β-Aminoisobutyric acid, L-BAIBA, protects PC12 cells from hydrogen peroxide-induced oxidative stress and apoptosis via activation of the AMPK and PI3K/Akt pathway

Tomomi Minato; Nobuhisa Nakamura; Tomokazu Saiki; Megumi Miyabe; Mizuho Ito; Tatsuaki Matsubara; Keiko Naruse

doi:10.1016/j.ibneur.2021.12.001

β-Aminoisobutyric acid, L-BAIBA, protects PC12 cells from hydrogen peroxide-induced oxidative stress and apoptosis via activation of the AMPK and PI3K/Akt pathway

IBRO Neurosci Rep. 2021 Dec 7:12:65-72. doi: 10.1016/j.ibneur.2021.12.001. eCollection 2022 Jun.

Authors

Tomomi Minato¹, Nobuhisa Nakamura², Tomokazu Saiki³, Megumi Miyabe², Mizuho Ito², Tatsuaki Matsubara², Keiko Naruse²

Affiliations

¹ Department of Clinical Laboratory, Aichi Gakuin University Dental Hospital, Nagoya, Japan.
² Department of Internal Medicine, School of Dentistry, Aichi Gakuin University, Nagoya, Japan.
³ Department of Pharmacy, Aichi Gakuin University Dental Hospital, Nagoya, Japan.

Abstract

β-Aminoisobutyric acid (BAIBA) is a myokine that is secreted from skeletal muscles by the exercise. Recently, increasing evidence has suggested the multifocal physiological activities of BAIBA. In this study, we investigated whether L-BAIBA has protective effects on rat pheochromocytoma (PC12) cells. Cultured PC12 cells were stimulated with L-BAIBA. Western blot analyses revealed that L-BAIBA stimulation significantly increased the phosphorylation of AMPK and Akt. In contrast, no effect was observed on neurite outgrowth by L-BAIBA. To investigate the effects of L-BAIBA on oxidative stress, PC 12 cells were exposed to hydrogen peroxide (H₂O₂) with and without L-BAIBA. Hydrogen peroxide significantly increased reactive oxygen species (ROS) production and apoptosis in PC12 cells. Pretreatment with L-BAIBA suppressed H₂O₂-induced ROS production and apoptosis, which was abolished by the inhibition of AMPK by compound C. On the other hand, the inhibitory effects of L-BAIBA on oxidative stress-induced apoptosis were abolished by the inhibition of both AMPK and PI3K/Akt. In conclusion, we demonstrated that L-BAIBA confers protection against oxidative stress in PC12 cells by activating the AMPK and PI3K/Akt pathways. These results suggest that L-BAIBA may play a crucial role on protection of neuron-like cells and become a pharmacological agent to treat neuronal diseases.

Keywords: AMPK; BAIBA, β-Aminoisobutyric acid; DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; FITC, fluorescein isothiocyanate; GPCR, G protein-coupled receptor; Hydrogen peroxide; MRGPRD, Mas-related G protein-coupled receptor type D; Neuron; Oxidative stress; PGC-1α, peroxisome proliferator-activated receptor gamma coactivator-1-alpha; PI3K/Akt; PPARγ, peroxisome proliferator-activated receptor gamma; ROS, reactive oxygen species; TUNEL, TdT-mediated dUTP nick-end labeling; β-Aminoisobutyric acid (BAIBA).