Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “ARF”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
PubMed1994

ArF excimer laser-induced bubble formation during irradiation of NaCl solutions.

During application of the 193 nm excimer laser to vitreoretinal surgery, very deep cutting of the retina of about 100 microm/pulse was detected at the energy fluence in the range of 0.25-0.35 J/cm2/pulse. At the surface of the ablating tip insoluble bubbles were observed during the irradiation. In this paper we study production of these bubbles in aqueous solutions of sodium chloride. The yield of gaseous photoproducts was measured as a function of NaCl concentration and energy fluence. At concentrations of 100 g/L powerful water vapor bubbles and shock waves were observed. A mechanism of soft tissue cutting by the 193 nm laser in highly absorbing liquid media is suggested that explains the features of vitreoretinal ablation with this system: (1) the high cutting depth when the tip touches the tissue and (2) the absence of cutting when the tip is not in contact with tissue. The advantages of the ArF laser for microsurgery of internal organs are discussed.

Lasers↗
PubMedDate not supplied

Assessment of expressions of heat shock protein (HSP 72) and apoptosis after ArF excimer laser ablation of the cornea.

We immunohistochemically studied expressions of inducible heat shock protein 70 (HSP 72) and apoptosis of corneas ablated with an ArF excimer laser. The temperature of corneal surfaces and laser-induced optical emission spectra were measured in real time as direct physical parameters related to the ablation mechanism. To the best of the authors' knowledge, there have been no experimental studies regarding the influence of physical parameters directly related to the ablation mechanism on corneal reactions at the cell level after laser ablation. The expression of HSP 72 was mainly localized in the regenerative epithelium, which was confirmed to be caused by laser ablation. The HSP 72 positive cell ratios had a correlation with thermal dose, which was derived from the measured time courses of temperature. Expressions of both HSP 72 and apoptosis depended on the thermal dose and elapsed time after ablation. HSP 72 and apoptosis could be seen up to a few hundred micrometers into the stroma, only at a fluence with an optical breakdown emission. This could have been caused by shock waves induced by the optical breakdown.

Animals↗
PubMed1999

Coordinated polar localization of auxin efflux carrier PIN1 by GNOM ARF GEF.

The plant hormone auxin is transported in a polar manner along the shoot-root axis, which requires efflux carriers such as PIN1. Asymmetric localization of PIN1 develops from a random distribution in Arabidopsis early embryogenesis. Coordinated polar localization of PIN1 is defective in gnom embryos. GNOM is a membrane-associated guanine-nucleotide exchange factor on ADP-ribosylation factor G protein (ARF GEF). Thus, GNOM-dependent vesicle trafficking may establish cell polarity, resulting in polar auxin transport.

ADP-Ribosylation Factors↗
PubMed1999

The E7 oncoprotein of human papillomavirus type 16 stabilizes p53 through a mechanism independent of p19(ARF).

High-risk human papillomaviruses are causally associated with cervical cancer. Two viral oncogenes, E6 and E7, are expressed in most cervical cancers, and these genes cause cancer when expressed in experimental animals. The E6 protein targets the p53 tumor suppressor for degradation, while the E7 protein inactivates the retinoblastoma susceptibility protein (pRb), in part by stimulating its degradation. In contrast, expression of E7 in the absence of E6 leads to stabilization of p53. Here we show that E7 stabilizes p53 in mouse embryo fibroblasts lacking p19(ARF). The stable p53 is active as a transcriptional activator, as evidenced by the increased expression of the p53-responsive mdm2 gene. Normally, MDM2 protein inhibits p53 function in an autoregulatory loop. Regulation of p53 by MDM2 is required for murine development as well as for proliferation of cultured human fibroblasts. However, E7-expressing human fibroblasts continue to divide even though E7 abrogates the ability of MDM2 and p53 to bind. Furthermore, E7-expressing cells are not more sensitive to UV light, an agent that has been reported to induce apoptosis mediated by p53. These results indicate that in addition to inhibiting the ability of MDM2 to regulate p53, E7 must block signaling steps downstream of p53 to allow cell division.

Animals↗
PubMed2001

Role of p14(ARF) in replicative and induced senescence of human fibroblasts.

Following a proliferative phase of variable duration, most normal somatic cells enter a growth arrest state known as replicative senescence. In addition to telomere shortening, a variety of environmental insults and signaling imbalances can elicit phenotypes closely resembling senescence. We used p53(-/-) and p21(-/-) human fibroblast cell strains constructed by gene targeting to investigate the involvement of the Arf-Mdm2-p53-p21 pathway in natural as well as premature senescence states. We propose that in cell types that upregulate p21 during replicative exhaustion, such as normal human fibroblasts, p53, p21, and Rb act sequentially and constitute the major pathway for establishing growth arrest and that the telomere-initiated signal enters this pathway at the level of p53. Our results also revealed a number of significant differences between human and rodent fibroblasts in the regulation of senescence pathways.

Aging↗
PubMed1999

"Orientation teeth" in non-mechanical laser corneal trephination for penetrating keratoplasty: 2.94 microm Er:YAG v 193 nm ArF excimer laser.

BACKGROUND/AIMS: "Orientation teeth" at the donor trephination margin and correspondent "notches" at the host margin facilitate graft orientation and avoid "horizontal torsion" induced by asymmetric suture placement. In this study the quality and reproducibility of these structures created by non-mechanical laser corneal trephination were compared using two laser emissions. METHODS: The procedure was performed in 20 enucleated pigs' eyes using open metal masks with eight "orientation teeth/notches" (0.3 x 0.15 mm, base x height), an automated globe rotation device, and either a 193 nm ArF excimer laser or a Q switched 2.94 microm Er:YAG laser. "Teeth/notches" were analysed by planimetry and scanning electron microscopy (SEM). RESULTS: Mean size was 0.30 (0.027) x 0. 16 (0.017) mm for "teeth" and 0.30 (0.035) x 0.15 (0.021) mm for "notches" (excimer), and 0.31 (0.022) x 0.16 (0.015) mm and 0.30 (0.031) x 0.14 (0.021) mm respectively (Er:YAG). Overall, variability of notches was higher than that of teeth. By SEM, comparable cut regularity and sustained ablation profile were observed with both lasers. However, the corneal surface at the cut edge appeared slightly elevated (</=35 microm) in the Er:YAG group. CONCLUSION: Orientation teeth/notches resembling those obtained with the excimer laser can be created using the Q switched Er:YAG laser, with potential advantages of lower costs, convenient equipment size, and solid state safety.

Animals↗
PubMed1996

Uninephrectomy reduces apoptotic cell death and enhances renal tubular cell regeneration in ischemic ARF in rats.

Contralateral uninephrectomy attenuates unilateral ischemic renal injury functionally and morphologically. In this study we investigated the effects of uninephrectomy on apoptotic renal cell death and tubular regeneration in ischemic acute renal failure (ARF) in rats. Unilateral ischemic injury was provoked by a 60-min left renal artery occlusion in right-nephrectomized (Nx) and sham-nephrectomized (sham-Nx) rats. Uninephrectomy attenuated tubular damage 48 h following the renal ischemia Apoptotic cells were found in renal tissue as early as 3 h after reperfusion and increased in number by 12 h. The "ladder" pattern of DNA fragments on agarose gel electrophoresis was also apparent in ischemic kidney. Uninephrectomy reduced apoptotic cells and DNA fragmentation. The expression of proliferating cell nuclear antigen (PCNA) could be seen 24 h after reperfusion and progressively increased thereafter PCNA expression in ischemic kidney was greater in Nx than sham-Nx rats at 24 h after renal reperfusion. These data suggest that uninephrectomy reduces apoptotic cells and DNA fragmentation and enhances PCNA expression. The reduced apoptotic cell death and enhanced cell regeneration may be importantly involved in the uninephrectomy-induced attenuation of ischemic acute renal failure in rats.

Acute Kidney Injury↗
PubMed2004

p16 and ARF: activation of teenage proteins in old age.

Cellular senescence induced by different stresses and telomere shortening appears to play an important role in the aging process. The products of the INK4a/ARF locus--p16INK4a and ARF--arrest cell proliferation at the senescence stage by exerting their effects on retinoblastoma protein- and p53-mediated responsive pathways. A study in this issue of the JCI provides experimental evidence of a specific upregulation of these cell cycle inhibitors in a variety of organs during mammalian aging.

ADP-Ribosylation Factor 1↗
PubMed2002

ATM mutations are associated with inactivation of the ARF-TP53 tumor suppressor pathway in diffuse large B-cell lymphoma.

The ATM serine-threonine kinase plays a central role in the cellular response to DNA damage. Germ-line mutations in the ATM gene cause ataxia-telangiectasia (A-T), a multisystem disorder associated with predisposition to lymphoma and acute leukemia. Moreover, somatic ATM mutations have been identified in T-cell prolymphocytic leukemia, mantle cell lymphoma, and B-cell chronic lymphocytic leukemia. In this study, the entire ATM coding sequence was examined in genomic DNA from 120 lymphoid neoplasms. Novel mutations and mutations implicated in cancer and/or A-T were found in 9 of 45 diffuse large B-cell lymphomas (DLBCLs), 2 of 24 follicular lymphomas, and 1 of 27 adult acute lymphoblastic leukemias, whereas no such mutations were detected among 24 peripheral T-cell lymphomas. The mutational spectrum consisted of 2 nonsense mutations, 1 mutation affecting RNA splicing, and 10 missense variants. Most of these mutations were associated with loss or mutation of the paired ATM allele, consistent with biallelic inactivation of ATM. Of the 9 DLBCLs with ATM mutations, 7 also carried TP53 mutations and/or deletions of the INK4a/ARF locus (P =.003). The ATM 735C>T substitution previously considered a rare normal variant was found to be 5.6 times more frequent in individuals with DLBCL than in random individuals (P =.026), suggesting that it may predispose to B-cell lymphoma. Our data suggest that ATM mutations contribute to the development of DLBCL, and that ATM and the ARF-p53 tumor suppressor pathway may cooperate in the pathogenesis of this malignancy.

Adult↗
PubMed2005

The domain architecture of large guanine nucleotide exchange factors for the small GTP-binding protein Arf.

BACKGROUND: Small G proteins, which are essential regulators of multiple cellular functions, are activated by guanine nucleotide exchange factors (GEFs) that stimulate the exchange of the tightly bound GDP nucleotide by GTP. The catalytic domain responsible for nucleotide exchange is in general associated with non-catalytic domains that define the spatio-temporal conditions of activation. In the case of small G proteins of the Arf subfamily, which are major regulators of membrane trafficking, GEFs form a heterogeneous family whose only common characteristic is the well-characterized Sec7 catalytic domain. In contrast, the function of non-catalytic domains and how they regulate/cooperate with the catalytic domain is essentially unknown. RESULTS: Based on Sec7-containing sequences from fully-annotated eukaryotic genomes, including our annotation of these sequences from Paramecium, we have investigated the domain architecture of large ArfGEFs of the BIG and GBF subfamilies, which are involved in Golgi traffic. Multiple sequence alignments combined with the analysis of predicted secondary structures, non-structured regions and splicing patterns, identifies five novel non-catalytic structural domains which are common to both subfamilies, revealing that they share a conserved modular organization. We also report a novel ArfGEF subfamily with a domain organization so far unique to alveolates, which we name TBS (TBC-Sec7). CONCLUSION: Our analysis unifies the BIG and GBF subfamilies into a higher order subfamily, which, together with their being the only subfamilies common to all eukaryotes, suggests that they descend from a common ancestor from which species-specific ArfGEFs have subsequently evolved. Our identification of a conserved modular architecture provides a background for future functional investigation of non-catalytic domains.

ADP-Ribosylation Factors↗
PubMed2005

Golgi-localized, gamma-ear-containing, Arf-binding protein adaptors mediate insulin-responsive trafficking of glucose transporter 4 in 3T3-L1 adipocytes.

Small glucose transporter 4 (Glut4)-containing vesicles represent the major insulin-responsive compartment in fat and skeletal muscle cells. The molecular mechanism of their biogenesis is not yet elucidated. Here, we studied the role of the newly discovered family of monomeric adaptor proteins, GGA (Golgi-localized, gamma-ear-containing, Arf-binding proteins), in the formation of small Glut4 vesicles and acquisition of insulin responsiveness in 3T3-L1 adipocytes. In these cells, all three GGA isoforms are expressed throughout the differentiation process. In particular, GGA2 is primarily present in trans-Golgi network and endosomes where it demonstrates a significant colocalization with the recycling pool of Glut4. Using the techniques of immunoadsorption as well as glutathione-S-transferase pull-down assay we found that Glut4 vesicles (but not Glut4 per se) interact with GGA via the Vps-27, Hrs, and STAM (VHS) domain. Moreover, a dominant negative GGA mutant inhibits formation of Glut4 vesicles in vitro. To study a possible role of GGA in Glut4 traffic in the living cell, we stably expressed a dominant negative GGA mutant in 3T3-L1 adipocytes. Formation of small insulin-responsive Glut4-containing vesicles and insulin-stimulated glucose uptake in these cells were markedly impaired. Thus, GGA adaptors participate in the formation of the insulin-responsive vesicular compartment from the intracellular donor membranes both in vivo and in vitro.

3T3-L1 Cells↗
PubMed2000

N-terminal targeting of guanine nucleotide exchange factors (GEF) for ADP ribosylation factors (ARF) to the Golgi.

B2-1 (cytohesin-1) is a member of a group of proteins (including ARNO and ARNO3) that are all of similar size and domain composition. The three proteins contain an N-terminal coiled-coil domain, followed by a Sec7 and a pleckstrin homology (PH) domain. While it is well established that the Sec7 domain functions as a guanine nucleotide exchange factor (GEF) for ADP-ribosylation factors (ARFs) and the PH domain anchors the proteins to membrane phosphoinositols, the function of the N-terminal domain is unknown. Here we show that the N terminus of B2-1 (residues 1-54) is necessary and sufficient to target the protein to the Golgi. The Sec7+PH domains of B2-1 (residues 55-398) are not sufficient for Golgi localization. Further deletion analysis and point mutagenesis indicate that the coiled-coil domain within the N terminus is responsible for Golgi targeting. Furthermore, ARNO and ARNO3 N termini also have the same capability of targeting to the Golgi. We conclude that the N-terminal, (&agr;)-helical, coiled-coil domain is used to target this family of proteins to the Golgi complex.

ADP-Ribosylation Factors↗
PubMed2004

Correlation between oxygen-deficient center formation and volume compaction in synthetic SiO2 glass upon ArF or F2 excimer-laser irradiation.

Correlations between the refractive-index change and the concentration of an oxygen-deficient center (ODC) induced by thermal treatments and laser irradiation are examined to clarify the origin of laser-induced volume compaction in synthetic SiO2 glasses. A linear correlation between them was clearly observed for thermally induced ODC, whereas no correlation was found for ArF or F2 laser irradiation. The results demonstrate that the dominant origin of laser-induced compaction is not ODC formation. Furthermore, we found that the presence of H2 in SiO2 glass had no influence on volume compaction but enhanced crack formation upon laser irradiation, a phenomenon most likely due to stress corrosion.

Journal Article↗
PubMed2003

Abundant expression of spliced HDM2 in Hodgkin lymphoma cells does not interfere with p14(ARF) and p53 binding.

Recently, comparative genomic hybridization (CGH)- and fluorescence in situ hybridization (FISH)-analyses of native Hodgkin and Reed-Sternberg (H&RS) cells extracted from Hodgkin lymphoma (HL) revealed a recurrent amplification of the HDM2 locus on chromosome 12. HDM2 is known to target, inactivate and to degrade p53. Wild type (wt) p53 protein is detected in high levels in HL. Simultaneously, stabilized wt p53 and spliced hdm2 transcripts have been observed in different tumors. Therefore, we examined the expression and structure of HDM2 in HL cell lines and possible effects on components of the p53 pathway. DNA integrity and induction potential of p53 was verified by DNA sequencing and detection of potential effector proteins (p21(WAF/CIP), HDM2) using immunofluorescence, respectively. All HL cell lines show an overexpression of HDM2 protein. Furthermore, several different spliced hdm2 transcripts (mdm-sv) including five new variants lacking a functional p53 binding site were characterized. If expressed, corresponding proteins were shown to be not restricted to the nucleus. Co-localization of the potential binding partners HDM2/p14(ARF) and HDM2/p53 was found in HL cell lines. We suggest that HDM2-sv have no significant disturbing influence on the interaction of these proteins.

Alternative Splicing↗
PubMed1998

A scanning and rotating slit arF excimer laser delivery system for refractive surgery.

PURPOSE: This study was designed to investigate the quality of a scanning and rotating slit delivery system of an ArF excimer laser (Nidek EC-5000). METHODS: The ablation patterns on polymethylmethacrylate (PMMA) wafers were examined by scanning electron microscopy. The influence of inhomogeneities in the beam profile was simulated on a computer and compared with a conventional large-area ablation system. The impairment of the ablation rate by radiation absorption of the ablation plume was measured as a function of the repetition rate and the application of a fixation ring. RESULTS: The scanning and rotating slit delivery system is tolerant of small-beam non-homogeneities. The ablation rate is sensitive to the dynamics of the ablation plume. CONCLUSIONS: Although the operating procedure takes less time with a large-area ablation system, a scanning and rotating delivery system has the advantage of reliable and homogeneous removal of corneal tissue.

Cornea↗
PubMed1999

Human corneal ablation threshold using the 193-nm ArF excimer laser.

PURPOSE: To determine the human corneal threshold ablation energy density for the 193-nm ArF excimer laser, approximating clinical conditions. METHODS: The VISX Star (Santa Clara, CA) 193-nm argon fluoride excimer laser was used to ablate the cornea in human eye bank eyes under clinical conditions. Corneas were exposed to energy densities of 10, 20, 30, 35, 40, 45, and 140 to 160 mJ/cm2. Corneas were fixed for light and transmission electron microscopy immediately after laser exposure. RESULTS: Different ablation thresholds for various corneal structural elements were observed. The ablation threshold for the collagen in the corneal stroma was determined to be 30 mJ/cm2. Keratocytes had ablation thresholds of 40 mJ/cm2. These different ablation thresholds accounted for the production of stromal peaks and valleys, with the keratocytes atop the peaks. CONCLUSIONS: Different corneal structural elements have different ablation threshold energy densities.

Collagen↗
PubMed2000

[The ARF-p53 pathway: a line of defence against oncogenic signals].

The MTS1 (Multiple Tumor Suppressor 1) locus is a very original one as its organization results in the expression of two alternative transcripts that encode two structurally and functionally different proteins: INK4a and ARF (also designated p19ARF in mouse and p14ARF in man). Recent findings indicate that the latter is a major component of a regulatory pathway of oncogenic signals culminating in p53 activation by stabilisation of the protein. While the importance of this pathway has been overtly established in animal experimental oncology, it still has to be further documented in human oncology in order for this gene to acquire its full biological significance.

Animals↗
PubMed2001

Comparative genomics of prokaryotic GTP-binding proteins (the Era, Obg, EngA, ThdF (TrmE), YchF and YihA families) and their relationship to eukaryotic GTP-binding proteins (the DRG, ARF, RAB, RAN, RAS and RHO families).

Several GTP-binding proteins with poorly defined functions were previously identified in Escherichia coli (i.e. Era, ThdF (TrmE)), Bacillus subtilis (i.e. Obg) and Neisseria gonorrhoeae (i.e. EngA). In these species, every individual protein is encoded by an essential gene. BLAST searches were used to detect orthologs in genomes of various organisms. Alignments of orthologous sequences allowed the construction of phylogenetic trees and the definition of protein families. The BLAST searches also resulted in the identification of two additional families, the YchF and YihA families, named after the ychF and yihA genes of E. coli. Most families are not present in archaeal genomes, but representatives of each family were also detected in eukaryotic genomes. Only representatives of the YchF family are present in every genome sequenced to date, suggesting that YchF-like proteins might be involved in a fundamental life process. The GTP1/DRG family consisting of eukaryotic and archaeal proteins is related to the YchF family of GTP-binding proteins. The relationship of the six prokaryotic families of GTP-binding proteins and the GTP1/DRG family to eukaryotic GTPase families was also investigated: With the exception of the ARF family, a clear separation of the six prokaryotic families and the GTP1/DRG family with respect to eukaryotic (RAB, RAN, RAS and RHO) GTPases was observed.

Animals↗