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Enhanced HGF with increased receptor affinity and nitration-dysfunction resistance through interaction with lipoic
Kahona Zushi1, Miyumi Seki1, Ryota Mizuochi1
1Department of Animal and Marine Bioresource Sciences, Graduate School of Agriculture, Kyushu University, West Zone 5, Motooka 744, Nishi-ku, Fukuoka, 819-0395, Japan.
Scientific Reports
|July 24, 2026
Summary
Lipoic acid trisulfide (LASSS) enhances myogenic stem cell activator HGF binding to its receptor and prevents nitration damage. This discovery offers potential strategies against age-related muscle atrophy and frailty.
Area of Science:
- Biochemistry
- Cell Biology
- Aging Research
Background:
- Hepatocyte growth factor (HGF), a myogenic stem cell activator, loses receptor binding affinity due to tyrosine nitration during aging.
- Peroxynitrite generation during aging causes HGF nitration, primarily affecting fast-twitch fibers and impairing c-met signaling.
Purpose of the Study:
- To investigate the effect of lipoic acid trisulfide (LASSS) on HGF's receptor-binding affinity and nitration resistance.
- To explore LASSS as a potential therapeutic strategy for age-related muscle decline.
Main Methods:
- HGF was treated with LASSS at a 1:8000 molar ratio, followed by ultra-filtration.
- c-met binding affinity was measured using assays.
- Nitration resistance at specific tyrosine residues (Y198, Y250) was assessed.
- A tail-suspension mouse model was used to evaluate LASSS efficacy in preventing disuse-induced HGF nitration.
Main Results:
- LASSS treatment increased HGF's c-met binding affinity by over two-fold.
- LASSS conferred significant resistance to HGF nitration, particularly at Y198.
- LASSS administration in mice prevented disuse-induced HGF nitration, unlike glutathione trisulfide (GSSSG).
Conclusions:
- LASSS enhances HGF's receptor-binding affinity and protects it from nitration-induced dysfunction.
- LASSS demonstrates potential for counteracting age-related muscle atrophy and improving regeneration.
- This interaction represents a novel mechanism for maintaining myogenic stem cell homeostasis.
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