Elucidation of the effect of brain cortex tetrapeptide Cortagen on gene expression in mouse heart by microarray
Sergey V Anisimov1, Vladimir Kh Khavinson, Vladimir N Anisimov
1Saint-Petersburg Institute of Bioregulation and Gerontology, RAMS, St.-Petersburg, Russia.
Objectives:
Aging is associated with significant alterations in gene expression in numerous organs and tissues. Anti-aging therapy with peptide bioregulators holds much promise for the correction of age-associated changes, making a screening for their molecular targets in tissues an important question of modern gerontology. The synthetic tetrapeptide Cortagen (Ala-Glu-Asp-Pro) was obtained by directed synthesis based on amino acid analysis of natural brain cortex peptide preparation Cortexin. In humans, Cortagen demonstrated a pronounced therapeutic effect upon the structural and functional posttraumatic recovery of peripheral nerve tissue. Importantly, other effects were also observed in cardiovascular and cerebrovascular parameters.
Design:
Based on these latter observations, we hypothesized that acute course of Cortagen treatment, large-scale transcriptome analysis, and identification of transcripts with altered expression in heart would facilitate our understanding of the mechanisms responsible for this peptide biological effects. We therefore analyzed the expression of 15,247 transcripts in the heart of female 6-months CBA mice receiving injections of Cortagen for 5 consecutive days was studied by cDNA microarrays.
Results:
Comparative analysis of cDNA microarray hybridisation with heart samples from control and experimental group revealed 234 clones (1,53% of the total number of clones) with significant changes of expression that matched 110 known genes belonging to various functional categories. Maximum up- and down-regulation was +5.42 and -2.86, respectively.
Conclusion:
Intercomparison of changes in cardiac expression profile induced by synthetic peptides (Cortagen, Vilon, Epitalon) and pineal peptide hormone melatonin revealed both common and specific effects of Cortagen upon gene expression in heart.
Insights
Synthetic peptide Cortagen impacts gene expression in the heart, offering potential for anti-aging therapies. This study identified 110 genes with altered expression, revealing Cortagen
Area of Science:
- Gerontology
- Molecular Biology
- Cardiovascular Research
Background:
- Aging significantly alters gene expression across tissues.
- Peptide bioregulators show promise for anti-aging interventions.
- Cortagen, a synthetic tetrapeptide, aids nerve tissue recovery and affects cardiovascular/cerebrovascular parameters.
Purpose of the Study:
- To investigate Cortagen's molecular targets in the heart.
- To understand the mechanisms behind Cortagen's biological effects.
- To analyze gene expression changes in the heart following Cortagen treatment.
Main Methods:
- Transcriptome analysis using cDNA microarrays.
- Studied 15,247 transcripts in female CBA mice hearts.
- Cortagen administered daily for 5 consecutive days.
Main Results:
- Significant expression changes in 234 clones (1.53% of total).
- Identified 110 known genes with altered expression.
- Observed maximum up-regulation of +5.42 and down-regulation of -2.86.
Conclusions:
- Cortagen influences cardiac gene expression profiles.
- Revealed common and specific gene expression effects compared to other peptides and melatonin.
- Highlights Cortagen's potential role in cardiovascular health and aging.
