LSD1 regulates autophagy and apoptosis by acting through the PI3K/Akt/mTOR signaling pathway in spinal cord injury

Abstract

Abstract The epigenetic enzyme lysine-specific demethylase 1 (LSD1) can negatively regulate autophagy in nerve injury diseases. Inhibition of LSD1 can enhance autophagy, attenuate apoptosis, and provide effective neuroprotection after spinal cord injury (SCI). However, existing studies have not fully interrogated the specific mechanisms through which LSD1 promotes autophagy and inhibits apoptosis. We tested if LSD1 induces autophagy and apoptosis of neurons after spinal cord injury by regulating the PI3K/Akt/mTOR signaling pathway by using differentiated PC12 cells in LSD1 gene knockdown and drug inhibition experiments. We found that LSD1 knockdown or inhibition decreased the expression of PI3K/Akt/mTOR-related proteins. Stimulation of LSD1 knockdown cells with the pathway activator IGF-1 increased the expression of LSD1, markedly attenuating the originally enhanced autophagy, and increasing apoptosis. We also showed an interaction between LSD1 and P-PI3K proteins using immunoprecipitation experiments.