PTD4 Peptide Increases Neural Viability in an In Vitro Model of Acute Ischemic Stroke - Publication - Bridge of Knowledge

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PTD4 Peptide Increases Neural Viability in an In Vitro Model of Acute Ischemic Stroke

Abstract

Ischemic stroke is a disturbance in cerebral blood flow caused by brain tissue ischemia and hypoxia. We optimized a multifactorial in vitro model of acute ischemic stroke using rat primary neural cultures. This model was exploited to investigate the pro-viable activity of cell-penetrating peptides: arginine-rich Tat(49–57)-NH2 (R49KKRRQRRR57-amide) and its less basic analogue, PTD4 (Y47ARAAARQARA57-amide). Our model included glucose deprivation, oxidative stress, lactic acidosis, and excitotoxicity. Neurotoxicity of these peptides was excluded below a concentration of 50 μm, and PTD4-induced pro-survival was more pronounced. Circular dichroism spectroscopy and molecular dynamics (MD) calculations proved potential contribution of the peptide conformational properties to neuroprotection: in MD, Tat(49–57)-NH2 adopted a random coil and polyproline type II helical structure, whereas PTD4 adopted a helical structure. In an aqueous environment, the peptides mostly adopted a random coil conformation (PTD4) or a polyproline type II helical (Tat(49–57)-NH2) structure. In 30% TFE, PTD4 showed a tendency to adopt a helical structure. Overall, the pro-viable activity of PTD4 was not correlated with the arginine content but rather with the peptide’s ability to adopt a helical structure in the membrane-mimicking environment, which enhances its cell membrane permeability. PTD4 may act as a leader sequence in novel drugs for the treatment of acute ischemic stroke.

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Category:
Articles
Type:
artykuły w czasopismach
Published in:
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES no. 22,
ISSN: 1661-6596
Language:
English
Publication year:
2021
Bibliographic description:
Mazuryk J., Puchalska I., Koziński K., Ślusarz M. J., Ruczyński J., Rekowski P., Rogujski P., Płatek R., Wiśniewska M. B., Piotrowski A., Janus Ł., Skowron P. M., Pikuła M., Sachadyn P., Rodziewicz-Motowidło S., Czupryn A., Mucha P.: PTD4 Peptide Increases Neural Viability in an In Vitro Model of Acute Ischemic Stroke// INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES -Vol. 22,iss. 11 (2021), s.6086-
DOI:
Digital Object Identifier (open in new tab) 10.3390/ijms22116086
Verified by:
Gdańsk University of Technology

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