This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Nakane, H. Articles by Chan, P. H. Search for Related Content PubMed PubMed Citation Articles by Nakane, H. Articles by Chan, P. H. Related Collections Brain Circulation and Metabolism Gene therapy Oxidant stress Other Vascular biology

(Stroke. 2001;32:184.)
© 2001 American Heart Association, Inc.

Original Contributions

Gene Transfer of Extracellular Superoxide Dismutase Increases Superoxide Dismutase Activity in Cerebrospinal Fluid

Hiroshi Nakane, MD; Yi Chu, PhD; Frank M. Faraci, PhD; Larry W. Oberley, PhD Donald D. Heistad, MD

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

Pak H. Chan, PhD, Guest Editor

Neurosurgical Laboratories, Stanford University, Stanford, California

This article has been cited by other articles:

				M. L.T. Teoh, M. P. Fitzgerald, L. W. Oberley, and F. E. Domann Overexpression of Extracellular Superoxide Dismutase Attenuates Heparanase Expression and Inhibits Breast Carcinoma Cell Growth and Invasion Cancer Res., August 1, 2009; 69(15): 6355 - 6363. [Abstract] [Full Text] [PDF]

				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 O2−{middle dot} and improves erectile function in aged rats 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]

				C. M. Maier and P. H. Chan Book Review: Role of Superoxide Dismutases in Oxidative Damage and Neurodegenerative Disorders Neuroscientist, August 1, 2002; 8(4): 323 - 334. [Abstract] [PDF]