Mots-C
Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1, Mitochondrial-derived peptide MOTS-c
The intraperitoneal administration of MOTS-c produces antinociceptive and anti-inflammatory effects through the activation of AMPK pathway in the mouse formalin test.
Yin. Xinqiang X; Jing. Yuanyuan Y; Chen. Quan Q; Abbas. Abdul Baset AB; Hu. Jialiang J; Xu. Hanmei H
Key Findings
- MOTS‑c reduced pain‑related licking behavior in the mouse formalin test in a dose‑dependent way
- The pain‑relief effect was blocked by an AMPK antagonist, indicating AMPK activation is required
- MOTS‑c lowered pro‑inflammatory cytokines, raised anti‑inflammatory cytokines, and suppressed MAP‑kinase and c‑fos signaling in the spinal cord
Practical Outcomes
- MOTS‑c shows promise as a pain‑and‑inflammation‑reducing agent, but the study is limited to mice and uses intraperitoneal injection, which isn’t practical for humans. More research is needed to determine safe oral or injectable doses for people before it can be recommended as a supplement for pain or metabolic health.
Summary
In mice, giving MOTS‑c by injection lowered pain and inflammation, likely by turning on the AMPK pathway and shutting down some stress‑related signals in the spinal cord. The effect disappeared when an AMPK blocker was used, showing the pathway is important.
Abstract
The activation of the AMP activated protein kinase (AMPK) exerts antinociceptive effects in acute and neuropathic pain models. Mitochondrial open-reading-frame of the twelve S rRNA-c (MOTS-c), a mitochondrial-derived peptide, regulates many biological activities via activating AMPK. However, the role of MOTS-c in the formalin-induced inflammatory nociception remains unclear. In this study, we investigated the role of MOTS-c in the formalin-induced inflammatory nociception. The antinociceptive effect of MOTS-c was assessed by recording the time spent licking paw. The anti-inflammatory effect of MOTS-c was evaluated by detecting the inflammatory cytokine level changes in the mouse serum. Western blot was used to detect the changes of protein phosphorylation levels in the mouse spinal cord. Changes of c-fos expression in the spinal cord were assessed by immunohistochemistry. Our results showed that the intraperitoneal administration of MOTS-c reduced the time spent on licking in phase 2 in a dose-dependent manner in the formalin test. The antinociceptive effects of MOTS-c (50 mg/kg, i.p.) were attenuated by the AMPK antagonist compound C (10 mg/kg, i.p.). MOTS-c (50 mg/kg, i.p.) significantly reduced pro-inflammatory cytokine levels and elevated the level of anti-inflammatory cytokine in mouse serum. In addition, MOTS-c treatment significantly increased AMPKα phosphorylation level and suppressed formalin-induced extracellular signal-regulated kinase (ERK), c-Jun amino-terminal kinases (JNK), and P38 activation and c-fos expression in the mouse spinal cord. These results suggest that systemic administration of MOTS-c exerts antinociceptive and anti-inflammatory effects, at least partially, through activating AMPK pathway and inhibiting MAP kinases-c-fos signaling pathway in the mouse formalin test.
Study Information
pubmed
2020
2020-01-08T00:00:00.000Z
10.1016/j.ejphar.2020.172909
39
34