Document Detail

Increase of metabolic activity and disruption of normal contractile protein distribution by bilirubin oxidation products in vascular smooth-muscle cells.
MedLine Citation:
PMID:  15035287     Owner:  NLM     Status:  MEDLINE    
OBJECT: Cerebral vasospasm is a common cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). Previous research has shown that bilirubin oxidation products (BOXes) are present in the cerebral spinal fluid in patients with SAH-induced cerebral vasospasm and can contribute to vasoconstriction and vasospasm in vitro and in vivo. The events leading to cerebral vasospasm are not understood; however, one component of the occlusion may be due to vascular remodeling. In this study the authors have investigated the actions of BOXes, okadaic acid ([OA], a phosphatase inhibitor), and phorbol-12 myristate-13 acetate ([PMA], a protein kinase activator) on vascular smooth-muscle cell (VSMC) morphology and metabolism. METHODS: Immunohistochemical analysis was performed to assess VSMC morphology and alpha-smooth-muscle actin (alphaSMA) distribution following the application of BOXes, OA, or PMA. Changes in the level of lactate dehydrogenase (LDH) release and oxidative metabolism were also measured. The BOXes, OA, or PMA caused VSMCs to change their shape and exhibit altered alphaSMA distribution. These treatments increased LDH release (p < 0.05), which is an index of increased cell stress. Oxidative metabolism significantly increased at low and high doses of BOXes, that is, 143 +/- 8.5% and 180 +/- 11.8%, respectively (p < 0.0001). Both PMA and OA also caused a significant increase in metabolism. CONCLUSIONS: The authors concluded that BOXes, OA, and PMA alter VSMC morphology and metabolic activity, events that have been observed during vascular remodeling. Although the mechanism remains unclear, the results indicate that BOXes may play a role in the vascular remodeling that occurs following aneurysmal SAH.
Melissa A Lyons; Rakesh Shukla; Kejun Zhang; Gail J Pyne; Meha Singh; Susan J Biehle; Joseph F Clark
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Journal of neurosurgery     Volume:  100     ISSN:  0022-3085     ISO Abbreviation:  J. Neurosurg.     Publication Date:  2004 Mar 
Date Detail:
Created Date:  2004-03-23     Completed Date:  2004-04-22     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0253357     Medline TA:  J Neurosurg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  505-11     Citation Subset:  AIM; IM    
Department of Neurology, College of Medicine, University of Cincinnati, Ohio 45267, USA.
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MeSH Terms
Carrier Proteins / metabolism
Contractile Proteins / metabolism*
Disease Models, Animal
Intracellular Signaling Peptides and Proteins*
L-Lactate Dehydrogenase / metabolism
Muscle, Smooth, Vascular / metabolism*,  pathology
Okadaic Acid / metabolism
Oxidoreductases Acting on CH-CH Group Donors / metabolism*
Proteins / metabolism
Subarachnoid Hemorrhage / complications
Tetradecanoylphorbol Acetate / analogs & derivatives*,  metabolism
Vasospasm, Intracranial / etiology,  metabolism*,  pathology*
Grant Support
Reg. No./Substance:
0/Carrier Proteins; 0/Contractile Proteins; 0/Intracellular Signaling Peptides and Proteins; 0/Proteins; 0/protein phosphatase inhibitor-1; 0/protein phosphatase inhibitor-2; 16561-29-8/Tetradecanoylphorbol Acetate; 56937-68-9/phorbolol myristate acetate; 78111-17-8/Okadaic Acid; EC Dehydrogenase; EC 1.3.-/Oxidoreductases Acting on CH-CH Group Donors; EC oxidase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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