bluuebunny/crossref_metadata_2025_split huggingface dataset:
Angiotensin II induces peroxisome proliferator‐activated receptor gamma in PC12W cells via angiotensin type 2 receptor activation
Authors: Zhao Yi , Foryst‐Ludwig Anna , Bruemmer Dennis , Culman Juraj , Bader Michael , Unger Thomas , Kintscher Ulrich 
Published: December 2005

AbstractThe angiotensin type 2 (AT2) receptor has been previously demonstrated to exert neuroprotective actions possibly by inducing neuronal cell differentiation involving neurite outgrowth. The nuclear hormone receptor peroxisome proliferator‐activated receptor gamma (PPARγ) is an important transcriptional regulator of cell differentiation. The aim of the present study was to clarify whether PPARγ is involved in AT2‐receptor‐mediated morphological neuronal cell differentiation. To investigate AT2‐receptor‐mediated morphological neuronal cell differentiation, rat pheochromocytoma cells (PC12W cells) expressing AT2 but not AT1 receptors, were stimulated with angiotensin II (Ang II, 100 nmol/L) ± the PPARγ antagonists GW9662 (3 µmol/L) and bisphenol A diglycidyl ether (BADGE, 1 µmol/L), and neurite outgrowth of these cells was assessed. Ang II induced neurite outgrowth by 19 ± 1.6‐fold (p < 0.01). Antagonizing PPARγ activity by GW9662 or BADGE potently blocked Ang II‐induced neurite outgrowth (Ang II + GW9662: 6.6 ± 1.5‐fold,p < 0.05; Ang II + BADGE: 1.3 ± 0.7‐fold,p < 0.01). AT2 receptor activation by Ang II markedly induced mRNA and protein expression of the PPARγ2 isoform and enhanced ligand‐induced PPARγ activity in transactivation assays. In conclusion, the present study demonstrates that Ang II induces PPARγ expression and ligand‐mediated PPARγ activity via AT2 receptor activation, which appears to be a crucial process in AT2 receptor mediated neurite outgrowth. AT2 receptor/PPARγ‐dependent neurite outgrowth may play an important role during neuroprotective processes.
PERK is responsible for the increased phosphorylation of eIF2α and the severe inhibition of protein synthesis after transient global brain ischemia
Authors: Owen Cheri R. , Kumar Rita , Zhang Peichuan , McGrath Barbara C. , Cavener Douglas R. , Krause Gary S. 
Published: December 2005

AbstractReperfusion after global brain ischemia results initially in a widespread suppression of protein synthesis in neurons that is due to inhibition of translation initiation as a result of the phosphorylation of the α‐subunit of eukaryotic initiation factor 2 (eIF2). To address the role of the eIF2α kinase RNA‐dependent protein kinase‐like endoplasmic reticulum kinase (PERK) in the reperfused brain, transgenic mice with a targeted disruption of the Perk gene were subjected to 20 min of forebrain ischemia followed by 10 min of reperfusion. In wild‐type mice, phosphorylated eIF2α was detected in the non‐ischemic brain and its levels were elevated threefold after 10 min of reperfusion. Conversely, there was no phosphorylated eIF2α detected in the non‐ischemic transgenic mice and there was no sizeable rise in phosphorylated eIF2α levels in the forebrain after ischemia and reperfusion. Moreover, there was a substantial rescue of protein translation in the reperfused transgenic mice. Neither group showed any change in total eIF2α, phosphorylated eukaryotic elongation factor 2 or total eukaryotic elongation factor 2 levels. These data demonstrate that PERK is responsible for the large increase in phosphorylated eIF2α and the suppression of translation early in reperfusion after transient global brain ischemia.
Lithium enhances secretion from large dense‐core vesicles in nerve growth factor‐differentiated PC12 cells
Authors: Umbach Joy A. , Zhao Ying , Gundersen Cameron B. 
Published: December 2005

AbstractConsiderable attention has been focused on the therapeutic role of lithium (Li) in bipolar disorders. Although no consensus has emerged, Li presumably influences the behavior of neurons that regulate mood and behavior. Using PC12 cells to study cellular and molecular actions of Li, we previously reported that Li modulates the expression of proteins associated with large dense‐core vesicles (LDCVs; organelles typically containing monoamines, neuropeptides and other cargo proteins). The current investigation indicates that this enhanced expression of LDCV proteins correlates with an altered secretory phenotype in Li‐treated cells. Immunoblotting detects significant increases in the cellular content and secretion of the LDCV cargo proteins chromogranin B and secretogranin II. Amperometry reveals an increase of spike number elicited by K+‐depolarization of Li‐treated cells but no change of spike amplitude or kinetics. Electron microscopy reveals no significant change in LDCV number per unit area in Li‐treated cells. However, there is a significant increase (about 15%) in the diameter of LDCVs after Li. Thus, Li induces changes in the properties of LDCVs that culminate in augmented regulated secretion in nerve growth factor‐differentiated PC12 cells. These results extend our understanding of Li‐dependent changes of cellular function that may be germane to the therapeutic action of Li.
Deficits in dopamine clearance and locomotion in hypoinsulinemic rats unmask novel modulation of dopamine transporters by amphetamine
Authors: Owens W. Anthony , Sevak Rajkumar J. , Galici Ruggero , Chang Xiaoying , Javors Martin A. , Galli Aurelio , France Charles P. , Daws Lynette C. 
Published: December 2005

AbstractInsulin affects brain reward pathways and there is converging evidence that this occurs through insulin regulation of the dopamine (DA) transporter (DAT). In rats made hypoinsulinemic by fasting, synaptosomal DA uptake is reduced. Interestingly, [3H]DA uptake is increased in hypoinsulinemic rats with a history of amphetamine self‐administration. The possibility that amphetamine and insulin act in concert to regulate DAT activity prompted this study. Here we show that [3H]DA uptake, measuredin vitroand clearance of exogenously applied DAin vivo, is significantly reduced in rats made hypoinsulinemic by a single injection of streptozotocin. Strikingly, amphetamine (1.78 mg/kg, given every other day for 8 days) restored DA clearance in streptozotocin‐treated rats but was without effect on DA clearance in saline‐treated rats. Basal locomotor activity of streptozotocin‐treated rats was lower compared to control rats; however, in streptozotocin‐treated rats, hyperlocomotion induced by amphetamine increased over successive amphetamine injections. In saline‐treated rats the locomotor stimulant effect of amphetamine remained stable across the four amphetamine injections. These results provide exciting new evidence that actions of amphetamine on DA neurotransmission are insulin‐dependent and further suggest that exposure to amphetamine may cause long‐lasting changes in DAT function.
Role of NADPH oxidase in the brain injury of intracerebral hemorrhage
Authors: Tang Jiping , Liu Jun , Zhou Changman , Ostanin Dmitry , Grisham Matthew B. , Neil Granger D. , Zhang John H. 
Published: December 2005

AbstractThe major risk factors for intracerebral hemorrhage (ICH) are hypertension and aging. A fundamental mechanism for hypertension‐ and aging‐induced vascular injury is oxidative stress. We hypothesize that oxidative stress has a crucial role in ICH. To test our hypothesis, we used bacterial collagenase to produce ICH in wild‐type C57BL/6 andgp91phoxknockout (gp91phoxKO) mice (deficient in gp91phoxsubunit of the superoxide‐producing enzyme NADPH oxidase). All animals were studied at 20–35 weeks of age, resembling an older patient population. We found that collagenase produced less bleeding ingp91phoxKO mice than wild‐type mice. Total oxidative product was lower ingp91phoxKO mice than in wild‐type mice, both under basal conditions and after ICH. Consistent with the ICH volume, brain edema formation, neurological deficit and a high mortality rate was noted in wild‐type but not ingp91phoxKO mice. This ICH‐induced brain injury in wild‐type mice is associated with enhanced expression of thegp91phoxsubunit of NADPH oxidase. In conclusion, the oxidative stress resulting from activation of NADPH oxidase contributes to ICH induced by collagenase and promotes brain injury.
Molecular and functional characterization of an Na+‐independent choline transporter in rat astrocytes
Authors: Inazu Masato , Takeda Hiroshi , Matsumiya Teruhiko 
Published: December 2005

AbstractIn this study, we examined the molecular and functional characterization of choline uptake into cultured rat cortical astrocytes. Choline uptake into astrocytes showed little dependence on extracellular Na+. Na+‐independent choline uptake was saturable and mediated by a single transport system, with an apparent Michaelis–Menten constant (Km) of 35.7 ± 4.1 µmand a maximal velocity (Vmax) of 49.1 ± 2.0 pmol/mg protein/min. Choline uptake was significantly decreased by acidification of the extracellular medium and by membrane depolarization. Na+‐independent choline uptake was inhibited by unlabeled choline, acetylcholine and the choline analogue hemicholinium‐3. The prototypical organic cation tetrahexylammonium (TEA), and othern‐tetraalkylammonium compounds such as tetrabutylammonium (TBA) and tetrahexylammonium (THA), inhibited Na+‐independent choline uptake, and their inhibitory potencies were in the order THA > TBA > TEA. Various organic cations, such as 1‐methyl‐4‐tetrahydropyridinium (MPP+), clonidine, quinine, quinidine, guanidine,N‐methylnicotinamide, cimetidine, desipramine, diphenhydramine and verapamil, also interacted with the Na+‐independent choline transport system. Corticosterone and 17β‐estradiol, known inhibitors of organic cation transporter 3 (OCT3), did not cause any significant inhibition. However, decynium22, which inhibits OCTs, markedly inhibited Na+‐independent choline uptake. RT‐PCR demonstrated that astrocytes expressed low levels of OCT1, OCT2 and OCT3 mRNA, but the functional characteristics of choline uptake are very different from the known properties of these OCTs. The high‐affinity Na+‐dependent choline transporter, CHT1, is not expressed in astrocytes as evidenced by RT‐PCR. Furthermore, mRNA for choline transporter‐like protein 1 (CTL1), and its splice variants CTL1a and CTL1b, was expressed in rat astrocytes, and the inhibition of CTL1 expression by RNA interference completely inhibited Na+‐independent choline uptake. We conclude that rat astrocytes express an intermediate‐affinity Na+‐independent choline transport system. This system seems to occur through a CTL1 and is responsible for the uptake of choline and organic cations in these cells.
Phosphorylation of tau at serine 416 by Ca2+/calmodulin‐dependent protein kinase II in neuronal soma in brain
Authors: Yamamoto Hideyuki , Hiragami Yukari , Murayama Miyuki , Ishizuka Koko , Kawahara Masahiro , Takashima Akihiko 
Published: December 2005

AbstractIt is well known that tau is a good in vitro substrate for Ca2+/calmodulin‐dependent protein kinase II (CaM kinase II). However, it is not clear at present whether CaM kinase II phosphorylates tau in vivo or not. Serine 416, numbered according to the longest human tau isoform, has been reported to be one of the major phosphorylation sites by CaM kinase II in vitro. In this study, we produced a specific antibody against tau phosphorylated at serine 416 (PS416‐tau). Immunoblot analysis revealed that the antibody reacted with tau in the rat brain extract which was prepared in the presence of protein phosphatase inhibitors. Developmental study indicated that serine 416 was strongly phosphorylated at early developmental stages in rat brain. We examined the localization of PS416‐tau in primary cultured hippocampal neurons and the immortalized GnRH neurons (GT1‐7 cells), which were stably transfected with CaM kinase IIα cDNA. Immunostaining of these cells indicated that tau was phosphorylated mainly in neuronal soma. Interestingly, tau in neuronal soma in Alzheimer's disease (AD) brain was strongly immunostained by the antibody. These results suggest that CaM kinase II is involved in the accumulation of tau in neuronal soma in AD brain.
Lovastatin inhibits the growth and survival pathway of phosphoinositide 3‐kinase/protein kinase B in immortalized rat brain neuroblasts
Authors: Cerezo‐Guisado Maria Isabel , Garcia‐Marin Luis Jesus , Lorenzo Maria Jesus , Bragado Maria Julia 
Published: December 2005

AbstractWe previously showed that lovastatin, an HMG‐CoA reductase inhibitor, suppresses cell growth by inducing apoptosis in rat brain neuroblasts. Our aim was to study intracellular signalling induced by lovastatin in neuroblasts. Lovastatin significantly decreases the phosphoinositide 3‐kinase (PI3‐K) activity in a concentration‐dependent manner. Expression of p85 subunit and its association with phosphotyrosine‐containing proteins are unaffected by lovastatin. Lovastatin decreases protein kinase B (PKB)/Akt phosphorylation, and its downstream effectors, p70S6K and the eukaryotic initiation factor 4E (eIF4E) regulatory protein 1, 4E‐BP1, in a concentration‐dependent manner, and reduces p70S6K expression. Lovastatin effects are fully prevented with mevalonate. Only the highest dose of PI3‐K inhibitors that significantly reduce PI3‐K kinase activity induces apoptosis in neuroblasts but to a lower degree than lovastatin. In summary, this work shows that treatment of brain neuroblasts with lovastatin leads to an inhibition of the main pathway that controls cell growth and survival, PI3‐K/PKB and the subsequent blockade of downstream proteins implicated in the regulation of protein synthesis. This work suggests that inactivation of the antiapoptotic PI3‐K appears insufficient to induce the degree of neuroblasts apoptosis provoked by lovastatin, which must necessarily involve other intracellular pathways. These findings might contribute to elucidate the molecular mechanisms of some statins effects in the central nervous system.
Knowledge Management Using Information Technology: Determinants of Short‐Term Impact on Firm Value*
Authors: Sabherwal Rajiv , Sabherwal Sanjiv 
Published: December 2005

ABSTRACTThe importance of knowledge management (KM) processes for organizational performance is now well recognized. Seeking to better understand the short‐term impact of KM on firm value, this article focuses on public announcements of information technology (IT)‐based KM efforts, and uses cumulative abnormal return (CAR) associated with an announcement as the dependent variable. This article employs a contingency approach, arguing that the KM announcement would have a positive short‐term impact on firm value in some conditions but not in others. Thus, it pursues the following research question: What are the effects of contextual factors on the CAR associated with the announcement of an IT‐based KM effort? Specific hypotheses are proposed based on information‐processing theory, organizational learning theory, the knowledge‐based theory of the firm, and the theory of knowledge creation. These hypotheses link CARs to alignment between industry innovativeness and the KM process, alignment between firm efficiency and the KM process, firm‐specific instability, and firm diversification. The empirical study utilizes secondary data on 89 KM announcements from 1995 to 2002. The results largely support the hypotheses. Overall, this article provides empirical support for the theory‐based arguments, and helps develop a contingency framework of the effectiveness of KM efforts.
Discount Pricing Policies and the Coordination of Decentralized Distribution Systems*
Authors: Wang Qinan 
Published: December 2005

ABSTRACTA challenge of supply chain management is to align the objectives, and hence coordinate the activities, of independent supply chain members. In this study, we approach this problem in a simple way by extending traditional quantity discounts that are based solely on buyers' individual order size to discount policies that are based on both buyers' individual order size and their annual volume. We show that discount policies are able to achieve nearly optimal system profit and, hence, provide effective coordination, for a decentralized two‐echelon distribution system, whereby a supplier sells a product to a group of heterogeneous and independent retailers each facing a downward‐sloping demand curve of its retail price. When buyers are heterogeneous, a critical issue of coordination is to motivate different customers to increase their demand and lot size according to their potential so as to improve profits. We show that market heterogeneity presents an effective discriminating factor for the supplier to segment customers in the design of a coordination mechanism.
Characterization of the Detachable Rho-Dependent Transcription Terminator of the
fimE
Gene in
Escherichia coli
K-12
Authors: Hinde Paul , Deighan Padraig , Dorman Charles J. 
Published: December 2005

ABSTRACT

The
fim
genetic switch in the chromosome of
Escherichia coli
K-12 is an invertible DNA element that harbors the promoter for transcription of the downstream
fim
structural genes and a transcription terminator that acts on the upstream
fimE
regulatory gene. Switches oriented appropriately for structural gene transcription also allow
fimE
mRNA to read through, whereas those in the opposite orientation terminate the
fimE
message. We show here that termination is Rho dependent and is suppressed in a
rho
mutant or by bicyclomycin treatment when
fimE
mRNA is expressed by the
fimE
gene, either from a multicopy recombinant plasmid or in its native chromosomal location. Two
cis-
acting elements within the central portion of the 314-bp invertible DNA switch were identified as contributors to Rho-dependent termination and dissected. These
fim
sequence elements show similarities to well-characterized Rho utilization (
rut
) sites and consist of a
boxA
motif and a C-rich and G-poor region of approximately 40 bp. Deletion of the
boxA
motif alone had only a subtle negative effect on Rho function. However, when this element was deleted in combination with the C-rich, G-poor region, Rho function was considerably decreased. Altering the C-to-G ratio in favor of G in this portion of the switch also strongly attenuated transcription termination. The implications of the existence of a
fimE
-specific Rho-dependent terminator within the invertible switch are discussed in the context of the
fim
regulatory circuit.
luxS-Dependent Gene Regulation inEscherichia coliK-12 Revealed by Genomic Expression Profiling
Authors: Wang Liang , Li Jun , March John C. , Valdes James J. , Bentley William E. 
Published: December 2005

ABSTRACTThe bacterial quorum-sensing autoinducer 2 (AI-2) has received intense interest because the gene for its synthase,luxS, is common among a large number of bacterial species. We have identifiedluxS-controlled genes inEscherichia coliunder two different growth conditions using DNA microarrays. Twenty-three genes were affected byluxSdeletion in the presence of glucose, and 63 genes were influenced byluxSdeletion in the absence of glucose. Minimal overlap among these gene sets suggests the role ofluxSis condition dependent. Under the latter condition, themetEgene, thelsrACDBFGoperon, and the flanking genes of thelsroperon (lsrR,lsrK,tam, andyneE) were among the most significantly induced genes byluxS. TheE. coli lsroperon includes an additional gene,tam, encoding anS-adenosyl-l-methionine-dependent methyltransferase. Also,lsrRandlsrKbelong to the same operon,lsrRK, which is positively regulated by the cyclic AMP receptor protein and negatively regulated by LsrR.lsrKis additionally transcribed by a promoter betweenlsrRandlsrK. Deletion ofluxSwas also shown to affect genes involved in methionine biosynthesis, methyl transfer reactions, iron uptake, and utilization of carbon. It was surprising, however, that so few genes were affected byluxSdeletion in thisE. coliK-12 strain under these conditions. Most of the highly induced genes are related to AI-2 production and transport. These data are consistent with the function of LuxS as an important metabolic enzyme but appear not to support the role of AI-2 as a true signal molecule forE. coliW3110 under the investigated conditions.
Simultaneous Deficiency of both MurA and p60 Proteins Generates a Rough Phenotype inListeria monocytogenes
Authors: Machata Silke , Hain Torsten , Rohde Manfred , Chakraborty Trinad 
Published: December 2005

ABSTRACTWe examined eight spontaneously occurring rough mutants ofListeria monocytogenesfor their ability to express two previously reported autolysins, p60 and MurA. All mutants lack MurA expression and show strongly reduced levels of extracellular p60. One rough strain harbors a variant of the p60 protein with a partially truncated catalytic domain. In seven cases there were shifts in the localization of p60 to the membrane fraction. Mutations within thesecA2gene, encoding an auxiliary protein secretion system paralog, were previously shown to be involved in the smooth-rough phenotypic variation seen withListeriastrains. An isogenic ΔsecA2EGDe deletion strain displays a strong pleiotropic reduction of p60 and MurA, in addition to a large number of secreted and surface proteins. However, we observed no apparent SecA2 dysfunction in several of the investigated strains as determined by direct sequencing of thesecA2gene and complementation of the ΔsecA2mutant with the respective allele cloned from the rough mutant. To determine the gene products required for the smooth-rough transition, we created mutants lacking the individualiapandmurAgenes as well as a ΔiapΔmurAdouble mutant. The double mutant displays a rough phenotype and exhibits many of the properties seen with the ΔsecA2mutant. Our results implicate p60 and MurA as important determinants in controlling the cell shape ofL. monocytogenes. We also identified homologous MurA and SecA2 proteins in otherListeriaspecies. The muramidase in two species,L. innocuaandL. welshimeri, shows activity similar to that of the MurA protein inL. monocytogenes.
Only One of the Five CheY Homologs in
Vibrio cholerae
Directly Switches Flagellar Rotation
Authors: Hyakutake Akihiro , Homma Michio , Austin Melissa J. , Boin Markus A. , Häse Claudia C. , Kawagishi Ikuro 
Published: December 2005

ABSTRACT

Vibrio cholerae
has three sets of chemotaxis (Che) proteins, including three histidine kinases (CheA) and four response regulators (CheY) that are encoded by three
che
gene clusters. We deleted the
cheY
genes individually or in combination and found that only the
cheY3
deletion impaired chemotaxis, reinforcing the previous conclusion that
che
cluster II is involved in chemotaxis. However, this does not exclude the involvement of the other clusters in chemotaxis. In other bacteria, phospho-CheY binds directly to the flagellar motor to modulate its rotation, and CheY overexpression, even without CheA, causes extremely biased swimming behavior. We reasoned that a
V. cholerae
CheY homolog, if it directly controls flagellar rotation, should also induce extreme swimming behavior when overproduced. This was the case for CheY3 (
che
cluster II). However, no other CheY homolog, including the putative CheY (CheY0) protein encoded outside the
che
clusters, affected swimming, demonstrating that these CheY homologs cannot act directly on the flagellar motor. CheY4 very slightly enhanced the spreading of an
Escherichia coli cheZ
mutant in semisolid agar, raising the possibility that it can affect chemotaxis by removing a phosphoryl group from CheY3. We also found that
V. cholerae
CheY3 and
E. coli
CheY are only partially exchangeable. Mutagenic analyses suggested that this may come from coevolution of the interacting pair of proteins, CheY and the motor protein FliM. Taken together, it is likely that the principal roles of
che
clusters I and III as well as
cheY0
are to control functions other than chemotaxis.