LASSS enhanced HGF binding to a receptor important for muscle repair

• LASSS enhanced HGF binding to the c-met receptor more than twofold in a laboratory experiment
• HGF is involved in activating satellite cells, which help repair muscle tissue
• The tests describe a molecular effect, not a proven treatment for age-related loss of muscle function

Age weakens the muscle repair system

Skeletal muscles allow people to move, lift objects, and maintain posture, but with age, their strength and ability to recover can decline. Over time, fat deposits and scar tissue can accumulate in the tissues, while the number of specialized fibers needed for fast, powerful movements may decrease. These changes affect more than just physical performance: everyday activities become harder, and mobility and independence gradually diminish.

Researchers in Japan studied one mechanism that may be linked to declining muscle regeneration. The team, led by Professor Ryuichi Tatsumi of the Faculty of Agriculture at Kyushu University, focused on the HGF protein and its interaction with a cell receptor. The study was published in Scientific Reports. The authors view their findings as a possible basis for a new approach, but do not report a ready-made therapy or a proven way to stop age-related changes.

Skeletal muscles have their own system for repairing wear and damage. Satellite cells—specialized stem cells located next to muscle fibers—play an important role in this process. They are usually inactive, but when needed they can activate, multiply, and develop into muscle cells. In this way, they help repair damaged tissue. How effectively this process gets underway depends, among other things, on the molecular signals the cells receive.

HGF signals satellite cells

One such signal is a protein known as hepatocyte growth factor, or HGF. Despite its name, its functions are not limited to the liver: in muscles, it helps activate satellite cells. Under normal conditions, HGF is found in the supportive material around muscle fibers. When a muscle is injured, moved, or stretched, the protein can be released and then bind to the c-met receptor on the surface of cells involved in regeneration.

By binding to c-met, HGF helps bring satellite cells out of their resting state. The cells can then multiply, mature, and contribute to the repair of muscle fibers. Receptors in this system work like molecular signal reception points: when a protein interacts with a receptor, it triggers a response inside the cell. That is why it is important not only to produce HGF, but also to preserve its ability to recognize and activate c-met. Disruption of this interaction can weaken one stage of the muscles’ natural repair process.

Previous research by the group found that HGF can undergo nitration—a chemical modification in which a nitro group attaches to specific sites on the protein. This change can alter the protein’s properties and interfere with its normal function. In HGF, the researchers identified two vulnerable sites: Y198 and Y250. Both are located in a region needed for binding to c-met. If these sites are nitrated, it becomes harder for the protein to interact with the receptor.

Nitration interferes with the protein’s ability to bind to the receptor

The authors suggest that this could explain some of the age-related decline in regeneration: HGF may continue to be produced, but a chemical change to the protein after it is made can prevent it from transmitting signals to cells. In that case, the problem is not simply a shortage of the growth factor itself. Professor Tatsumiya described this possibility as a reason to look for a compound that could protect HGF from nitration or compensate for the resulting loss of function. This remains a proposed mechanism, not an established cause of all age-related changes in muscle.

To test the idea, the team studied two compounds with antioxidant properties: glutathione trisulfide, denoted GSSSG, and lipoic trisulfide, LASSS. Antioxidants can limit certain types of chemical damage caused by reactive molecules. Both substances belong to the trisulfide family, characterized by a chain of three bonded sulfur atoms. According to the study description, these molecules can participate in redox reactions.

In initial laboratory experiments, both GSSSG and LASSS reduced nitration at two vulnerable sites on HGF. However, this was not enough to fully restore the protein’s ability to bind to its receptor. The researchers therefore changed the amount of trisulfide relative to HGF. The source states that the molar ratio was changed from 1:4000 to 1:8000, and at the higher concentration, the researchers observed an effect that went beyond simply reducing chemical modification of the protein.

LASSS enhanced binding, but the clinical effect has not been tested

LASSS showed a particularly notable result: HGF treated with it bound to c-met more than twice as strongly as untreated protein. In other words, the experiment showed increased affinity for the receptor—an important step in signaling to satellite cells. LASSS also made HGF more resistant to loss of function due to nitration, particularly at position Y198. These observations relate to molecular measurements and, by themselves, do not show that the participants experienced improvements in strength or muscle recovery.

The effect on binding was specific to LASSS in the experiments described. GSSSG also reduced HGF nitration at an early stage, but did not produce a similar increase in interaction with c-met. This difference is important for interpretation: the shared antioxidant effect of the two compounds does not fully explain the result obtained with LASSS. The study points to a specific effect of this particular trisulfide on the protein–receptor interaction, but the data presented do not establish exactly how this enhancement occurs.

For now, the practical significance of the discovery is limited to the possibility of better understanding the molecular regulation of muscle recovery. The description provided presents laboratory experiments involving HGF, nitration, and the receptor, but does not report testing LASSS as a treatment in people or assessing its effect on everyday mobility. Therefore, it cannot be concluded that the compound prevents age-related muscle loss or restores strength. The next important question is whether the effect can be confirmed beyond the experiments described and whether it applies to living muscle tissue.

Source: ScienceDaily