Linked Life Data

12906918

Source:http://linkedlifedata.com/resource/pubmed/id/12906918

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-8-8
pubmed:abstractText
Dioxin is known to cause many toxic effects that vary greatly in different tissues, ages, genders, and species. In this review, an attempt has been made to sort out major signaling pathways involved in the expression of the toxicities of dioxin. The major strategy adopted in analyzing its major signaling pathways is to view the toxic actions of dioxin as the result of the Ah receptor-mediated expression of a major cellular emergency stress response signal. Evidence pointing to the similarities between the symptoms of poisoning by dioxin and those produced by chronic administration of typical stressors, particularly lipopolysaccharides (LPS), bacterial endotoxins, has been assembled and analyzed. The common symptoms are wasting syndrome, atherosclerosis, fatty liver, and thymic atrophy. On the other hand, oxidative stress caused by cytochrome P450 induction is one of the typical stresses of dioxin poisoning, but not LPS poisoning. One of the major means through which dioxin triggers stress responses via "stress-activated kinase pathways" is stimulation of the cellular production of cytokines/autocrines, particularly growth factors. In the case of hepatocytes for instance, transforming growth factor-alpha plays a pivotal role in the dioxin-induced activation of the epidermal growth factor receptor and the extracellular signal-related kinase pathway, which acts as a signal to suppress apoptosis induced by cellular stress. These observations as well as additional experimental data support the idea that one of the major functions of the Ah receptor could be the elicitation of cellular stress response reactions. Another key point in understanding the toxic action of dioxin is that, unlike other cases of stressors, dioxin signaling becomes chronically sustained because of its extreme persistence in the human body, its half-life of 7-10 years, and its selective accumulation in fatty target tissues.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
66
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
527-40
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
On the significance of the role of cellular stress response reactions in the toxic actions of dioxin.
pubmed:affiliation
Department of Environmental Toxicology, University of California, One Shields Avenue, Davis, CA, USA. fmatsumura@ucdavis.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Review