Ghrelin receptor agonist GHRP-2 prevents arthritis-induced increase in E3 ubiquitin-ligating enzymes MuRF1 and MAFbx gene expression in skeletal muscle.
Granado. Miriam M; Priego. Teresa T; Martín. Ana I AI; Villanúa. Maria Angeles MA; López-Calderón. Asunción A
Key Findings
- Arthritis in rats raises muscle‑specific ubiquitin ligases MuRF1 and MAFbx and TNF‑alpha mRNA, indicating increased protein breakdown.
- Eight days of GHRP‑2 treatment prevents the arthritis‑induced rise in MuRF1, MAFbx, and TNF‑alpha gene expression in skeletal muscle.
- GHRP‑2 boosts serum IGF‑I and liver IGF‑I mRNA, while lowering muscle IGFBP‑5 mRNA, supporting an anabolic environment.
Practical Outcomes
- For biohackers, GHRP‑2 may offer a way to protect muscle mass during periods of chronic inflammation or catabolic stress, but the evidence is limited to rodent models. No human dosing or safety data are provided, so any real‑world use would be experimental and should be approached with caution.
Summary
In rats with arthritis, the muscle‑wasting signals MuRF1, MAFbx and inflammatory TNF‑alpha go up, but giving the ghrelin‑like peptide GHRP‑2 for a week stops that rise and lifts overall IGF‑1 levels. This suggests GHRP‑2 can blunt muscle breakdown during chronic inflammation, though the work is in animals, not people.
Abstract
Chronic arthritis is a catabolic state associated with an inhibition of the IGF system and a decrease in body weight. Cachexia and muscular wasting is secondary to protein degradation by the ubiquitin-proteasome pathway. The aim of this work was to analyze the effect of adjuvant-induced arthritis on the muscle-specific ubiquitin ligases muscle ring finger 1 (MuRF1) and muscle atrophy F-box (MAFbx) as well as on IGF-I and IGF-binding protein-5 (IGFBP-5) gene expression in the skeletal muscle. We also studied whether the synthetic ghrelin receptor agonist, growth hormone releasing peptide-2 (GHRP-2), was able to prevent arthritis-induced changes in the skeletal muscle. Arthritis induced an increase in MuRF1, MAFbx (P < 0.01), and tumor necrosis factor (TNF)-alpha mRNA (P < 0.05) in the skeletal muscle. Arthritis decreased the serum IGF-I and its gene expression in the liver (P < 0.01), whereas it increased IGF-I and IGFBP-5 gene expression in the skeletal muscle (P < 0.01). Administration of GHRP-2 for 8 days prevented the arthritis-induced increase in muscular MuRF1, MAFbx, and TNF-alpha gene expression. GHRP-2 treatment increased the serum concentrations of IGF-I and the IGF-I mRNA in the liver and in the cardiac muscle and decreased muscular IGFBP-5 mRNA both in control and in arthritic rats (P < 0.05). GHRP-2 treatment increased muscular IGF-I mRNA in control rats (P < 0.01), but it did not modify the muscular IGF-I gene expression in arthritic rats. These data indicate that arthritis induces an increase in the activity of the ubiquitin-proteasome proteolytic pathway that is prevented by GHRP-2 administration. The parallel changes in muscular IGFBP-5 and TNF-alpha gene expression with the ubiquitin ligases suggest that they can participate in skeletal muscle alterations during chronic arthritis.
Study Information
pubmed
2005
2005-07-19T00:00:00.000Z
10.1152/ajpendo.00109.2005