Pinealon increases cell viability by suppression of free radical levels and activating proliferative processes.

The synthetic tripeptide pinealon (Glu-Asp-Arg) demonstrates dose-dependent restriction of reactive oxygen species (ROS) accumulation in cerebellar granule cells, neutrophils, and pheochromocytoma (PC12) cells, induced by oxidative stress stimulated by receptor-dependent or -independent processes. At the same time, pinealon decreases necrotic cell death measured by the propidium iodide test. The protective effect of pinealon is accompanied with a delayed time course of ERK 1/2 activation and modification of the cell cycle. Because restriction of ROS accumulation and cell mortality is saturated at lower concentrations, whereas cell cycle modulation continues at higher concentrations of pinealon, one can conclude that besides its known antioxidant activity, pinealon is able to interact directly with the cell genome.

[1]  E. Akkuratov,et al.  Receptor-mediated oxidative stress in murine cerebellar neurons is accompanied by phosphorylation of MAP (ERK 1/2) kinase. , 2013, Current aging science.

[2]  E. Bryushkova,et al.  Effect of homocysteine on properties of neutrophils activated in vivo , 2011, Biochemistry (Moscow).

[3]  A. Boldyrev,et al.  Different neuronal Na+/K+‐ATPase isoforms are involved in diverse signaling pathways , 2010, Cell biochemistry and function.

[4]  V. Anisimov,et al.  Peptide bioregulation of aging: results and prospects , 2010, Biogerontology (Dordrecht).

[5]  W. Burhans,et al.  The cell cycle is a redox cycle: linking phase-specific targets to cell fate. , 2009, Free radical biology & medicine.

[6]  L. M. Chailakhyan,et al.  Cortexin and combination of nitrite with cortexin decrease swelling and destruction of cerebellar neurons in hemorrhagic stroke , 2009, Doklady Biological Sciences.

[7]  G. Lizard,et al.  Flow cytometric investigation of neutrophil oxidative burst and apoptosis in physiological and pathological situations , 2009, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[8]  A. Sidhu,et al.  Dopamine promotes striatal neuronal apoptotic death via ERK signaling cascades , 2009, The European journal of neuroscience.

[9]  V. Khavinson,et al.  Regulatory peptides protect brain neurons from hypoxia in vivo , 2008, Doklady Biological Sciences.

[10]  Khavinson VKh,et al.  Biological activity of regulatory peptides in model experiments in vitro , 2008 .

[11]  V. Khavinson,et al.  [Biological activity of regulatory peptides in model experiments in vitro]. , 2008, Advances in gerontology = Uspekhi gerontologii.

[12]  E. Wei,et al.  Carnosine protects against NMDA-induced neurotoxicity in differentiated rat PC12 cells through carnosine-histidine-histamine pathway and H(1)/H(3) receptors. , 2007, Biochemical pharmacology.

[13]  E. Klann,et al.  Sources and targets of reactive oxygen species in synaptic plasticity and memory. , 2006, Antioxidants & redox signaling.

[14]  D. Carpenter,et al.  Glutamate receptors communicate with Na+/K+-ATPase in rat cerebellum granule cells , 2007, Journal of Molecular Neuroscience.

[15]  N. Myasoedov,et al.  Natural and hybrid ("chimeric") stable regulatory glyproline peptides. , 2005, Pathophysiology : the official journal of the International Society for Pathophysiology.

[16]  V. Khavinson,et al.  Gerontological Aspects of Genome Peptide Regulation , 2005 .

[17]  Jiang Tian,et al.  Ouabain Assembles Signaling Cascades through the Caveolar Na+/K+-ATPase* , 2004, Journal of Biological Chemistry.

[18]  M. Pallàs,et al.  Flow cytometric determination of cytoplasmic oxidants and mitochondrial membrane potential in neuronal cells. , 2002, Methods in enzymology.

[19]  A. Boldyrev Discrimination between apoptosis and necrosis of neurons under oxidative stress. , 2000, Biochemistry. Biokhimiia.

[20]  C. Gabriel,et al.  Evaluation of free radical production, mitochondrial membrane potential and cytoplasmic calcium in mammalian neurons by flow cytometry. , 1999, Brain research. Brain research protocols.