(Stroke. 2001;32:184.)
© 2001 American Heart Association, Inc.
Original Contributions |
Gene Transfer of Extracellular Superoxide Dismutase Increases Superoxide Dismutase Activity in Cerebrospinal Fluid
From the Departments of Internal Medicine and Pharmacology, Cardiovascular Center, and Radiation Research Laboratory (L.W.O.), University of Iowa College of Medicine, Iowa City.
Correspondence to Donald D. Heistad, MD, Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, IA 52242. E-mail donald-heistad{at}uiowa.edu
Background and Purpose—Copper-zinc superoxide dismutase (CuZnSOD) is expressed intracellularly, while extracellular SOD (EC-SOD) is released from cells. The purpose of this study was to determine whether gene transfer of CuZnSOD increases SOD activity predominantly in tissues, and gene transfer of EC-SOD increases SOD activity in cerebrospinal fluid (CSF). We also determined whether heparin or dextran sulfate releases EC-SOD into CSF.
Methods—We injected recombinant adenoviruses expressing EC-SOD (AdEC-SOD), CuZnSOD (AdCuZnSOD), or ß-galactosidase (Adß-gal) into the cisterna magna of rabbits.
Results—Total SOD activity in CSF was 39±11 U/mL (mean±SE) before virus injection. Three days later, total SOD activity in CSF increased to 148±22 U/mL after AdEC-SOD and 92±10 U/mL after AdCuZnSOD (P<0.05 versus AdEC-SOD), with no change after Adß-gal (49±5 U/mL). EC-SOD protein was detected in CSF after AdEC-SOD but not AdCuZnSOD or Adß-gal. Injection of heparin or dextran sulfate into the cisterna magna increased total SOD activity 27-fold and 32-fold over basal values, respectively, in CSF of rabbits that received AdEC-SOD. In contrast to effects in CSF, total SOD activity in basilar artery and meninges was significantly higher after AdCuZnSOD and tended to be higher after AdEC-SOD than after Adß-gal.
Conclusions—We have developed a method for intracranial gene transfer of CuZnSOD and EC-SOD. After gene transfer, CuZnSOD was expressed mainly in tissues, and EC-SOD was released into the CSF, especially after injection of heparin or dextran sulfate. Gene transfer of different isoforms of SOD may be useful in studies of cerebral vascular physiology and pathophysiology.
Editorial Comment
Neurosurgical Laboratories, Stanford University, Stanford, California
This article has been cited by other articles:
 |
|
 |
|
  J. Kitayama, C. Yi, F. M. Faraci, and D. D. Heistad Modulation of Dilator Responses of Cerebral Arterioles by Extracellular Superoxide Dismutase Stroke, November 1, 2006; 37(11): 2802 - 2806. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamaguchi, C. Zhou, D. D. Heistad, Y. Watanabe, and J. H. Zhang Gene Transfer of Extracellular Superoxide Dismutase Failed to Prevent Cerebral Vasospasm After Experimental Subarachnoid Hemorrhage Stroke, November 1, 2004; 35(11): 2512 - 2517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. J. Bivalacqua, J. S. Armstrong, J. Biggerstaff, A. B. Abdel-Mageed, P. J. Kadowitz, W. J. G. Hellstrom, and H. C. Champion Gene transfer of extracellular SOD to the penis reduces O Am J Physiol Heart Circ Physiol, April 1, 2003; 284(4): H1408 - H1421. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Watanabe, Y. Chu, J. J. Andresen, H. Nakane, F. M. Faraci, and D. D. Heistad Gene Transfer of Extracellular Superoxide Dismutase Reduces Cerebral Vasospasm After Subarachnoid Hemorrhage Stroke, February 1, 2003; 34(2): 434 - 440. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. P. Didion, M. J. Ryan, L. A. Didion, P. E. Fegan, C. D. Sigmund, and F. M. Faraci Increased Superoxide and Vascular Dysfunction in CuZnSOD-Deficient Mice Circ. Res., November 15, 2002; 91(10): 938 - 944. [Abstract] [Full Text] [PDF]
|
|