Dexamethasone Modulates Nonvisual Opsins, Glucocorticoid Receptor, and Clock Genes inDanio rerioZEM-2S Cells

Here we report, for the first time, the differential cellular distribution of two melanopsins (Opn4m1 and Opn4m2) and the effects of GR agonist, dexamethasone, on the expression of these opsins and clock genes, in the photosensitiveD. rerioZEM-2S embryonic cells. Immunopositive labeling for Opn4m1 was detected in the cell membrane whereas Opn4m2 labeling shows nuclear localization, which did not change in response to light.opn4m1,opn4m2,gr,per1b,andcry1bpresented an oscillatory profile of expression in LD condition. In both DD and LD condition, dexamethasone (DEX) treatment shifted the peak expression ofper1bandcry1btranscripts to ZT16, which corresponds to the highestopn4m1expression. Interestingly, DEX promoted an increase ofper1bexpression when applied in LD condition but a decrease when the cells were kept under DD condition. Although DEX effects are divergent with different light conditions, the response resulted in clock synchronization in all cases. Taken together, these data demonstrate thatD. rerioZEM-2S cells possess a photosensitive system due to melanopsin expression which results in an oscillatory profile of clock genes in response to LD cycle. Moreover, we provide evidence that glucocorticoid acts as a circadian regulator ofD. rerioperipheral clocks.

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Intracellular Localization of the Glucocorticoid Receptor: Evidence for Cytoplasmic and Nuclear Localization*

Endocrinology ◽

10.1210/endo-120-4-1232 ◽

1987 ◽

Vol 120 (4) ◽

pp. 1232-1242 ◽

Cited By ~ 131

Author(s):

ANN-CHARLOTTE WIKSTRÖM ◽

ODDMUND BAKKE ◽

SAM OKRET ◽

MIKAEL BRÖNNEGÅRD ◽

JAN-ÅKE GUSTAFSSON

Keyword(s):

Glucocorticoid Receptor ◽

Nuclear Localization ◽

Intracellular Localization

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Entrainment of peripheral clock genes by cortisol

Physiological Genomics ◽

10.1152/physiolgenomics.00001.2012 ◽

2012 ◽

Vol 44 (11) ◽

pp. 607-621 ◽

Cited By ~ 34

Author(s):

Panteleimon D. Mavroudis ◽

Jeremy D. Scheff ◽

Steve E. Calvano ◽

Stephen F. Lowry ◽

Ioannis P. Androulakis

Keyword(s):

Clock Genes ◽

Dynamic Regime ◽

The Body ◽

Molecular Function ◽

Frequency Range ◽

Peripheral Tissues ◽

Peripheral Clock ◽

Peripheral Clocks ◽

Central Pacemaker ◽

Peripheral Cells

Circadian rhythmicity in mammals is primarily driven by the suprachiasmatic nucleus (SCN), often called the central pacemaker, which converts the photic information of light and dark cycles into neuronal and hormonal signals in the periphery of the body. Cells of peripheral tissues respond to these centrally mediated cues by adjusting their molecular function to optimize organism performance. Numerous systemic cues orchestrate peripheral rhythmicity, such as feeding, body temperature, the autonomic nervous system, and hormones. We propose a semimechanistic model for the entrainment of peripheral clock genes by cortisol as a representative entrainer of peripheral cells. This model demonstrates the importance of entrainer's characteristics in terms of the synchronization and entrainment of peripheral clock genes, and predicts the loss of intercellular synchrony when cortisol moves out of its homeostatic amplitude and frequency range, as has been observed clinically in chronic stress and cancer. The model also predicts a dynamic regime of entrainment, when cortisol has a slightly decreased amplitude rhythm, where individual clock genes remain relatively synchronized among themselves but are phase shifted in relation to the entrainer. The model illustrates how the loss of communication between the SCN and peripheral tissues could result in desynchronization of peripheral clocks.

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Sites of insulin and glucagon metabolism in the rabbit nephron

AJP Renal Physiology ◽

10.1152/ajprenal.1986.250.1.f144 ◽

1986 ◽

Vol 250 (1) ◽

pp. F144-F150 ◽

Cited By ~ 1

Author(s):

R. Nakamura ◽

M. Hayashi ◽

D. S. Emmanouel ◽

A. I. Katz

Keyword(s):

Cell Membrane ◽

Insulin Degradation ◽

Distal Nephron ◽

Hormone Metabolism ◽

Nephron Segments ◽

Straight Tubules ◽

Collecting Tubules ◽

First Time ◽

Convoluted Tubules ◽

Substantial Degree

Uptake and degradation of peptide hormones have been demonstrated in proximal convoluted tubules (PCT), but the contribution of other regions of the nephron to renal hormone metabolism is unknown. In the present study we used micromethods to determine for the first time the degradation of radiolabeled insulin and glucagon by each segment of the rabbit nephron and examined some characteristics of this process in proximal convoluted and cortical collecting tubules (CCT). Degradation of insulin (8-10 fmol . cm-1 . h-1) and glucagon (13-15 fmol . cm-1 . h-1) was maximal in proximal convoluted and straight tubules, but occurred to a substantial degree (approximately 25-30% of PCT) in all other segments of the nephron except the thin descending limb. In PCT degradation of both hormones was maximal at physiological pH, and competition studies suggested that it is brought about by both specific and nonspecific proteases. Most of the degrading activity (insulin, 86%; glucagon, 73%) was in the cytosol or could be eluted off the cell membrane or organelles. In the CCT, a representative segment of the distal nephron, the characteristics of insulin degradation were similar to those observed in the PCT, whereas glucagon degradation appeared to be due chiefly to nonspecific proteases. In conclusion, the metabolism of insulin and glucagon by isolated rabbit tubules occurs chiefly in the proximal convoluted and straight tubules, but up to one-third of the degrading capacity of the proximal nephron is also present in distal nephron segments.(ABSTRACT TRUNCATED AT 250 WORDS)

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Glucocorticoid receptor in the rat epididymis: Expression, cellular distribution and regulation by steroid hormones

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2010.05.013 ◽

2010 ◽

Vol 325 (1-2) ◽

pp. 64-77 ◽

Cited By ~ 25

Author(s):

Erick J.R. Silva ◽

Daniel B.C. Queiróz ◽

Luciana Honda ◽

Maria Christina W. Avellar

Keyword(s):

Glucocorticoid Receptor ◽

Steroid Hormones ◽

Cellular Distribution ◽

Rat Epididymis

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Pendulin, a Drosophila protein with cell cycle-dependent nuclear localization, is required for normal cell proliferation.

The Journal of Cell Biology ◽

10.1083/jcb.129.6.1491 ◽

1995 ◽

Vol 129 (6) ◽

pp. 1491-1507 ◽

Cited By ~ 79

Author(s):

P Küssel ◽

M Frasch

Keyword(s):

Cell Cycle ◽

Cell Proliferation ◽

Nuclear Localization ◽

Growth Regulation ◽

Tandem Repeats ◽

Sequence Similarity ◽

Intracellular Localization ◽

Abnormal Development ◽

Embryonic Cells ◽

Cycle Dependent

We describe the dynamic intracellular localization of Drosophila Pendulin and its role in the control of cell proliferation. Pendulin is a new member of a superfamily of proteins which contains Armadillo (Arm) repeats and displays extensive sequence similarities with the Srp1 protein from yeast, with RAG-1 interacting proteins from humans, and with the importin protein from Xenopus. Almost the entire polypeptide chain of Pendulin is composed of degenerate tandem repeats of approximately 42 amino acids each. A short NH2-terminal domain contains adjacent consensus sequences for nuclear localization and cdc2 kinase phosphorylation. The subcellular distribution of Pendulin is dependent on the phase of cell cycle. During interphase, Pendulin protein is exclusively found in the cytoplasm of embryonic cells. At the transition between G2 and M-phase, Pendulin rapidly translocates into the nuclei where it is distributed throughout the nucleoplasm and the areas around the chromosomes. In the larval CNS, Pendulin is predominantly expressed in the dividing neuroblasts, where it undergoes the same cell cycle-dependent redistribution as in embryos. Pendulin is encoded by the oho31 locus and is expressed both maternally and zygotically. We describe the phenotypes of recessive lethal mutations in the oho31 gene that result in a massive decrease or loss of zygotic Pendulin expression. Hematopoietic cells of mutant larvae overproliferate and form melanotic tumors, suggesting that Pendulin normally acts as a blood cell tumor suppressor. In contrast, growth and proliferation in imaginal tissues are reduced and irregular, resulting in abnormal development of imaginal discs and the CNS of the larvae. This phenotype shows that Pendulin is required for normal growth regulation. Based on the structure of the protein, we propose that Pendulin may serve as an adaptor molecule to form complexes with other proteins. The sequence similarity with importin indicates that Pendulin may play a role in the nuclear import of karyophilic proteins and some of these may be required for the normal transmission and function of proliferative signals in the cells.

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Nuclear and nuclear envelope binding proteins of the glucocorticoid receptor nuclear localization peptide identified by crosslinking

The Journal of Steroid Biochemistry and Molecular Biology ◽

10.1016/0960-0760(91)90193-9 ◽

1991 ◽

Vol 40 (1-3) ◽

pp. 279-285 ◽

Cited By ~ 5

Author(s):

Eric C. LaCasse ◽

Yvonne A. Lefebvre

Keyword(s):

Glucocorticoid Receptor ◽

Nuclear Envelope ◽

Nuclear Localization ◽

Binding Proteins

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Relevance of drug uptake, cellular distribution and cell membrane fluidity to the enhanced sensitivity of Down's syndrome fibroblasts to anticancer antibiotic—mitoxantrone

Biochimica et Biophysica Acta (BBA) - Biomembranes ◽

10.1016/s0005-2736(03)00051-8 ◽

2003 ◽

Vol 1611 (1-2) ◽

pp. 161-170 ◽

Cited By ~ 6

Author(s):

Maria Przybylska ◽

Zofia Jóźwiak

Keyword(s):

Cell Membrane ◽

Membrane Fluidity ◽

Down's Syndrome ◽

Down’S Syndrome ◽

Drug Uptake ◽

Cellular Distribution ◽

Enhanced Sensitivity ◽

Cell Membrane Fluidity

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PKCε Phosphorylates and Mediates the Cell Membrane Localization of RhoA

ISRN Oncology ◽

10.1155/2013/329063 ◽

2013 ◽

Vol 2013 ◽

pp. 1-9

Author(s):

Tizhi Su ◽

Samuel Straight ◽

Liwei Bao ◽

Xiujie Xie ◽

Caryn L. Lehner ◽

...

Keyword(s):

Protein Kinase C ◽

Cell Membrane ◽

Cell Invasion ◽

Time Course ◽

Time Lapse ◽

Kinase C ◽

Phosphorylation Event ◽

Phosphopeptide Mapping ◽

First Time ◽

Initial Peak

Protein kinase Cε (PKCε) signals through RhoA to modulate cell invasion and motility. In this study, the multifaceted interaction between PKCε and RhoA was defined. Phosphopeptide mapping revealed that PKCε phosphorylates RhoA at T127 and S188. Recombinant PKCε bound to recombinant RhoA in the absence of ATP indicating that the association between PKCε and RhoA does not require an active ATP-docked PKCε conformation. Activation of PKCε resulted in a dramatic coordinated translocation of PKCε and RhoA from the cytoplasm to the cell membrane using time-lapse fluorescence microscopy. Stoichiometric FRET analysis revealed that the molecular interaction between PKCε and RhoA is a biphasic event, an initial peak at the cytoplasm and a gradual prolonged increase at the cell membrane for the entire time-course (12.5 minutes). These results suggest that the PKCε-RhoA complex is assembled in the cytoplasm and subsequently recruited to the cell membrane. Kinase inactive (K437R) PKCε is able to recruit RhoA to the cell membrane indicating that the association between PKCε and RhoA is proximal to the active catalytic site and perhaps independent of a PKCε-RhoA phosphorylation event. This work demonstrates, for the first time, that PKCε phosphorylates and modulates the cell membrane translocation of RhoA.

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