Linked Life Data

19120127

Source:http://linkedlifedata.com/resource/pubmed/id/19120127

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2009-1-5
pubmed:abstractText
Patients with panic disorder provide a clinical model of stress. On a "good day," free from a panic attack, they show persistent stress-related changes in sympathetic nerve biology, including abnormal sympathetic nerve single-fiber firing ("salvos" of multiple firing within a cardiac cycle) and release of epinephrine as a cotransmitter. The coreleased epinephrine perhaps originates from in situ synthesis by phenylethanolamine N-methyltransferase (PNMT). In searching for biological evidence that essential hypertension is caused by mental stress--a disputed proposition--we note parallels with panic disorder, which provides an explicit clinical model of stress: (1) There is clinical comorbidity; panic disorder prevalence is increased threefold in essential hypertension. (2) For both, epinephrine cotransmission is present in sympathetic nerves. (3) In panic disorder and essential hypertension, but not in health, single-fiber sympathetic nerve firing salvos occur. (4) Tissue nerve growth factor is increased in both conditions (nerve growth factor is a stress reactant). (5) There is induction of PNMT in sympathetic nerves. Essential hypertension exhibits a further manifestation of mental stress: there is activation of noradrenergic brain stem neurons projecting to the hypothalamus and amygdala. These pathophysiological findings strongly support the view that chronic mental stress is important in the pathogenesis of essential hypertension. A hypothesis now under test is whether in both disorders, under prevailing conditions of ongoing stress, PNMT induced in sympathetic nerves acts as a DNA methylase, causing the norepinephrine transporter (NET) gene silencing that is present in both conditions. PNMT can have an intranuclear distribution, binding to DNA. We have demonstrated that the reduced neuronal noradrenaline reuptake present in both disorders does have an epigenetic mechanism, with demonstrable reduction in the abundance of the transporter protein, the NET gene silencing being associated with DNA binding by the methylation-related inhibitory transcription factor MeCP2.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1749-6632
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
1148
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
338-48
pubmed:meshHeading
pubmed-meshheading:19120127-Action Potentials, pubmed-meshheading:19120127-Biological Markers, pubmed-meshheading:19120127-DNA Methylation, pubmed-meshheading:19120127-Epigenesis, Genetic, pubmed-meshheading:19120127-Epinephrine, pubmed-meshheading:19120127-Gene Silencing, pubmed-meshheading:19120127-Humans, pubmed-meshheading:19120127-Hydrocortisone, pubmed-meshheading:19120127-Hypertension, pubmed-meshheading:19120127-Methyl-CpG-Binding Protein 2, pubmed-meshheading:19120127-Nerve Growth Factor, pubmed-meshheading:19120127-Neurons, pubmed-meshheading:19120127-Norepinephrine, pubmed-meshheading:19120127-Norepinephrine Plasma Membrane Transport Proteins, pubmed-meshheading:19120127-Panic Disorder, pubmed-meshheading:19120127-Phenylethanolamine N-Methyltransferase, pubmed-meshheading:19120127-Stress, Psychological, pubmed-meshheading:19120127-Sympathetic Nervous System
pubmed:year
2008
pubmed:articleTitle
Human sympathetic nerve biology: parallel influences of stress and epigenetics in essential hypertension and panic disorder.
pubmed:affiliation
Baker Heart Research Institute, Melbourne, Australia. murray.esler@baker.edu.au
pubmed:publicationType
Journal Article