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Effect of peptide Semax and its C-terminal fragment PGP on Vegfa gene expression during incomplete global cerebral ischemia in rats

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Abstract

Vascular endothelial growth factor (VEGF-A) is hypoxia-inducible signal glycoprotein. VEGF-A induces vascular endothelial cell proliferation, which leads to the reconstitution of the vascular network in brain regions damaged by ischemia. However, this protein is also involved in the processes of inflammation and edema in early stages of ischemia. The synthetic peptide Semax has neuroprotective and anti-inflammatory properties and is actively used in the treatment of cerebral ischemia. We have previously shown that Semax reduces vascular injury and activates the mRNA synthesis of neurotrophins and their receptors during global cerebral ischemia in rats. In this work, we studied the effect of Semax and its C-terminal Pro-Gly-Pro tripeptide on Vegfa mRNA expression in different regions of the rat brain after 0.5, 1, 2, 4, 8, 12 and 24 h, which is the irreversible occlusion of the common carotid arteries. It was shown that ischemia increases the levels of Vegfa mRNA in rat brains (4 h after occlusion in cerebellum, cerebral cortex, and hippocampus; 8 h after occlusion in the cortex and hippocampus; and 24 h after occlusion in the cortex). Treatment with Semax reduces the levels of Vegfa mRNA in the frontal cortex (4, 8 and 12 h after occlusion) and the hippocampus (2 and 4 h after occlusion). The effect of PGP on the Vegfa gene expression was almost negligible. It was shown that Semax prevents the activating effect of hypoxia on the expression of the Vegfa gene at early stages of global cerebral ischemia. In turn, an increase in the level of Vegfa mRNA in the hippocampus 24 h after occlusion and Semax administration apparently reflects the neuroprotective properties of the drug.

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Abbreviations

PCR:

polymerase chain reaction

RT:

reverse transcription

GADPH:

glyceraldehyde-3-phosphate dehydrogenase

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Correspondence to V. V. Stavchanskii.

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Original Russian Text © V.V. Stavchanskii, T.V. Tvorogova, A.Yu. Botsina, S.A. Limborska, V.I. Skvortsova, N.F. Myasoedov, L.V. Dergunova, 2013, published in Molekulyarnaya Biologiya, 2013, Vol. 47, No. 3, pp. 461–466.

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Stavchanskii, V.V., Tvorogova, T.V., Botsina, A.Y. et al. Effect of peptide Semax and its C-terminal fragment PGP on Vegfa gene expression during incomplete global cerebral ischemia in rats. Mol Biol 47, 406–410 (2013). https://doi.org/10.1134/S0026893313030151

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  • DOI: https://doi.org/10.1134/S0026893313030151

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