the substrate for neural plasticity. Inhibitory neurons represent the most complex and diverse group of neurons, showing distinct molecular and physiological characteristics and possessing a compelling ability to control the physiology of neural circuits. This review focuses on the aging of GABAergic neurons and synapses. Understanding how aging affects synapses of particular neuronal subpopulations may help explain the heterogeneity of aging-related effects. We reviewed the literature concerning the effects of aging on the numbers of GABAergic neurons and synapses as well as aging-related alterations in their presynaptic and postsynaptic components. Finally, we discussed the influence of those changes on the plasticity of the GABAergic system, highlighting our results concerning aging in mouse somatosensory cortex and linking them to plasticity impairments and brain disorders. We posit that aging-induced impairments of the GABAergic system lead to an inhibitory/excitatory imbalance, thereby decreasing neuron's ability to respond with plastic changes to environmental and cellular challenges, leaving the brain more vulnerable to cognitive decline and damage by synaptopathic diseases.
Topics: Aging; Animals; Calbindin 2; Calbindins; Cell Count; Cognitive Dysfunction; GABAergic Neurons; Gene Expression Regulation; Glutamate Decarboxylase; Humans; Mice; Neuronal Plasticity; Receptors, GABA; Somatosensory Cortex; Somatostatin; Synapses; gamma-Aminobutyric Acid
PubMed: 28497576
DOI: 10.1111/acel.12605 -
The Journal of Comparative Neurology Dec 2023Accurate anatomical characterizations are necessary to investigate neural circuitry on a fine scale, but for the rodent claustrum complex (CLCX), this has yet to be...
Accurate anatomical characterizations are necessary to investigate neural circuitry on a fine scale, but for the rodent claustrum complex (CLCX), this has yet to be fully accomplished. The CLCX is generally considered to comprise two major subdivisions, the claustrum (CL) and the dorsal endopiriform nucleus (DEn), but regional boundaries to these areas are debated. To address this, we conducted a multifaceted analysis of fiber- and cytoarchitecture, genetic marker expression, and connectivity using mice of both sexes, to create a comprehensive guide for identifying and delineating borders to CLCX, including an online reference atlas. Our data indicated four distinct subregions within CLCX, subdividing both CL and DEn into two. Additionally, we conducted brain-wide tracing of inputs to CLCX using a transgenic mouse line. Immunohistochemical staining against myelin basic protein (MBP), parvalbumin (PV), and calbindin (CB) revealed intricate fiber-architectural patterns enabling precise delineations of CLCX and its subregions. Myelinated fibers were abundant dorsally in CL but absent ventrally, whereas PV expressing fibers occupied the entire CL. CB staining revealed a central gap within CL, also visible anterior to the striatum. The Nr2f2, Npsr1, and Cplx3 genes expressed specifically within different subregions of the CLCX, and Rprm helped delineate the CL-insular border. Furthermore, cells in CL projecting to the retrosplenial cortex were located within the myelin sparse area. By combining own experimental data with digitally available datasets of gene expression and input connectivity, we could demonstrate that the proposed delineation scheme allows anchoring of datasets from different origins to a common reference framework.
Topics: Male; Female; Mice; Animals; Claustrum; Calbindins; Brain; Parvalbumins; Rodentia; Nerve Tissue Proteins; Adaptor Proteins, Signal Transducing
PubMed: 37782702
DOI: 10.1002/cne.25539 -
International Journal of Molecular... Feb 2022Amyloid β (Aβ(1-42)) oligomers have been linked to the pathogenesis of Alzheimer's disease (AD). Intracellular calcium (Ca) homeostasis dysregulation with subsequent...
Amyloid β (Aβ(1-42)) oligomers have been linked to the pathogenesis of Alzheimer's disease (AD). Intracellular calcium (Ca) homeostasis dysregulation with subsequent alterations of neuronal excitability has been proposed to mediate Aβ neurotoxicity in AD. The Ca binding proteins calmodulin (CaM) and calbindin-D28k, whose expression levels are lowered in human AD brains, have relevant roles in neuronal survival and activity. In previous works, we have shown that CaM has a high affinity for Aβ(1-42) oligomers and extensively binds internalized Aβ(1-42) in neurons. In this work, we have designed a hydrophobic peptide of 10 amino acid residues: VFAFAMAFML (amidated-C-terminus amino acid) mimicking the interacting domain of CaM with Aβ (1-42), using a combined strategy based on the experimental results obtained for Aβ(1-42) binding to CaM and in silico docking analysis. The increase in the fluorescence intensity of Aβ(1-42) HiLyte-Fluor555 has been used to monitor the kinetics of complex formation with CaM and with calbindin-D28k. The complexation between nanomolar concentrations of Aβ(1-42) and calbindin-D28k is also a novel finding reported in this work. We found that the synthetic peptide VFAFAMAFML (amidated-C-terminus amino acid) is a potent inhibitor of the formation of Aβ(1-42):CaM and of Aβ(1-42):calbindin-D28k complexes.
Topics: Alzheimer Disease; Amino Acids; Amyloid beta-Peptides; Calbindins; Calcium; Calmodulin; Humans; Neurons
PubMed: 35216403
DOI: 10.3390/ijms23042289