Low-dose lipopolysaccharide protects nerve cells against spinal cord injury via regulating the PI3K–AKT–Nrf2 signaling pathway

Abstract

This study explored the molecular mechanism behind the protective effects from low-dose lipopolysaccharide (LPS) on an in-vitro model of spinal cord injury (SCI). For this, PC12 cells were treated with different concentrations of LPS and the cell counting kit-8 assay was used to measure the toxicity of LPS to the cells. Next, we used immunofluorescence to measure nuclear translocation of Nrf2 in PC12 cells. PC12 cells were then treated with IGF-1 (PI3K agonist) and LY294002 (PI3K inhibitor). An in-vitro model of SCI was then established via oxygen–glucose deprivation/reoxygenation. Rates of apoptosis were measured using flow cytometry and the TUNEL assay. Low-dose LPS increased the expression levels of Nrf2, p-PI3K/PI3K, and p-AKT/AKT, and facilitated nuclear translocation of Nrf2. The activation of PI3K–AKT signaling by IGF-1 significantly increased the expression of Nrf2, whereas inhibition of PI3K–AKT signaling significantly decreased the expression of Nrf2. Low-dose LPS reduced the apoptotic ratio of PC12 cells, decreased the expression levels of caspase 3 and caspase 9, and increased the expression levels of HO-1, NQO1, and γ-GCS. Low-dose LPS also reduced the rate of apoptosis and oxidative stress by activating the PI3K–AKT–Nrf2 signaling pathway. Collectively, the results indicate that PI3K–AKT–Nrf2 signaling participates in the protective effects from low-dose LPS in an in-vitro PC12 cell model of SCI.

An In Situ Assembled Trapping Gel Repairs Spinal Cord Injury by Capturing Glutamate and Free Calcium Ions

“…Li et al found that low-dose lipopolysaccharide protected nerve cells against SCI by regulating the PI3K-AKT-Nrf2 signaling pathway. [26] Studies have reported that curcumin can inhibit the TGFβ-SOX9 and Wnt/mTOR signaling pathways, promote motor function recovery after injury, reduce neuronal apoptosis, and play a neuroprotective role. [27,28] All these studies are consistent with our results, which verified the SCI repair function of PF-SA-GAD.…”

Utility of In Vitro Cellular Models of Low-Dose Lipopolysaccharide in Elucidating the Mechanisms of Anti-Inflammatory and Wound-Healing-Promoting Effects of Lipopolysaccharide Administration In Vivo

“…In PC12 cells, low-dose LPS has been shown to inhibit apoptosis, as evidenced by the downregulation of pro-apoptotic caspase 3 and caspase 9 and the upregulation of anti-apoptotic HO-1, NQO1, and γ-GCS proteins. Low-dose LPS treatment has also been shown to reduce the apoptotic rate and decrease oxidative stress levels by activating the PI3K-AKT-Nrf2 signaling pathway in an in vitro PC12 cell model of SCI [ 45 ]. These results highlight the therapeutic potential of low-dose LPS administration in SCI, although further studies are needed to elucidate the underlying mechanisms beyond beneficial effects.…”

Recent Advances in the Role of Nuclear Factor Erythroid-2-Related Factor 2 in Spinal Cord Injury: Regulatory Mechanisms and Therapeutic Options

“…Interestingly, low-dose LPS can induce a protective cross-tolerance state, which has a protective effect on subsequent injury (Jacob et al, 2016). Studies have shown that low-dose LPS pretreatment has a neuroprotective effect (Longhi et al, 2011;Li et al, 2013), and its mechanism has been proven to be through activation of the PI3K-Akt-Nrf2 signaling pathway, thereby reducing the rate of apoptosis and inhibiting Oxidative stress (Li W. et al, 2021).…”