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Paper Information

Journal:   ARCHIVES OF IRANIAN MEDICINE   January 2003 , Volume 6 , Number 1; Page(s) 49 To 53.
 
Paper: 

ROLE OF CYTOSKELETAL STRUCTURE IN MODULATION OF INTESTINAL PERMEABILITY

 
 
Author(s):  FARHADI ASHKAN*, BANAN A., KESHAVARZIAN A.
 
* DIVISION OF DIGESTIVE DISEASES, DEPARTMENT OF INTERNAL MEDICINE, RUSH UNIVERSITY MEDICAL CENTER1725 W .HARRISON SUITE 206,CHICAGO,IL 60612
 
Abstract: 
The intestine contains the largest interface between man and his environment; thus, ‎the intestinal barrier could be a key factor in health and disease states. This barrier is a ‎highly selective gatekeeper that permits the passage of nutrients and prevents the ‎penetration of harmful bacterial products and dietary antigens. The intestinal barrier is ‎composed of immunological and non immunological compartments and the latter part ‎is made up of multilayered structural and functional components. The intestinal ‎epithelium and its paracellular tight junctions appear to be the key for integrity of this ‎barrier. The cytoskeletal assembly is essential for maintaining epithelial structure, ‎transport, and functional integrity, but is also pivotal for integrity of the paracellular ‎pathway, especially the tight junction complex. Actin and microtubules are two ‎cytoskeletal filaments that play key roles in regulation and maintenance of the ‎intestinal barrier. Various noxious agents such as ethanol and/or oxidants can induce ‎cytoskeletal damage and disruption of barrier integrity. The injurious effects of these ‎compounds are mediated through upregulation and activation of inducible nitric oxide ‎synthase (iNOS) and the resultant NO overproduction and nitration and oxidation of ‎actin and tubulin. Oxidized cytoskeletal proteins result in deploymerization of ‎cytoskeletal filaments, cytoskeletal disassembly and disarray and eventually ‎disruption of barrier function. The disrupted barrier can initiate or perpetuate an ‎inflammatory cascade that will result in intestinal mucosal injury and inflammatory ‎bowel disease flare-up. There are several lines of repair/defense that help to brake this ‎inflammatory cascade, reestablish barrier integrity and thus limit or terminate mucosal ‎injury. One of these lines of defense is mediated through protecting factors such as ‎epidermal growth factor, which prevents ethanol-induced and oxidative damage to the ‎gastrointestinal epithelium‏.‏
 
Keyword(s): ACTIN, CYTOSKELETAL STRUCTURE, INTESTINAL PERMEABILITY, TUBULIN
 
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