NDP-α-MSH attenuates heart and liver responses to myocardial reperfusion via the vagus nerve and JAK/ERK/STAT signaling.
Ottani. Alessandra A; Giuliani. Daniela D; Neri. Laura L; Calevro. Anita A; Canalini. Fabrizio F; Vandini. Eleonora E; Cainazzo. Maria Michela MM; Ruberto. Ippazio Antonio IA; Barbieri. Alberto A; Rossi. Rosario R; Guarini. Salvatore S
Key Findings
- IV NDP‑α‑MSH during coronary occlusion reduced heart infarct size and arrhythmias in rats
- The peptide also lowered inflammatory signals (TNF‑α, pJNK) and boosted protective proteins (HO‑1, Bcl‑XL) in heart and liver
- Cutting the vagus nerve blocked all the protective effects, showing the vagus nerve is essential for the peptide’s action
Practical Outcomes
- While the results hint that melanotan‑I could have heart‑protective properties, the study’s conditions (IV delivery during an acute heart attack in rats) aren’t practical for self‑experimentation. Biohackers should view this as early‑stage science that may guide future drug development, not a protocol to improve personal cardiovascular health today.
Summary
In a rat study, giving the peptide NDP‑α‑MSH (melanotan‑I) through an IV line right when a heart attack was induced helped protect the heart and liver from damage, but only if the vagus nerve was intact. The protection involved turning on certain cell‑signaling pathways (JAK, ERK, STAT) and reducing inflammation markers. This effect was seen only in a controlled lab setting, not in everyday use.
Abstract
Melanocortin peptides afford cardioprotection during myocardial ischemia/reperfusion via janus kinases (JAK), extracellular signal-regulated kinases (ERK) and signal transducers/activators of transcription (STAT) pathways. Here we investigated whether melanocortin-induced modulation of the JAK/ERK/STAT signaling occurs via the cholinergic anti-inflammatory pathway, focusing our study on cardiac and hepatic responses to prolonged myocardial ischemia/reperfusion. Ischemia was produced in rats by ligature of the left anterior descending coronary artery for 30min; effects of ischemia/reperfusion were evaluated using Western blot of heart and liver proteins. Intravenous treatment, during coronary artery occlusion, with the melanocortin analog (Nle(4), D-Phe(7))α-melanocyte-stimulating hormone (NDP-α-MSH) induced a left ventricle up-regulation of the cardioprotective transcription factors pJAK2, pERK1/2 and pTyr-STAT3 (JAK-dependent), and a reduction in the levels of the inflammatory mediators tumor necrosis factor-α (TNF-α) and pJNK (a transcription factor also involved in apoptosis), as assessed at the end of the 2-h reperfusion period. Further, these beneficial effects of NDP-α-MSH were associated with heart over-expression of the pro-survival proteins heme oxygenase-1 (HO-1) and Bcl-XL, and decrease of ventricular arrhythmias and infarct size. In the liver NDP-α-MSH induced a decrease in the pJAK2 and pTyr-STAT3 levels, and strongly reduced pERK1/2 expression. In the liver of ischemic rats NDP-α-MSH also blunted pJNK activity and TNF-α expression, and up-regulated Bcl-XL. Bilateral cervical vagotomy prevented all effects of NDP-α-MSH, both in the heart and liver. These results indicate that melanocortins inhibit heart and liver damage triggered by prolonged myocardial ischemia/reperfusion likely, as main mechanism, via the vagus nerve-mediated modulation of the JAK/STAT/ERK signaling pathways.
Study Information
pubmed
2015
2015-10-22T00:00:00.000Z
10.1016/j.ejphar.2015.10.022
20
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