Subcellular distribution of dolichol phosphate

originalFil: Dallner, Gustav. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Behrens, Nicolás H.. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Parodi, Armando José A.. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaFil: Leloir, Luis Federico. Instituto de Investigaciones Bioquímicas Fundación Campomar; ArgentinaBlanco y negro3 páginas en pdfLFL-PI-O-ART. Artículos científicosUnidad documental simpleAR-HYL-201

Inhibitory Role of Inducible cAMP Early Repressor (ICER) in Methamphetamine-Induced Locomotor Sensitization

BACKGROUND: The inducible cyclic adenosine monophosphate (cAMP) early repressor (ICER) is highly expressed in the central nervous system and functions as a repressor of cAMP response element-binding protein (CREB) transcription. The present study sought to clarify the role of ICER in the effects of methamphetamine (METH). METHODS AND FINDINGS: We tested METH-induced locomotor sensitization in wildtype mice, ICER knockout mice, and ICER I-overexpressing mice. Both ICER wildtype mice and knockout mice displayed increased locomotor activity after continuous injections of METH. However, ICER knockout mice displayed a tendency toward higher locomotor activity compared with wildtype mice, although no significant difference was observed between the two genotypes. Moreover, compared with wildtype mice, ICER I-overexpressing mice displayed a significant decrease in METH-induced locomotor sensitization. Furthermore, Western blot analysis and quantitative real-time reverse transcription polymerase chain reaction demonstrated that ICER overexpression abolished the METH-induced increase in CREB expression and repressed cocaine- and amphetamine-regulated transcript (CART) and prodynorphin (Pdyn) expression in mice. The decreased CART and Pdyn mRNA expression levels in vivo may underlie the inhibitory role of ICER in METH-induced locomotor sensitization. CONCLUSIONS: Our data suggest that ICER plays an inhibitory role in METH-induced locomotor sensitization

Increased RNA synthesis in nuclei isolated from rat liver tissue slices incubated with cyclic adenosine 3',5'-monophosphate or glucagon

Incubation of rat liver tissue slices with cyclic adenosine 3',5'-monophosphate (cyclic AMP) for 30 min results in a dose-dependent increase in RNA synthesizing capacity of nuclei prepared from these slices, with a doubling of synthetic rate observed at 10-7 cyclic AMP. The cyclic AMP effect is observed when RNA polymerase activity is measured either in the presence of Mg2+ and low ionic strength, or Mn2+ and high ionic strength. Experiments employing saturating amounts of exogenous bacterial RNA polymerase suggest that the cyclic AMP-induced stimulation occurs primarily at the level of template activity. Other cyclic nucleotides tested in the same manner are ineffective in stimulating RNA synthesis by tissue slice nuclei. In addition to cyclic AMP, adenosine 5'-monophosphate (5'-AMP) consistently produced small increases in nuclear RNA synthesis although never of the magnitude seen with the cyclic nucleotide.An increased capacity for RNA synthesis is also seen in nuclei isolated from liver slices incubated with glucagon at concentrations from 0.5 [mu]g/ml to 50 [mu]g/ml. A maximal stimulation of approximately twofold occurs at a glucagon concentration of 1.0 [mu]g/ml. Liver slices incubated with optimal concentrations of cyclic AMP and glucagon simultaneously show that the effects of the two agents on RNA synthesis are not additive.The results indicate that cyclic AMP at physiological concentrations can stimulate RNA synthetic capacity in vitro, and that the effect mimics a similar response to glucagon. Since it is known that glucagon causes an increase in liver concentrations of cyclic AMP and a subsequent induction of some liver enzymes, it is suggested that cyclic AMP-mediated control of RNA synthesis may be involved in such regulation.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/33774/1/0000026.pd

Mitochondrial Bioenergetic Alterations in Mouse Neuroblastoma Cells Infected with Sindbis Virus: Implications to Viral Replication and Neuronal Death

The metabolic resources crucial for viral replication are provided by the host. Details of the mechanisms by which viruses interact with host metabolism, altering and recruiting high free-energy molecules for their own replication, remain unknown. Sindbis virus, the prototype of and most widespread alphavirus, causes outbreaks of arthritis in humans and serves as a model for the study of the pathogenesis of neurological diseases induced by alphaviruses in mice. In this work, respirometric analysis was used to evaluate the effects of Sindbis virus infection on mitochondrial bioenergetics of a mouse neuroblastoma cell lineage, Neuro 2a. The modulation of mitochondrial functions affected cellular ATP content and this was synchronous with Sindbis virus replication cycle and cell death. At 15 h, irrespective of effects on cell viability, viral replication induced a decrease in oxygen consumption uncoupled to ATP synthesis and a 36% decrease in maximum uncoupled respiration, which led to an increase of 30% in the fraction of oxygen consumption used for ATP synthesis. Decreased proton leak associated to complex I respiration contributed to the apparent improvement of mitochondrial function. Cellular ATP content was not affected by infection. After 24 h, mitochondria dysfunction was clearly observed as maximum uncoupled respiration reduced 65%, along with a decrease in the fraction of oxygen consumption used for ATP synthesis. Suppressed respiration driven by complexes I- and II-related substrates seemed to play a role in mitochondrial dysfunction. Despite the increase in glucose uptake and glycolytic flux, these changes were followed by a 30% decrease in ATP content and neuronal death. Taken together, mitochondrial bioenergetics is modulated during Sindbis virus infection in such a way as to favor ATP synthesis required to support active viral replication. These early changes in metabolism of Neuro 2a cells may form the molecular basis of neuronal dysfunction and Sindbis virus-induced encephalitis

Molecular Changes in Opioid Addiction: The Role of Adenylyl Cyclase and cAMP/PKA System

For centuries, opiate analgesics have had a considerable presence in the treatment of moderate to severe pain. While effective in providing analgesia, opiates are notorious in exerting many undesirable adverse reactions. The receptor targets and the intracellular effectors of opioids have largely been identified. Furthermore, much of the mechanisms underlying the development of tolerance, dependence, and withdrawal have been delineated. Thus, there is a focus on developing novel compounds or strategies in mitigating or avoiding the development of tolerance, dependence, and withdrawal. This review focuses on the adenylyl cyclase and cyclic adenosine 3,5-monophosphate (cAMP)/protein kinase A (AC/cAMP/PKA) system as the central player in mediating the acute and chronic effects of opioids. This chapter also reviews the neuronal adaptive changes in the locus coeruleus, amygdala, periaqueductal gray, and ventral tegmental area induced by acute and chronic actions of opioid because these neuronal adaptive changes in these regions may underlie the behavioral changes observed in opiate users and abusers