(889.1) ALDH2 Deficiency Enhances Mechanical Overload-Induced Protein Synthesis but Not Muscle Mass

Poster Board Number: E361

Eunbin Jee (Nippon Sport Science University), Yuki Tamura (Nippon Sport Science University, Nippon Sport Science University, Nippon Sport Science University), Karina Kouzaki (Nippon Sport Science University, Nippon Sport Science University), Takaya Kotani (Nippon Sport Science University), Koichi Nakazato (Nippon Sport Science University, Nippon Sport Science University, Nippon Sport Science University, Nippon Sport Science University)

Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme of redox homeostasis and ethanol metabolism. Our recent work has indicated an important role for ALDH2 in regulating muscle homeostasis as well. However, the underlying mechanism and adaptability of ALDH2 in skeletal muscle remain highly elusive. We herein examined whether ALDH2 deficiency modifies mechanical overload-induced muscle hypertrophy and related cellular process. Ten-week-old male ALDH2 knockout (background strain: C57BL/6J) and wild-type littermates were involved in this work. Unilateral synergist ablation (SA; the surgical removal of gastrocnemius and soleus muscles) and sham surgery were performed as an experimental hypertrophy model. Seven days after surgery, plantaris muscles were collected. ALDH2 deficiency augmented SA-induced activation of mTORC1 (a key regulator of muscle anabolism), based on the increase in phosphorylation of p70S6K at Thr389. Concomitantly, higher amounts of puromycin-labeled peptides (a marker of protein synthesis rate) were observed in ALDH2 deficit muscle. These observations suggest that ALDH2 deficiency promotes SA-induced muscle hypertrophy. Unexpectedly, there was no statistical difference in SA-induced muscle hypertrophy between genotypes. To explore potential mechanisms underlying mismatch between protein synthesis signal and muscle size, we conducted RNA-seq experiment. However, we couldn’t detect any notable gene potentially affecting muscle mass between genotypes. In conclusion, ALDH2 deficiency enhances mechanical overload-induced mTORC1 activity and protein synthesis but not muscle mass. Pathways other than protein synthesis and/or post-transcriptional events may dominantly affect muscle mass in ALDH2 deficit mice.

Funding was provided by Nippon Sport Science University Research Grant