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

Mazuryk, Jarosław; Puchalska, Izabela; Koziński, Kamil; Ślusarz, Magdalena J.; Ruczyński, Jarosław; Rekowski, Piotr; Rogujski, Piotr; Płatek, Rafał; Wiśniewska, Marta Barbara; Piotrowski, Arkadiusz; Janus, Łukasz; Skowron, Piotr M.; Pikuła, Michał; Sachadyn, Paweł; Rodziewicz-Motowidło, Sylwia; Czupryn, Artur; Mucha, Piotr

doi:10.3390/ijms22116086

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

^1,2,*

^3,4

⁵

^1,6

^1,7

Marta Barbara Wiśniewska

⁵

⁸

⁹,

¹⁰

⁷

Sylwia Rodziewicz-Motowidło

Artur Czupryn

and

Piotr Mucha

^3,*

Laboratory of Neurobiology, Nencki Institute of Experimental Biology PAS, 02-093 Warsaw, Poland

Department of Electrode Processes, Institute of Physical Chemistry, Polish Academy of Sciences, Kasprzaka 44/52, 01-224 Warsaw, Poland

Faculty of Chemistry, University of Gdańsk, Wita Stwosza 63, 80-308 Gdańsk, Poland

⁴

Institute of Biotechnology and Molecular Medicine, 80-172 Gdańsk, Poland

⁵

Laboratory of Molecular Neurobiology, Centre of New Technologies, University of Warsaw, 02-097 Warsaw, Poland

⁶

NeuroRepair Department, Mossakowski Medical Research Institute PAS, 02-106 Warsaw, Poland

⁷

Laboratory for Regenerative Biotechnology, Gdańsk University of Technology, 80-233 Gdańsk, Poland

⁸

Department of Biology and Pharmaceutical Botany, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland

⁹

MedVentures Company, 60-141 Poznań, Poland

¹⁰

Laboratory of Tissue Engineering and Regenerative Medicine, Department of Embryology, Medical University of Gdańsk, 80-210 Gdańsk, Poland

Authors to whom correspondence should be addressed.

Academic Editor: Cesar Borlongan

Int. J. Mol. Sci. 2021, 22(11), 6086; https://doi.org/10.3390/ijms22116086

Received: 30 April 2021 / Revised: 23 May 2021 / Accepted: 30 May 2021 / Published: 4 June 2021

(This article belongs to the Special Issue Stroke: Merging Neuroprotection and Neuroregeneration towards Therapeutics)

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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. View Full-Text

Keywords: arginine-rich peptides; cell-penetrating peptides; excitotoxicity; ischemic stroke; neural viability; neuroprotection; neurotoxicity; peptide conformation; PTD4; Tat(49–57)-NH₂

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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. Int. J. Mol. Sci. 2021, 22, 6086. https://doi.org/10.3390/ijms22116086

AMA Style

Mazuryk J, Puchalska I, Koziński K, Ślusarz MJ, Ruczyński J, Rekowski P, Rogujski P, Płatek R, Wiśniewska MB, Piotrowski A, Janus Ł, Skowron PM, 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. 2021; 22(11):6086. https://doi.org/10.3390/ijms22116086

Chicago/Turabian Style

Mazuryk, Jarosław, Izabela Puchalska, Kamil Koziński, Magdalena J. Ślusarz, Jarosław Ruczyński, Piotr Rekowski, Piotr Rogujski, Rafał Płatek, Marta Barbara Wiśniewska, Arkadiusz Piotrowski, Łukasz Janus, Piotr M. Skowron, Michał Pikuła, Paweł Sachadyn, Sylwia Rodziewicz-Motowidło, Artur Czupryn, and Piotr Mucha. 2021. "PTD4 Peptide Increases Neural Viability in an In Vitro Model of Acute Ischemic Stroke" International Journal of Molecular Sciences 22, no. 11: 6086. https://doi.org/10.3390/ijms22116086

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

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