What if the key to treating certain muscle diseases lies at the heart of our biological clock? This is what scientists from Inserm suggest. They have in fact discovered the decisive role for good muscle contraction of Rev-erb-α, a protein involved in the functioning of our biological clock. What is the link between the biological clock and muscle activity, which health on the net explains to you?
How does muscle contraction work?
In a healthy individual, the contraction of muscle fibers requires the release of calcium ions in the muscle cells. These calcium ions are stored within a specific compartment of the muscle cell called the “sarcoplasmic reticulum”. When a nerve signal is triggered, the sarcoplasmic reticulum releases calcium ions into the cytoplasm of muscle cells, which then triggers muscle contraction. These calcium ions will then be recaptured by a transporter called SERCA. Located on the membrane of the sarcoplasmic reticulum, this transporter has the role of reconstituting the stock.
Muscle contraction may however prove to be less effective, or even blocked, in the event of a malfunction of this mechanism. Proof of this is the various existing muscle diseases such as Duchenne muscular dystrophy. Inserm researchers, therefore, wanted to study the mechanisms involved more closely.
To know! Duchenne muscular dystrophy is one of the best-known genetic myopathies. It is linked to a mutation in the dystrophin gene (structural protein) which leads to the progressive deterioration and destruction of muscle fibers.
Biological clock: what influences muscle activity?
This is how they were able to identify an actor capable of modulating the activity of the transporter SERCA. Present in the cell nucleus, it is a Rev-erb‑α nuclear receptor. Under the control of the biological clock, the Rev-erb-α protein regulates certain physiological functions of the organism during the day. This protein is already well-known to Inserm scientists! And for good reason, they have already identified its role in the immune function of macrophages, in the metabolism of lipids as well as in the regulation of blood sugar.
To know! The Rev-erb-α protein acts as a transcription factor at the molecular level. It is responsible for regulating the first step in DNA reading, allowing DNA to be transformed into RNA. The Rev-erb-α protein has the ability to bind to certain genes and silence them at specific times of the day.
During their investigations, the scientists were able to observe the following phenomenon:
- When the expression of the gene encoding the Rev-erb-α receptor was stimulated, the mice were physically very active.
- When the expression of the gene coding for the Rev-erb-α receptor was repressed, the mice ran for less time and less quickly.
They, therefore, wanted to know the influence of the Rev-erb-α protein on muscle function, in normal or pathological conditions. They thus observed that Rev-erb‑α suppressed the expression of the gene encoding neuregulin, a small protein itself responsible for inhibiting the activity of the transporter SERCA.
In parallel, by using a molecule capable of stimulating the Rev-erb-α protein, the scientists were able to observe:
- An increase in the activity of the transporter SERCA.
- An increase in the concentration of calcium in the sarcoplasmic reticulum.
- Improved muscle contractility in healthy or diseased mice (modeling Duchenne muscular dystrophy).
- Improved contractility of muscle cells from patients with Duchenne muscular dystrophy.