Abstract
Gyroxin is a glycoprotein isolated from rattlesnake venom, with known thrombin-like serine protease properties and behavioral action in the CNS. The mechanism of the latter has eluded experimenters for three decades. In this paper about the in vitro chick retina we demonstrate an excitotoxic CNS action of Gyroxin by observing retinal Intrinsic Optical Signals (IOS). These show sudden dynamic changes in the intact tissue due to gyroxin action. The very fast kinetics of this response precludes deep tissue penetration by the protein, a mechanism of tissue response described here for the first time. At nanomolar concentrations, Gyroxin alters profoundly the optical profiles of retinal spreading depression waves (RSDs), suggesting modulation of ionic transport and metabolism. This effect is reversible in contrast with the acute cell lysis induced with gyroxin pulses at higher concentration. Because there may be more than one target of Gyroxine at the retinal inner limiting membrane, additional biochemical assays were performed to study a possible Na/K-ATPase blockade and PAR receptor activation. We conclude that the Gyroxin interaction with basement membranes of CNS and endothelium triggers conformational phase transitions at basement membranes, with multiple functional consequences.
Keywords: Retinal spreading depression, IOS, excitotoxicity, gyroxin, PAR receptors, neuronal-glial interactions, glycoprotein, (IOS), (RSDs)
Current Medicinal Chemistry
Title: Gyroxin and Its Biological Activity: Effects on CNS Basement Membranes and Endothelium and Protease-Activated Receptors
Volume: 19 Issue: 2
Author(s): J. A.A. da Silva, P. Spencer, M. A. Camillo and V. M.F. de Lima
Affiliation:
Keywords: Retinal spreading depression, IOS, excitotoxicity, gyroxin, PAR receptors, neuronal-glial interactions, glycoprotein, (IOS), (RSDs)
Abstract: Gyroxin is a glycoprotein isolated from rattlesnake venom, with known thrombin-like serine protease properties and behavioral action in the CNS. The mechanism of the latter has eluded experimenters for three decades. In this paper about the in vitro chick retina we demonstrate an excitotoxic CNS action of Gyroxin by observing retinal Intrinsic Optical Signals (IOS). These show sudden dynamic changes in the intact tissue due to gyroxin action. The very fast kinetics of this response precludes deep tissue penetration by the protein, a mechanism of tissue response described here for the first time. At nanomolar concentrations, Gyroxin alters profoundly the optical profiles of retinal spreading depression waves (RSDs), suggesting modulation of ionic transport and metabolism. This effect is reversible in contrast with the acute cell lysis induced with gyroxin pulses at higher concentration. Because there may be more than one target of Gyroxine at the retinal inner limiting membrane, additional biochemical assays were performed to study a possible Na/K-ATPase blockade and PAR receptor activation. We conclude that the Gyroxin interaction with basement membranes of CNS and endothelium triggers conformational phase transitions at basement membranes, with multiple functional consequences.
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Cite this article as:
A.A. da Silva J., Spencer P., A. Camillo M. and M.F. de Lima V., Gyroxin and Its Biological Activity: Effects on CNS Basement Membranes and Endothelium and Protease-Activated Receptors, Current Medicinal Chemistry 2012; 19 (2) . https://dx.doi.org/10.2174/092986712803414123
DOI https://dx.doi.org/10.2174/092986712803414123 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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