Effects of Colostrinin™ on gene expression-transcriptomal network analysis

Szaniszlo, Peter; Germán, Péter; Hajas, György; Saenz, David N.; Woodberry, Mitchell W.; Kruzel, Marian L.; Boldogh, István

doi:10.1016/j.intimp.2008.10.022

Cited by 12 publications

(9 citation statements)

References 66 publications

(92 reference statements)

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“…These networks were ranked based on the significance score value calculated by the IPA software. A graphical representation of the molecular relationships between genes/gene products for each of the top ranked networks was generated where genes or gene products are represented as nodes, and the biological relationship between two nodes is represented as an edge (Szaniszlo et al, 2009). …”

Section: Methodsmentioning

confidence: 99%

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

Germán

Saenz

Szaniszlo

et al. 2017

Mechanisms of Ageing and Development

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Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER “wires” senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed --86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.

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Section: Methodsmentioning

confidence: 99%

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

Germán

Saenz

Szaniszlo

et al. 2017

Mechanisms of Ageing and Development

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“…Transcriptional analysis showed that Colostrinin alters the gene expression of the molecular network implicated in A precursor protein synthesis, tau phosphorylation, and increased levels of enzymes that proteolytically eliminate A . CLN-modulated gene networks represent a potential molecular mechanism leading to the reported multipotent activity of PRP/Colostrinin on cellular oxidative state, cytokine production, and cell differentiation as well as on pathological processes such as Alzheimer's disease, allergy, asthma, and other immunological diseases [147,148]. The expressions of many genes, including those for inducible nitric oxide synthase and cytokines IL-1 , IL-6, and TNF-, that affect the inflammatory process are under the control of the transcription factor NF-B.…”

Section: Potential Mechanism Of Prp/colostrinin Actionmentioning

confidence: 99%

Colostral Proline-Rich Polypeptides – Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease

Janusz¹,

Zabłocka

2010

CAR

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A proline-rich polypeptide complex (PRP), subsequently called Colostrinin(CLN), was first isolated from ovine colostrum, was shown to possess immunoregulatory properties, including effects on the maturation and differentiation of murine thymocytes and humoral and cellular immune responses, both in vivo and in vitro. PRP seems to restore balance in cellular immune functions and is not species specific. PRP is a complex of peptides of molecular masses ranging from 500 to 3000 Da. The polypeptide contains 25% proline and 40% hydrophobic amino acids. PRP shows a regulatory activity in cytokine (IFN, TNF-alpha, IL-6, IL-10) induction and possesses the ability to inhibit the overproduction of oxygen reactive species and nitric oxide. Besides its immunoregulatory activity, PRP also showed psychotropic properties, improving cognitive activity and behavior of old rats, humans, and chickens. The properties of PRP prompted the authors to propose the complex for the treatment neurodegenerative disorders. Beneficial effects of PRP/Colostrinin were shown for the first time in double-blind placebo-controlled trials and long-term open-label studies. The results were confirmed in multicenter clinical trials. A very important property of PRP/Colostrinin is the prevention of Abeta aggregation and the disruption of already existing aggregates. The same properties were expressed by one of PRP's components, a nonapeptide (NP). Moreover, PRP modulates neurite outgrowth, suppresses uncontrolled activation of cells, reduces 4-HNE-mediated cellular damage, and modulates expression in cellular redox regulation, cell proliferation, and differentiation. Its biological response modifying activity can play an important role in its use in the treatment of Alzheimer's disease.

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“…No: #1912), according to the manufacturer’s recommendation, and as we previously described (Szaniszlo et al, 2009). Briefly, the washed cell pellets were lysed in 350 µl lysis-binding solution.…”

Section: Methodsmentioning

confidence: 99%

Aerobic endurance capacity affects spatial memory and SIRT1 is a potent modulator of 8-oxoguanine repair

et al. 2013

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Regular exercise promotes brain function via a wide range of adaptive responses, including the increased expression of antioxidant and oxidative DNA damage-repairing systems. Accumulation of oxidized DNA base lesions and strand breaks is etiologically linked to for example aging processes and age-associated diseases. Here we tested whether exercise training has an impact on brain function, extent of neurogenesis, and expression of 8-oxoguanine DNA glycosylase-1 (Ogg1) and SIRT1 (silent mating type information regulation 2 homolog). To do so, we utilized strains of rats with low- and high- running capacity (LCR and HCR) and examined learning and memory, DNA synthesis, expression, and posttranslational modification of Ogg1 hippocampal cells. Our results showed that rats with higher aerobic/running capacity had better spatial memory, and expressed less Ogg1, when compared to LCR rats. Furthermore, exercise increased SIRT1 expression and decreased acetylated Ogg1 (AcOgg1) levels, a post-translational modification important for efficient repair of 8-oxoG. Our data on cell cultures revealed that nicotinamide, a SIRT1-specific inhibitor, caused the greatest increase in the acetylation of Ogg1, a finding further supported by our other observations that silencing SIRT1 also markedly increased the levels of AcOgg1. These findings imply that high-running capacity is associated with increased hippocampal function, and SIRT1 level/activity and inversely correlates with AcOgg1 levels and thereby the repair of genomic 8-oxoG.

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Effects of Colostrinin™ on gene expression-transcriptomal network analysis

Cited by 12 publications

References 66 publications

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

8-Oxoguanine DNA glycosylase1–driven DNA repair—A paradoxical role in lung aging

Colostral Proline-Rich Polypeptides – Immunoregulatory Properties and Prospects of Therapeutic Use in Alzheimers Disease

Aerobic endurance capacity affects spatial memory and SIRT1 is a potent modulator of 8-oxoguanine repair

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