bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of prostate cancer growth by vitamin D: Regulation of target gene expression
Authors: Krishnan Aruna V. , Peehl Donna M. , Feldman David 
Published: January 2003

AbstractProstate cancer (PCa) cells express vitamin D receptors (VDR) and 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) inhibits the growth of epithelial cells derived from normal, benign prostate hyperplasia, and PCa as well as established PCa cell lines. The growth inhibitory effects of 1,25(OH)2D3 in cell cultures are modulated tissue by the presence and activities of the enzymes 25‐hydroxyvitamin D3 24‐hydroxylase which initiates the inactivation of 1,25(OH)2D3 and 25‐hydroxyvitamin D3 1α‐hydroxylase which catalyses its synthesis. In LNCaP human PCa cells 1,25(OH)2D3 exerts antiproliferative activity predominantly by cell cycle arrest through the induction of IGF binding protein‐3 (IGFBP‐3) expression which in turn increases the levels of the cell cycle inhibitor p21 leading to growth arrest. cDNA microarray analyses of primary prostatic epithelial and PCa cells reveal that 1,25(OH)2D3 regulates many target genes expanding the possible mechanisms of its anticancer activity and raising new potential therapeutic targets. Some of these target genes are involved in growth regulation, protection from oxidative stress, and cell–cell and cell–matrix interactions. A small clinical trial has shown that 1,25(OH)2D3 can slow the rate of prostate specific antigen (PSA) rise in PCa patients demonstrating proof of concept that 1,25(OH)2D3 exhibits therapeutic activity in men with PCa. Further investigation of the role of calcitriol and its analogs for the therapy or chemoprevention of PCa is currently being pursued. J. Cell. Biochem. 88: 363–371, 2003. © 2002 Wiley‐Liss, Inc.
Synthetic LXXLL peptide antagonize 1,25‐dihydroxyvitamin D3‐dependent transcription
Authors: Pike J. Wesley , Pathrose Peterman , Barmina Olga , Chang Ching‐Yi , McDonnell Donald P. , Yamamoto Hironori , Shevde Nirupama K. 
Published: January 2003

AbstractThe vitamin D receptor (VDR) is known to mediate the biological actions of 1,25‐dihydroxyvitamin D3 (1,25(OH)2D3) through its ability to regulate cellular programs of gene expression. We identified VDR‐ and retinoid X receptor (RXR)‐interacting LXXLL peptides using a mammalian two‐hybrid system and examined whether these molecules could block vitamin D and 9‐cis retinoic acid (9‐cis RA) response. Peptides were identified that were reactive to RXR alone as well as to both VDR and RXR. Peptide fusion proteins were then examined in MC3T3 E1 cells for their ability to block induction of the osteocalcin promoter by 1,25(OH)2D3 or stimulation of an RARE‐TK reporter by 9‐cis RA. Peptides that interacted with both VDR and RXR blocked 1,25(OH)2D3‐dependent transcription by up to 75%. Peptides that interacted with RXR blocked 9‐cis RA induced transcription. Two RXR‐interacting peptides, however, were also found to block 1,25(OH)2D3 response effectively. These studies support the idea that comodulator recruitment is essential for VDR‐ and RXR‐mediated gene expression and that RXR is required for 1,25(OH)2D3‐induced osteocalcin gene transcription. This approach may represent a novel means of assessing the contribution of RXR in various endogenous biological responses to 1,25(OH)2D3. J. Cell. Biochem. 88: 252–258, 2003. © 2002 Wiley‐Liss, Inc.
Molecular basis of the selective activity of vitamin D analogues
Authors: Carlberg Carsten 
Published: January 2003

AbstractMore than 2,000 synthetic analogues of the biological active form of vitamin D, 1α,25‐dihydroxyvitamin D3 (1α,25(OH)2D3), are presently known. Basically, all of them interfere with the molecular switch of nuclear 1α,25(OH)2D3 signaling, which is the complex of the vitamin D receptor (VDR), the retinoid X receptor (RXR), and a 1α,25(OH)2D3 response element (VDRE). Central element of this molecular switch is the ligand‐binding domain (LBD) of the VDR, which can be stabilized by a 1α,25(OH)2D3 analogue either in its agonistic, antagonistic, or non‐agonistic conformation. The positioning of helix 12 of the LBD is of most critical importance for these conformations. In each of the three conformations, the VDR performs different protein–protein interactions, which then result in a characteristic functional profile. Most 1α,25(OH)2D3 analogues have been identified as agonists, a few are antagonists (e.g., ZK159222 and TEI‐9647), and only Gemini and some of its derivatives act under restricted conditions as non‐agonists. The functional profile of some 1α,25(OH)2D3 analogues, such as EB1089 and Gemini, can be modulated by protein and DNA interaction partners of the VDR. This provides them with some selectivity for DNA‐dependent and ‐independent signaling pathways and VDRE structures. J. Cell. Biochem. 88: 274–281, 2003. © 2002 Wiley‐Liss, Inc.
Vitamin D: A millenium perspective
Authors: Holick Michael F. 
Published: January 2003

AbstractVitamin D is one of the oldest hormones that have been made in the earliest life forms for over 750 million years. Phytoplankton, zooplankton, and most plants and animals that are exposed to sunlight have the capacity to make vitamin D. Vitamin D is critically important for the development, growth, and maintenance of a healthy skeleton from birth until death. The major function of vitamin D is to maintain calcium homeostasis. It accomplishes this by increasing the efficiency of the intestine to absorb dietary calcium. When there is inadequate calcium in the diet to satisfy the body's calcium requirement, vitamin D communicates to the osteoblasts that signal osteoclast precursors to mature and dissolve the calcium stored in the bone. Vitamin D is metabolized in the liver and then in the kidney to 1,25‐dihydroxyvitamin D [1,25(OH)2D]. 1,25(OH)2D receptors (VDR) are present not only in the intestine and bone, but in a wide variety of other tissues, including the brain, heart, stomach, pancreas, activated T and B lymphocytes, skin, gonads, etc. 1,25(OH)2D is one of the most potent substances to inhibit proliferation of both normal and hyperproliferative cells and induce them to mature. It is also recognized that a wide variety of tissues, including colon, prostate, breast, and skin have the enzymatic machinery to produce 1,25(OH)2D. 1,25(OH)2D and its analogs have been developed for treating the hyperproliferative disease psoriasis. Vitamin D deficiency is a major unrecognized health problem. Not only does it cause rickets in children, osteomalacia and osteoporosis in adults, but may have long lasting effects. Chronic vitamin D deficiency may have serious adverse consequences, including increased risk of hypertension, multiple sclerosis, cancers of the colon, prostate, breast, and ovary, and type 1 diabetes. There needs to be a better appreciation of the importance of vitamin D for overall health and well being. J. Cell. Biochem. 88: 296–307, 2003. © 2002 Wiley‐Liss, Inc.
Vitamin D regulated keratinocyte differentiation: Role of coactivators
Authors: Bikle D.D. , Tu C.‐L. , Xie Z. , Oda Y. 
Published: January 2003

Abstract1,25 Dihydroxyvitamin D (1,25(OH)2D) regulates the differentiation of keratinocytes. 1,25(OH)2D raises intracellular free calcium (Cai) as a necessary early step toward stimulating differentiation. 1,25(OH)2D induces the calcium sensing receptor (CaR) in keratinocytes and enhances the calcium response of these cells. Activation of the CaR by calcium increases intracellular free calcium by a mechanism involving phospholipase C (PLC) cleavage of phosphatidylinositolbisphosphate into inositoltrisphosphate (IP3) and diacylglycerol (DG). 1,25(OH)2D induces the family of PLCs. PLC‐γ1 has a DR6 VDRE in its promoter which binds and is activated by VDR/RAR rather than VDR/RXR. The involucrin gene, which encodes a critical component of the cornified envelope, contains a DR3 VDRE in its promoter that acts in conjunction with a nearby AP‐1 site. The sequential regulation of these genes is critical for the differentiation process. In undifferentiated keratinocytes, the VDR binds preferentially to the DRIP complex of coactivators. However, with differentiation DRIP 205 is no longer produced, and the VDR switches partners to the SRC family (SRC2 and 3). These studies suggest that at least part of the sequential activation of genes required during keratinocyte differentiation is regulated by the change (availability) of these different coactivator complexes. J. Cell. Biochem. 88: 290–295, 2003. © 2002 Wiley‐Liss, Inc.
Prostatic 25‐hydroxyvitamin D‐1α‐hydroxylase and its implication in prostate cancer
Authors: Chen Tai C. , Wang Lilin , Whitlatch Lyman W. , Flanagan John N. , Holick Michael F. 
Published: January 2003

AbstractEvidence suggests that vitamin D may have a protective role for prostate cancer. 1α,25‐Dihydroxyvitamin D [1α,25(OH)2D] inhibits growth and induces differentiation of prostate cells. 25‐Hydroxyvitamin D‐1α‐hydroxylase [1α‐OHase], the enzyme that is responsible for the synthesis of 1α,25(OH)2D, is expressed in cultured prostate cells. We observed a marked decrease in 1α‐OHase activity in prostate cancer cells, suggesting some defect of the 1α‐OHase in these cells. To investigate whether the defect was due to dysregulation of the enzyme at the promoter level, a series of deletion constructs of the promoter was synthesized and incorporated upstream into the luciferase reporter gene. Two regions were identified with high basal activity in transfected normal prostate cell line (PZHPV‐7), −1100 bp (AN2), and −394 bp (AN5) upstream of ATG start site of the 1α‐OHase gene. When the reporter gene with either AN2 or AN5 was transfected into prostate cancer cell lines, we observed a lower basal promoter activity in PC‐3 cells and DU145 cells than that found in PZHPV‐7 cells for both constructs, and a loss of promoter activity in LNCaP cells. Thus, the results suggest that the defect in enzyme activity may result from the decreased promoter activity in prostate cancer cells. J. Cell. Biochem. 88: 315–322, 2003. © 2002 Wiley‐Liss, Inc.
Vitamin D regulation of the renin–angiotensin system
Authors: Li Yan Chun 
Published: January 2003

AbstractThe renin–angiotensin system (RAS) plays a central role in the regulation of blood pressure, electrolyte, and volume homeostasis. Epidemiological and clinical studies have long suggested an association of inadequate sunlight exposure or low serum 1,25‐dihydroxyvitamin D3 [1,25(OH)2D3] levels with high blood pressure and/or high plasma renin activity, but the mechanism is not understood. Our recent discovery that 1,25(OH)2D3 functions as a potent negative endocrine regulator of renin gene expression provides some insights into the mechanism. The concept of vitamin D regulation of blood pressure through the RAS opens a new avenue to our understanding of the physiological functions of the vitamin D endocrine system, and provides a basis for exploring the potential use of vitamin D analogues in prevention and treatment of hypertension. J. Cell. Biochem. 88: 327–331, 2003. © 2002 Wiley‐Liss, Inc.
Vitamin D and autoimmune diabetes
Authors: Zella Julia B. , DeLuca Hector F. 
Published: January 2003

AbstractThe biologically active form of vitamin D, 1,25(OH)2D3, is a potent modulator of the immune system as well as a regulator of bone and mineral metabolism. Vitamin D‐deficiency in infancy and vitamin D receptor gene polymorphisms may be risk factors for insulin‐dependent Diabetes mellitus (IDDM). 1,25(OH)2D3 and its analogs significantly repress the development of insulitis and diabetes in the non‐obese diabetic (NOD) mouse, a model of human IDDM. 1,25(OH)2D3 may modulate IDDM disease pathogenesis by repression of type I cytokines, inhibition of dendritic cell maturation, and upregulation of regulatory T cells. The function of vitamin D as a genetic and environmental determining factor for IDDM, the protective role of 1,25(OH)2D3 and its analogs in a mouse model of IDDM, and the possible mechanisms by which this protection occurs will be reviewed. J. Cell. Biochem. 88: 216–222, 2003. © 2002 Wiley‐Liss, Inc.
Rat cytochrome P450C24 (CYP24) does not metabolize 1,25‐dihydroxyvitamin D2 to calcitroic acid
Authors: Horst R.L. , Omdahl J.A. , Reddy S. 
Published: January 2003

Abstract1α‐Hydroxy‐23 carboxy‐24,25,26,27‐tetranorvitamin D3 (calcitroic acid) is known to be the major water‐soluble metabolite produced during the deactivation of 1,25‐(OH)2D3. This deactivation process is carried out exclusively by the multicatalytic enzyme CYP24 and involves a series of oxidation reactions at C24 and C23 leading to side‐chain cleavage and, ultimately, formation of the calcitroic acid. Like 1,25‐(OH)2D3, 1α,25‐1,25‐(OH)2D2 is also known to undergo side‐chain oxidation and side‐chain cleavage to form calcitroic acid (Zimmerman et al. [2001]. 1,25‐(OH)2D2 differs from 1,25‐(OH)2D3 by the presence of a double bond at C22 and a methyl group at C24. To date, there have been no studies detailing the participation of CYP24 in the production of calcitroic acid from 1,25‐(OH)2D2. We, therefore, studied the metabolism of 1,25‐(OH)2D3 and 1,25‐(OH)2D2 using a purified rat CYP24 system. Lipid and aqueous‐soluble metabolites were prepared for characterization. Aqueous‐soluble metabolites were subjected to reverse‐phase high‐pressure liquid chromatography (HPLC) analysis. As expected, 1,23(OH)2‐24,25,26,27‐tetranor D and calcitroic acid were the major lipid and aqueous‐soluble metabolites, respectively, when 1,25‐(OH)2D3 was used as substrate. However, when 1,25‐(OH)2D2 was used as substrate, 1,24(R),25‐(OH)3D2 was the major lipid‐soluble metabolite with no evidence for the production of either 1,23(OH)2‐24,25,26,27‐tetranor D or calcitroic acid. Apparently, the CYP24 was able to 24‐hydroxylate 1,25‐(OH)2D2, but was unable to effect further changes, which would result in side‐chain cleavage. These data suggest that the presence of either the double bond at C22 or the C24 methyl group impedes the metabolism of 1,25‐(OH)2D2 to calcitroic acid by CYP24 and that enzymes other than CYP24 are required to effect this process. J. Cell. Biochem. 88: 282–285, 2003. Published 2002 Wiley‐Liss, Inc.
Intranuclear trafficking of transcription factors: Requirements for vitamin D‐mediated biological control of gene expression
Authors: Stein Gary S. , Lian Jane B. , Stein Janet L. , van Wijnen André J. , Montecino Martin , Javed Amjad , Pratap Jitesh , Choi Je , Zaidi S. Kaleem , Gutierrez Soraya , Harrington Kimberly , Shen Jiali , Young Daniel 
Published: January 2003

AbstractThe architecturally associated subnuclear organization of nucleic acids and cognate regulatory factors suggest functional interrelationships between nuclear structure and gene expression. Mechanisms that contribute to the spatial distribution of transcription factors within the three‐dimensional context of nuclear architecture control the sorting of regulatory information as well as the assembly and activities of sites within the nucleus that support gene expression. Vitamin D control of gene expression serves as a paradigm for experimentally addressing mechanisms that govern the intranuclear targeting of regulatory factors to nuclear domains where transcription of developmental and tissue‐specific genes occur. We will present an overview of molecular, cellular, genetic, and biochemical approaches that provide insight into the trafficking of regulatory factors that mediate vitamin D control of gene expression to transcriptionally active subnuclear sites. Examples will be presented that suggest modifications in the intranuclear targeting of transcription factors abrogate competency for vitamin D control of skeletal gene expression during development and fidelity of gene expression in tumor cells. J. Cell. Biochem. 88: 340–355, 2003. © 2002 Wiley‐Liss, Inc.
Inhibitors of vitamin D hydroxylases: Structure–activity relationships
Authors: Schuster Inge , Egger Helmut , Nussbaumer Peter , Kroemer Romano T. 
Published: January 2003

AbstractAiming at new drugs to efficiently treat diseases, in which either increased or decreased levels of active vitamin D are desirable, we have designed some 400 structurally different azole‐type inhibitors and examined their capacity to selectively block vitamin D metabolism by CYP24 or synthesis by CYP27B, in human keratinocytes. Based on resulting data, we built pharmacophore models of the active sites using commercial software. The overlay of potent selective compounds indicated similar docking modes in the two‐substrate pockets and allowed for identification of bioactive conformations. Superimposing these bioactive conformations with low energy conformers of 25(OH)D3 suggested that the substrate‐mimicked by strong inhibitors in size, shape and lipophilic character‐binds to both enzymes in 6s‐trans configuration. Pharmacophoric models implied a similar geometry of the substrate sites, nevertheless specific features of CYP24 and CYP27B could be defined. Bulky substituents in α‐position to the azole caused selectivity for CYP24, whereas bulky substituents in β‐position could result in selectivity for CYP27B. Moreover, studies with small sterically restricted inhibitors revealed a probable location of the 3‐OH‐group of 25(OH)D3 in CYP27B. In the absence of crystal structures, our inhibitors are valuable tools to model and understand the active sites of vitamin D hydroxylases, resulting in the design of powerful, selective therapeutics. J. Cell. Biochem. 88: 372–380, 2003. © 2002 Wiley‐Liss, Inc.
Positional information by rauber's sickle and a new look at the mechanisms of primitive streak initiation in avian blastoderms
Authors: Callebaut Marc , Van Nueten Emmy , Bortier Hilde , Harrisson Fernand 
Published: January 2003

AbstractThe present experimental in vitro study suggests that a primitive streak (PS) in avian blastoderms is induced by diffusion of morphogenetic substances emanating from Rauber's sickle. Indeed, even without direct contact between a quail Rauber's sickle and the reacting upper layer (by interposition of a vitelline membrane), a PS can be induced in the isolated area centralis or antisickle region of unincubated chicken blastoderms. The so‐formed PSs are localized below the vitelline membrane in the immediate neighborhood of the apposed Rauber's sickle material. This seems to indicate that Rauber's sickle organizes the formation of the avian PS according to the basic concept of “positional information.” The morphogenetic substances seem to have an effect only on the formation of a PS. Each part of Rauber's sickle seems to have, point by point, the same thickening and PS‐inducing effect on each corresponding part of the underlying upper layer (UL). By a mechanism of sliding over the basement membrane and fusion, this finally results in the formation of one single median PS. Our study shows that a PS can be induced in the total absence of hypoblast (sickle endoblast) or caudal marginal zone, by only the presence of Rauber's sickle material. In contrast, the differentiation of mesoblast into blood islands under the influence of Rauber's sickle and neural tissue development are impaired by the interposition of a vitelline membrane. The latter could be due to the absence of a normal interaction of Rauber's sickle‐derived sickle endoblast with endophyll and/or upper layer and the absence of cranial migration of the mesoblast. Thus, earlier studies and the present study indicate the existence of a temporospatially bound cascade of gastrulation and neurulation phenomena and blood island formation in the avian blastoderm, starting from Rauber's sickle, the primary major organizer with inducing, inhibiting, and dominating potencies. The latter not only plays a role by secretion of signaling molecules, but also influences development by its cell lineages (junctional endoblast and sickle endoblast). J. Morphol. 255:315–327, 2003. © 2003 Wiley‐Liss, Inc.
Microscopic anatomy of the orbital harderian gland in the common tree shrew (tupaia glis)
Authors: Pradidarcheep Wisuit , Asavapongpatana Somluk , Mingsakul Thaworn , Poonkhum Raksawan , Nilbu‐nga Somneuk , Somana Reon 
Published: January 2003

AbstractThe orbital Harderian gland of the common tree shrew (Tupaia glis) was investigated at the macroscopic and microscopic levels. In the glands of both sexes only one acinar cell type was found. The cell is characterized by the presence of numerous lipid vacuoles of variable size and by a small number of PAS‐positive, electron‐dense granules distributed throughout the cytoplasm, which are predominant at the basal portion of each acinar cell. The duct system is well developed within the gland. The content of lipid vacuoles within the acinar cells is secreted from the apical portions by exocytosis, indicating the exocrine function of the organ. Apart from the lipid vacuoles, both acinar and ductal luminal contents of the Harderian gland also contain accretion of electron‐dense materials. The vascularization within the Harderian gland is unique in that two capillary types (small fenestrated and irregular sinusoidal capillaries) could be demonstrated. The presence of fenestrated capillaries together with other morphological features (such as accumulation of the small electron‐dense granules at the basal pole and the presence of basolateral microvilli) near the basal portion of the acinar cells suggest that the Harderian gland in T. glis might also be involved in an endocrine function. J. Morphol. 255:328–336, 2003. © 2003 Wiley‐Liss, Inc.
Immunocytochemical and ultrastructural characterization of mammosomatotrope‐, growth hormone‐, and prolactin‐cells from the gilthead sea bream (sparus aurata l., teleostei): an ontogenic study
Authors: Villaplana Mariano , García Ayala Alfonsa , Hernández Maria Pilar García , Agulleiro Blanca 
Published: January 2003

AbstractGrowth hormone (GH), prolactin (PRL), and mammosomatotrope (MS) cells of gilthead sea bream, Sparus aurata, a teleost fish, were studied in specimens from hatching to 15 months (adults) using conventional electron microscopy and an immunogold method using anti‐tilapia GH sera and anti‐chum salmon PRL serum. MS cells, immunoreactive to both anti‐GH sera and anti‐PRL sera, had been first identified in fish in a previous study in newly hatched larvae and in older larvae and juvenile specimens of Sparus aurata by light microscopic immunocytochemistry. In the present work, MS cells reacted positively to immunogold label only in older larvae and juveniles and their secretory granules immunoreacted with both GH and PRL antisera or with only one of them. MS cells were ultrastructurally similar to the PRL cells, with which they coincided in time. This is the first report on the ultrastructural characterization of MS cells in fish. In adults, the secretory granules of GH cells (immunoreactive to anti‐GH serum) were mainly round, of variable size, and had a homogeneous, highly electron‐dense content. Irregularly shaped secretory granules were also present. PRL cells (immunoreactive to anti‐PRL serum) were usually observed in a follicular arrangement; they showed few, small, and mainly round secretory granules with a homogeneous and high or medium electron‐dense content. Some oval or elongated secretory granules were also observed. GH and PRL cells that showed involutive features were also found. In newly hatched larvae, GH, PRL, and MS cells could not be distinguished either by their ultrastructure or by the immunogold labeling of the secretory granules. In 1‐day‐old larvae, presumptive GH and PRL cells were observed according to their position in the pituitary gland. In 2‐day‐old larvae, a few cells showed some of the ultrastructural features described for GH and PRL cells of adults. During development, the number, size, and shape of the secretory granules in both cell types clearly increased and the organelles developed gradually. Some GH cells were found undergoing mitosis. J. Morphol. 255:347–357, 2003. © 2003 Wiley‐Liss, Inc.