ACTH(6-9)PGP Peptide Protects SH-SY5Y Cells from the H2O2, tert-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Prolif-eration Stimulation and Antioxidant-related Genes Induction

Akimov, M. G.; Ev, Fomina-Ageeva; Pv, Dudina; La, Andreeva; Nf, Myasoyedov; Vv, Bezuglov

doi:10.20944/preprints202103.0139.v1

2021

DOI: 10.20944/preprints202103.0139.v1

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ACTH(6-9)PGP Peptide Protects SH-SY5Y Cells from the H2O2, tert-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Prolif-eration Stimulation and Antioxidant-related Genes Induction

M. G. Akimov¹,

Fomina-Ageeva Ev²,

Dudina Pv³

et al.

Abstract: Stabilized melanocortin analog peptide ACTH(6-9)PGP (FRWGPGP) possess a wide range of neuroprotective activities. However, its mechanism of action remains poorly understood. In this paper, we studied the pro-proliferative and cytoprotective activity of the adrenocorticotropic hormone fragment 6-9 (FRWG) linked with the peptide Prolyl-Glycyl-Proline on the SH-SY5Y cells in the model of oxidative stress-related toxicity. The peptide dose-dependently protected cells from H2O2, tert-butyl hydroperoxide, and KCN. T… Show more

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Cited by 7 publications

References 31 publications

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Effects of His-Phe-Arg-Trp-Pro-Gly-Pro peptide on free-radical oxidation processes in conditions of chronic restraint stress

Vorvul

Bobyntsev

Медведева

et al. 2021

BRSMU

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Studying the effects of regulatory peptides on the stress-induced shifts in the bodily processes is of great fundamental and applied significance. Currently, a wide range of peptide neurotropic drugs, affecting the stress response development, are used in medicine, and new promising molecules are being studied. The study was aimed to assess the effects of the adrenocorticotropic hormone (ACTH) synthetic analog, ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5, 50 and 500 μg/kg, on the free-radical oxidation processes in Wistar rats, subjected to chronic restraint stress (CRS) during two weeks. Serum levels of 8-oxo-2'-deoxyguanosine (8-OHdG) and superoxide dismutase 3 (SOD3) were assessed by enzyme immunoassay, and the levels of thiobarbituric acid reactive substances (TBARS) were assessed by fluorimetric method. CRS lead to the significant increase in the 8-OHdG levels by 18.4% (p = 0.01) and the decrease in the SOD3 levels by 14.3% (p = 0.01), however, it had no effect on the levels of TBARS. ACTH(6-9)-Pro-Gly-Pro, administered at a dose of 5 and 50 μg/kg, significantly decreased the levels of 8-OHdG by 19.8% (p = 0.03) and 30% (p = 0.001), respectively. Thus, it was found that CRS resulted in oxidative stress in animals. ACTH(6-9)-Pro-Gly-Pro administration at a dose of 5 and 50 μg/kg inhibits the stress-induced free-radical oxidation processes.

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Effects of His-Phe-Arg-Trp-Pro-Gly-Pro peptide on free-radical oxidation processes in conditions of chronic restraint stress

Vorvul

Bobyntsev

Медведева

et al. 2021

BRSMU

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ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke

Filippenkov,

Shpetko,

Stavchansky

et al. 2024

Biomedicines

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Background: Ischemic stroke results from a disruption of cerebral blood flow. Adrenocorticotropic hormone (ACTH) serves as the basis for the creation of synthetic peptides as neuroprotective agents for stroke therapy. Previously, using RNA-Seq we first revealed differential expressed genes (DEGs) associated with ACTH(4–7)PGP (Semax) and ACTH(6–9)PGP peptides under cerebral ischemia conditions. Analysis was carried out at 4.5 h after transient middle cerebral artery occlusion (tMCAO) model in the ipsilateral frontal cortex of a rat brain. Methods: Here, we analyzed the penumbra-associated frontal cortex of rats and actions under the same peptides at 24 h after tMCAO using RNA-Seq. Results: 3774 DEGs (fold change > 1.5 and Padj < 0.05) were identified under ischemia conditions, whereas 1539 and 2066 DEGs were revealed under Semax and ACTH(6–9)PGP peptides at 24 h after tMCAO. Furthermore, both peptides significantly reduced expression distortions caused by ischemia for 1171 genes associated with immune and neurosignaling pathways. Concomitantly, there were 32 DEGs under ACTH(6–9)PGP versus Semax administration at 24 h after tMCAO. Besides, neurogenesis-, angiogenesis-, protein kinase- and growth factor-related DEGs were revealed under peptides action. Previously, we observed the neuroprotective effect of peptides at the histological level in rat brains at 24 h after tMCAO. Thus, here we demonstrate the transcriptome manifestation of this histological effect. Furthermore, comparison with previous data at the 4.5 h post-tMCAO time point showed that the pattern of peptide action on the transcriptome depends on the time elapsed after tMCAO. Conclusions: We revealed that the effect of ACTH(6–9)PGP was more similar to Semax than different from it a day after tMCAO. At this time point, ACTH-like peptides compensated rat brain gene expression profiles disrupted by ischemia. Thus, our results may be useful for selecting more effective structures for future anti-stroke drugs and appropriate post-stroke time points for their testing.

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Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia

Stavchansky,

Yuzhakov,

Sevan’kaeva

et al. 2024

CIMB

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Stroke remains the second leading cause of death worldwide. The development of new therapeutic agents focused on restoring vascular function and neuroprotection of viable tissues is required. In this study the neuroprotective activity of melanocortin-like ACTH(4–7)PGP and ACTH(6–9)PGP peptides was investigated in rat brain at 24 h after transient middle cerebral artery occlusion (tMCAO). The severity of ischemic damage, changes in the proliferative activity of neuroglial cells and vascularization of rat brain tissue were analyzed. The administration of peptides resulted in a significant increase in the volume density of neurons in the perifocal zone of infarction compared to rats subjected to ischemia and receiving saline. Immunohistochemical analysis of the proliferative activity of neuroglia cells using PCNA antibodies showed a significant increase in the number of proliferating cells in the penumbra and in the intact cerebral cortex of rats receiving peptide treatment. The effect of peptides on vascularization was examined using CD31 antibodies under tMCAO conditions, revealing a significant increase in the volume density of vessels and their sizes in the penumbra after administration of ACTH(4–7)PGP and ACTH(6–9)PGP. These findings confirm the neuroprotective effect of peptides due to the activation of neuroglia proliferation and the enhancement of collateral blood flow.

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ACTH(6-9)PGP Peptide Protects SH-SY5Y Cells from the H2O2, tert-Butyl Hydroperoxide, and Cyanide Cytotoxicity via Prolif-eration Stimulation and Antioxidant-related Genes Induction

Cited by 7 publications

References 31 publications

Effects of His-Phe-Arg-Trp-Pro-Gly-Pro peptide on free-radical oxidation processes in conditions of chronic restraint stress

Effects of His-Phe-Arg-Trp-Pro-Gly-Pro peptide on free-radical oxidation processes in conditions of chronic restraint stress

ACTH-like Peptides Compensate Rat Brain Gene Expression Profile Disrupted by Ischemia a Day After Experimental Stroke

Melanocortin Derivatives Induced Vascularization and Neuroglial Proliferation in the Rat Brain under Conditions of Cerebral Ischemia

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