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Published online before print July 14, 2009
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.0708454

Received for publication July 31, 2008.
Revised April 10, 2009.
Accepted for publication May 8, 2009.

Article

Stanniocalcin-1 suppresses superoxide generation in macrophages through induction of mitochondrial UCP2

Yanlin Wang *, Luping Huang *, Maen Abdelrahim {dagger}, Qingsong Cai *, Anh Truong *, Roger Bick {ddagger}, Brian Poindexter {ddagger}, and David Sheikh-Hamad *@

*Division of Nephrology, Department of Medicine, Baylor College of Medicine, Houston, Texas, USA;{dagger}Cancer Research Institute, MD Anderson Cancer Center Orlando, Orlando, Florida, USA; and{ddagger}Department of Pathology, University of Texas Health Sciences Center, Houston, Texas, USA

@ To whom correspondence should be addressed. E-mail: sheikh{at}bcm.tmc.edu.


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Abstract

Mammalian STC1 decreases the mobility of macrophages and diminishes their response to chemokines. In the current experiments, we sought to determine the impact of STC1 on energy metabolism and superoxide generation in mouse macrophages. STC1 decreases ATP level in macrophages but does not affect the activity of respiratory chain complexes I–IV. STC1 induces the expression of mitochondrial UCP2, diminishing mitochondrial membrane potential and superoxide generation; studies in UCP2 null and gp91phox null macrophages suggest that suppression of superoxide by STC1 is UCP2-dependent yet is gp91phox-independent. Furthermore, STC1 blunts the effects of LPS on superoxide generation in macrophages. Exogenous STC1 is internalized by macrophages within 10 min and localizes to the mitochondria, suggesting a role for circulating and/or tissue-derived STC1 in regulating macrophage function. STC1 induces arrest of the cell cycle at the G1 phase and reduces cell necrosis and apoptosis in serum-starved macrophages. Our data identify STC1 as a key regulator of superoxide generation in macrophages and suggest that STC1 may profoundly affect the immune/inflammatory response.

Key Words: monocytes • uncoupling proteins • free radicals • apoptosis • lipopolysaccharide • gene regulation.




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 Am. J. Physiol. Renal Physiol.Home page
D. Sheikh-Hamad
Mammalian stanniocalcin-1 activates mitochondrial antioxidant pathways: new paradigms for regulation of macrophages and endothelium
Am J Physiol Renal Physiol, February 1, 2010; 298(2): F248 - F254.
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