For the first time, a method for isolation and purification of the total fraction of NOX isoforms (NOX1 + NOX2) and the total fraction of O2 – producing stable associates of NOX and NADPH isoformscontaining lipoprotein (NCL associate) from the membranes of cells and intracellular formations of the spinal cord (SC) and bone marrow (BM) was developed in a rat model of fructose-induced diabetes. Characteristic changes of the optic spectra related to the level of NOX and associates were examined. Thus, an important source of O2 – radicals under conditions of oxidative stress, namely, NOX and its associates, has been identified in experiments on rats. It was found that the amounts of NOX and its associates and, respectively, the activity of these biochemical systems in animals with experimental fructose-induced type II diabetes are significantly greater than those in control rats. In turn, the respective indices in diabetic rats with additional severe impairment of the spinal cord (partial transection) are considerably higher than those in diabetic rats with no spinal cord trauma. Such findings confirm the statement that oxidative stress is a significant pathogenetic factor under conditions of both diabetes and spinal cord injury. Possible applications of the obtained experimental data in the treatment of the above pathological events are discussed.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
R. M. Simonyan, G. M. Simonyan, and M. A. Simonyan, “Method for isolation of NADPH oxidase (NOX) isoforms from biosystems. License of invention N2828,” Intellectual Ownership of the Agency of the Republic Armenia, Yerevan (2014).
N. D. Vaziri, Y. S. Lee, C. Y. Lin, et al., “NAD(P)H oxidase, superoxide dismutase, catalase, glutathione peroxidase and nitric oxide synthase expression in subacute spinal cord injury,” Brain Res., 995, No. 1, 76–83 (2004).
R. E. von Leden, G. Khayrullina, K. E. Moritz, and K. R. Byrnes, “Age exacerbates microglial activation, oxidative stress, inflammatory and NOX2 gene expression, and delays functional recovery in a middle-aged rodent model of spinal cord injury,” J. Neuroinflammation, 14, No. 1, 161 (2017).
S. Bermudez, G. Khayrullina, Y. Zhao, and K. R. Byrnes, “NADPH oxidase isoform expression is temporally regulated and may contribute to microglial/macrophage polarization after spinal cord injury,” Mol. Cell Neurosci., 77, 53–64 (2016).
S. J. Cooney, Y. Zhao, and K. R. Byrnes, “Characterization of the expression and inflammatory activity of NADPH oxidase after spinal cord injury,” Free Radic. Res., 48, No. 8, 929–939 (2014).
K. R. Byrnes, P. M. Washington, S. M. Knoblach, et al., “Delayed inflammatory mRNA and protein expression after spinal cord injury,” J. Neuroinflammation, 8, 130 (2011).
B. Zhang, W. M. Bailey, A. L. McVicar, and J. C. Gensel, “Age increases reactive oxygen species production in macrophages and potentiates oxidative damage after spinal cord injury,” Neurobiol. Aging, 47, 157–167 (2016).
V. A. Chavushyan, K. V. Simonyan, R. M. Simonyan, et al., “Effects of Stevia on synaptic plasticity and NADPH oxidase level of CNS in conditions of metabolic disorders caused by fructose,” BMC Complement. Altern. Med., 17, No. 1, 540 (2017).
X. Fu, G. Liu, A. Halim, et al., “Mesenchymal stem cell migration and tissue repair,” Cells, 8, No. 8, 784 (2019).
A. Shao, Sh. Tu, J. Lu, and J. Zhang, “Crosstalk between stem cell and spinal cord injury: pathophysiology and treatment strategies,” Stem Cell Res. Ther., 10, No. 6, 238 (2019).
M. A. Simonyan, A. V. Karapetyan, M. A. Babayan, and R. M. Simonyan, “NADPH-containing superoxideproducing lipoprotein fraction of blood serum. Isolation, purification, brief characterization and mechanism of action,” Biochemistry (Moscow), 61, No. 5, 932–938 (1996).
L Wang, M. Chopp, a. Szalad, et al., “Thymosin β4 promotes the recovery of peripheral neuropathy in type II diabetic mice,” Neurobiol. Dis.., 48, 3, 546–555 (2012).
N. Lukáčová, J. Pavol, and J. Maršala, “Phospholipid composition in spinal cord regions after ischemia/reperfusion,” Neurochem. Res., 23, No. 8, 1069–1077 (1998).
A. Diaz-Ruiz, C. Rios, I. Duarte, et al., “Lipid peroxidation inhibition in spinal cord injury: cyclosporin-A vs. methylprednisolone,” Neuroreport, 11, No. 8, 1765–1767 (2000).
A. Coyoy-Salgado, J. J. Segura-Uribe, C. Guerra-Araiza, et al., “The importance of natural antioxidants in the treatment of spinal cord injury in animal models: an overview,” Oxid. Med. Cell. Longev., 2019, 3642491 (2019).
C. Rask-Madsen and G. L. King, “Vascular complications of diabetes: mechanisms of injury and protective factors,” Cell Metab., 17, No. 1, 20–33 (2013).
Yu. A. Vladimirov and A. I. Archacov, Lipid Peroxidation in Biomembranes, Nauka, Moscow (1972).
R. M. Simonyan, K. A. Galoyan, G. M. Simonyan, et al., “Ferrihemoglobin induces the release of NADPH oxidase from brain- membrane tissue ex vivo: the suppression of this process by galarmin,” Neurochem. J., 7, No. 3, 221–225 (2013).
M. S. Sirakanyan, G. R. Oksuzyan, R. M. Simonyan, et al., “Effect of Mo+6 and cadmium ions on super-oxide-producing and meth-Hb-reducing activity of new isoform of cytochrome b558 from spleen cell membranes in vitro,” Biol. J. Armenia, Nos. 3–4, 185–189 (2006).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Simonyan, K.V., Chavushyan, V.A., Lorikyan, A.G. et al. NADPH Oxidase and Superoxide-Producing Associates in Cells of the Spinal Cord and Bone Marrow in Diabetic Rats with Spinal Cord Injury. Neurophysiology 52, 423–429 (2020). https://doi.org/10.1007/s11062-021-09900-w
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11062-021-09900-w