HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

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 Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Angelova, M. Articles by Voelter, W. Search for Related Content PubMed PubMed Citation Articles by Angelova, M. Articles by Voelter, W. Agricola Articles by Angelova, M. Articles by Voelter, W.

A novel glycosylated Cu/Zn-containing superoxide dismutase: production and potential therapeutic effect

Institute of Microbiology, Bulgarian Academy of Sciences, 26 Academician G. Bonchev, 1113 Sofia, Bulgaria¹
Institute of Organic Chemistry, Bulgarian Academy of Sciences, 9 Academician G. Bonchev, 1113 Sofia, Bulgaria²
Institute of Experimental Pathology and Parasitology, Bulgarian Academy of Sciences, 23 Academician G. Bonchev, 1113 Sofia, Bulgaria³
Anorganische Biochemie, Physiologisch-chemisches Institut der Universität, Tübingen, Hoppe-Seyler-Straße 4, D-72076, Tübingen, Germany⁴
Abteilung für Physikalische Biochemie des Physiologisch-chemischen Instituts der Universität, Tübingen, Hoppe-Seyler-Straße 4, D-72076, Tübingen, Germany⁵

Author for correspondence: Wolfgang Voelter. Tel: +49 707 12973041. Fax: +49 707 1293361. e-mail: wolfgang.voelter{at}uni-tuebingen.de

The fungal strain Humicola lutea 103 produces a naturally glycosylated Cu/Zn SOD. To improve its yield, the effect of an increased concentration of dissolved oxygen (DO) on growth and enzyme biosynthesis by the producer, cultivated in a 3 l bioreactor, was examined. Exposure to a 20% DO level caused a 1·7-fold increase of SOD activity compared to the DO-uncontrolled culture. Maximum enzyme productivity of SOD was approximately 300x10³ U (kg wet biomass)^-1. The novel enzyme was purified to electrophoretic homogeneity. The presence of Cu and Zn were confirmed by atomic absorption spectrometry. The molecular mass of H. lutea Cu/Zn SOD was calculated to be 31870 Da for the whole molecule and 15936 Da for the structural subunits. The N-terminal sequence revealed a high degree of structural homology with Cu/Zn SOD from other prokaryotic and eukaryotic sources. H. lutea Cu/Zn SOD was used in an in vivo model for the demonstration of its protective effect against myeloid Graffi tumour in hamsters. Comparative studies revealed that the enzyme (i) elongated the latent time for tumour appearance, (ii) inhibited tumour growth in the early stage of tumour progression (73–75% at day 10) and (iii) increased the mean survival time of Graffi-tumour-bearing hamsters. Moreover, the fungal Cu/Zn SOD exhibited a strong protective effect on experimental influenza virus infection in mice. The survival rate increased markedly, the time of survival rose by 5·2 d and the protective index reached 86%. The H. lutea SOD protected mice from mortality more efficiently compared to the selective antiviral drug ribavirin and to commercial bovine SOD. In conclusion, our results suggest that appropriate use of the novel fungal SOD, applied as such or in combination with selective inhibitors, could outline a promising strategy for the treatment of myeloid Graffi tumour and influenza virus infection.

Keywords: protein sequencing, myeloid Graffi tumour, influenza infection, protective effect

Abbreviations: DO, dissolved oxygen; MST, mean survival time; SOD, superoxide dismutase; TBH, tumour-bearing hamsters

This article has been cited by other articles:

				F.-x. Guo, S.-j. E, S.-a. Liu, J. Chen, and D.-c. Li Purification and characterization of a thermostable MnSOD from the thermophilic fungus Chaetomium thermophilum Mycologia, May 1, 2008; 100(3): 375 - 380. [Abstract] [Full Text] [PDF]