Am J Physiol Cell Physiol Ad Instruments
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (November 2, 2005). doi:10.1152/ajpcell.00499.2005
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
290/4/C964    most recent
00499.2005v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Cheranov, S. Y
Right arrow Articles by Jaggar, J. H
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Cheranov, S. Y
Right arrow Articles by Jaggar, J. H
Submitted on October 3, 2005
Accepted on October 31, 2005

TNF-{alpha} Dilates Cerebral Arteries via NAD(P)H Oxidase-Dependent Ca2+Spark Activation

Sergey Y Cheranov1 and Jonathan H Jaggar1*

1 Physiology, University of Tennessee, Memphis, TN, USA

* To whom correspondence should be addressed. E-mail: jjaggar{at}physio1.utmem.edu.

Expression of Tumor Necrosis Factor alpha (TNF-{alpha}), a pleiotropic cytokine, is elevated during stroke and cerebral ischemia. TNF-{alpha} regulates arterial diameter, although mechanisms mediating this effect are unclear. Here, we tested the hypothesis that TNF-{alpha} regulates the diameter of resistance-size (~150 µm diameter) cerebral arteries by modulating local and global intracellular calcium (Ca2+) signals in smooth muscle cells. Laser-scanning confocal imaging revealed that TNF-{alpha} increased Ca2+ spark and Ca2+ wave frequency, but reduced global Ca2+ concentration ([Ca2+]i) in smooth muscle cells of intact arteries. TNF-{alpha} elevated reactive oxygen species (ROS) in smooth muscle cells of intact arteries and this was prevented by apocynin or diphenyleneiodonium (DPI), NAD(P)H oxidase blockers, but was unaffected by inhibitors of other ROS generating enzymes. In voltage-clamped (-40 mV) cells, TNF-{alpha} increased the frequency and amplitude of Ca2+ spark-induced large-conductance Ca2+-activated potassium (KCa) channel transients ~1.7-fold and ~1.4-fold, respectively. TNF-{alpha}-induced transient KCa current activation was reversed by apocynin or MnTMPyP, a membrane-permeant antioxidant, and prevented by intracellular dialysis of catalase. TNF-{alpha} induced reversible and similar amplitude dilations in either endothelium-intact or -denuded pressurized (60 mm Hg) cerebral arteries. MnTMPyP, thapsigargin, a sarcoplasmic reticulum Ca2+ ATP-ase blocker that inhibits Ca2+ sparks, and iberiotoxin, a KCa channel blocker, reduced TNF-{alpha}-induced vasodilations to between 15 and 33% of control. In summary, data indicate that TNF-{alpha} activates NAD(P)H oxidase, resulting in an increase in intracellular H2O2 that stimulates Ca2+ sparks and transient KCa currents, leading to a reduction in global [Ca2+]i, and vasodilation.




This article has been cited by other articles:


Home page
 J Child NeurolHome page
A. J. du Plessis
The Role of Systemic Hemodynamic Disturbances in Prematurity-Related Brain Injury
J Child Neurol, September 1, 2009; 24(9): 1127 - 1140.
[Abstract] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
S. Basuroy, S. Bhattacharya, C. W. Leffler, and H. Parfenova
Nox4 NADPH oxidase mediates oxidative stress and apoptosis caused by TNF-{alpha} in cerebral vascular endothelial cells
Am J Physiol Cell Physiol, March 1, 2009; 296(3): C422 - C432.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
S. Jin, R. M. Ray, and L. R. Johnson
TNF-{alpha}/cycloheximide-induced apoptosis in intestinal epithelial cells requires Rac1-regulated reactive oxygen species
Am J Physiol Gastrointest Liver Physiol, April 1, 2008; 294(4): G928 - G937.
[Abstract] [Full Text] [PDF]

Home page
 Arch. Dis. Child. Fetal Neonatal Ed.Home page
O Khwaja and J J Volpe
Pathogenesis of cerebral white matter injury of prematurity
Arch. Dis. Child. Fetal Neonatal Ed., March 1, 2008; 93(2): F153 - F161.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
G. Zhao, A. Adebiyi, Q. Xi, and J. H. Jaggar
Hypoxia reduces KCa channel activity by inducing Ca2+ spark uncoupling in cerebral artery smooth muscle cells
Am J Physiol Cell Physiol, June 1, 2007; 292(6): C2122 - C2128.
[Abstract] [Full Text] [PDF]

Home page
 Physiol. Rev.Home page
K. Bedard and K.-H. Krause
The NOX Family of ROS-Generating NADPH Oxidases: Physiology and Pathophysiology
Physiol Rev, January 1, 2007; 87(1): 245 - 313.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
A. Li, A. Adebiyi, C. W. Leffler, and J. H. Jaggar
KCa channel insensitivity to Ca2+ sparks underlies fractional uncoupling in newborn cerebral artery smooth muscle cells
Am J Physiol Heart Circ Physiol, September 1, 2006; 291(3): H1118 - H1125.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
C. G. Sobey and A. A. Miller
Radicals spark interest in cerebral vasodilator mechanisms. Focus on "TNF-{alpha} dilates cerebral arteries via NAD(P)H oxidase-dependent Ca2+ spark activation"
Am J Physiol Cell Physiol, April 1, 2006; 290(4): C950 - C951.
[Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.