Molecular Analysis of Cocaine-Induced Endothelial Dysfunction: Role of Endothelin-1 and Nitric Oxide

Pradhan, Leena; Mondal, Debasis; Chandra, Surabhi; Ali, Mussa; Agrawal, Krishna C.

doi:10.1007/s12012-008-9025-z

Cited by 56 publications

(51 citation statements)

References 44 publications

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“…The endothelin signaling pathway was also identified by PANTHER when cocaine‐specific genes harboring putatively novel L1s was used as input (Table 2C). An acute effect of cocaine is the release of endothelin‐1 (ET‐1), a potent vasoconstrictor, with elevated levels observed within 6 hours and normal levels returning by 24 hours (Pradhan, Mondal, Chandra, Ali, & Agrawal, 2008). Activation of the ET A R of ET‐1 decreases NO, a vasodilator, production by suppressing eNOS expression.…”

Section: Discussionmentioning

confidence: 99%

Reading LINEs within the cocaine addicted brain

Doyle

Doucet-O’Hare²,

Hammond

et al. 2017

Brain and Behavior

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IntroductionLong interspersed element (LINE)‐1 (L1) is a type of retrotransposon capable of mobilizing into new genomic locations. Often studied in Mendelian diseases or cancer, L1s may also cause somatic mutation in the developing central nervous system. Recent reports showed L1 transcription was activated in brains of cocaine‐treated mice, and L1 retrotransposition was increased in cocaine‐treated neuronal cell cultures. We hypothesized that the predisposition to cocaine addiction may result from inherited L1s or somatic L1 mobilization in the brain.MethodsPostmortem medial prefrontal cortex (mPFC) tissue from 30 CA and 30 control individuals was studied. An Alexafluor488‐labeled NeuN antibody and fluorescence activated nuclei sorting were used to separate neuronal from non‐neuronal cell nuclei. L1s and their 3' flanking sequences were amplified from neuronal and non‐neuronal genomic DNA (gDNA) using L1‐seq. L1 DNA libraries from the neuronal gDNA were sequenced on an Illumina HiSeq2000. Sequences aligned to the hg19 human genome build were analyzed for L1 insertions using custom “L1‐seq” bioinformatics programs.ResultsPreviously uncataloged L1 insertions, some validated by PCR, were detected in neurons from both CA and control brain samples. Steady‐state L1 mRNA levels in CA and control mPFC were also assessed. Gene ontology and pathway analyses were used to assess relationships between genes putatively disrupted by novel L1s in CA and control individuals. L1 insertions in CA samples were enriched in gene ontologies and pathways previously associated with CA.ConclusionsWe conclude that neurons in the mPFC harbor L1 insertions that have the potential to influence predisposition to CA.

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Section: Discussionmentioning

confidence: 99%

Reading LINEs within the cocaine addicted brain

Doyle

Doucet-O’Hare²,

Hammond

et al. 2017

Brain and Behavior

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“…Striatal miR-212 decreases responsiveness to the motivational properties of cocaine by markedly amplifying the stimulatory effects of the drug on CREB signaling (Hollander et al, 2010). Acute exposure to cocaine singifcantly increases endothelin receptor type A (EDNRA) within 6-12 h (Pradhan et al, 2008). Coinfusion of cocaine with the endothelin receptor antagonist PD145065 prevented the cocaine induced spasm (Fandino et al, 2003).…”

Section: Discussionmentioning

confidence: 99%

Functions of microRNA in response to cocaine stimulation

Wang²,

Lv³

et al. 2013

Genet. Mol. Res.

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ABSTRACT. MicroRNAs (miRNAs) are a type of non-protein-coding single-stranded RNA, which are typically 20-25 nt in length. miRNAs play important roles in various biological processes, including development, cell proliferation, differentiation, and apoptosis. We aimed to detect the miRNA response to cocaine stimulations and their target genes. Using the miRNA expression data GSE21901 downloaded from the Gene Expression Omnibus database, we screened out the differentially expressed miRNA after short-term (1 h) and longer-term (6 h) cocaine stimulations based on the fold change >1.2. Target genes of differentially expressed miRNAs were retrieved from TargetScan database with the context score -0.3. Functional annotation enrichment analysis was performed for all the target genes with DAVID. A total of 121 differentially expressed miRNAs between the 1-h treatment and the control samples, 58 between the 6-h treatment and the control samples, and 69 between the 1-h and the 6-h treatment samples. Among them, miR-212 results of particular interest, since its expression level was constantly elevated responding to cocaine treatment. After functional and pathway annotations of target genes, we proved that miR-212 was a critical element in cocaine-addiction, because of its involvement in regulating several important cell cycle events. The results may pave the way for further understanding the regulatory mechanisms of cocaine-

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“…Entre los elementos que determinan el inicio y progresión del daño vascular aterosclerótico la disfunción endotelial juega un papel fundamental 11 . Evidencia obtenida de estudios in vitro y en modelos animales demuestra que la cocaína induce disfunción de las células endoteliales 12 . En usuarios crónicos, hemos observado la existencia de disfunción endotelial importante demostrada por aumento signifi cativo de esas células circulantes y niveles elevados de marcadores solubles de daño/activación de la célula endotelial 13 .…”

Section: Fisiopatologíaunclassified