High Expression of Lysophosphatidic Acid Induces Nerve Injury in LSS Patients via AKT Mediated NF-κB p65 Pathway

Abstract

Lumbar spinal stenosis (LSS) is a spinal degenerative disease, complicated with nerve injury. Lysophosphatidic acid (LPA), a kind of glycerophospholipid molecule is elevated in the initial stages of neural injury. This research aimed to investigate the patho-mechanism of nerve injury caused by LPA in LSS patients. Twenty-five LSS patients and fifteen idiopathic scoliosis patients (without neurological symptoms) were recruited from Xianyang Central Hospital of Shanxi Province. We measured the concentration of LPA in cerebrospinal fluid samples of all subjects. Different concentrations (0.1, 1, and 10 mol/L) of LPA were used to stimulate Rat Neurons-spinal cord (RN-SC) cells. The effects of LPA on cell injury was detected by MTT and LDH (lactate dehydrogenase) assay. Cell apoptosis was determined by FCM (flow cytometry) and TUNEL staining. The changes in the expression of key proteins involved in Akt mediated NF-κB p65 pathway intervened by LPA were determined by western blot. RN-SC cells were pretreated with JSH-23 (NF-κB inhibitor) before LPA exposure, followed by cell apoptosis measurement. The concentration of LPA in LSS patients was notably higher than that in control patients (p < 0.01). The level of LPA was positively correlated with the severity of LSS. LPA treatment induced RN-SC cells displaying oval or rounded cell body with degenerated protrusion dose dependently. In addition, LPA decreased RN-SC cell viability and promoted cell apoptosis in a dose-dependent manner. LPA initiated Akt phosphorylation, IKB phosphorylation, and NF-κB nuclear translocation in a dose-dependent manner. However, JSH-23 (NF-κB inhibitor) pre-treatment prevented effects of LPA. The high levels of LPA induced nerve injury by reducing the viability of RN-SC cells and promoted cell apoptosis through Akt mediated NF-κB p65 signaling pathway. LPA might be a new therapeutic target for relieving nerve injury in LSS patients.

Therapeutic effect of paeoniflorin on chronic constriction injury of the sciatic nerve via the inhibition of Schwann cell apoptosis

“…We examined the effects of different drugs on cell activities. According to the cell viability results, TAK-242, JSH23, and paeoniflorin were used at concentrations of 10 μg/ml, 10 μM (Y. T. Chen, Wang, et al, 2021), 10 μM (Zhai, Liang, & Xu, 2021), and 50 μM (Zhang, Yang, et al, 2021), respectively.…”

Lysophosphatidic Acid Induced Apoptosis, DNA Damage, and Oxidative Stress in Spinal Cord Neurons by Upregulating LPA4/LPA6 Receptors

“…Cord Neurons. Under an optical microscope, the cells had a long and spindle-shaped morphology, with long neurites In order to investigate the viability and cytotoxicity of LPA on spinal cord neurons, LDH and MTT tests were used to analyze the LDH release and viability of cells treated with 0, 0.1, 1, 10, and 20 μM LPA for 24 h [10]. The results showed that LPA dose dependently increased LDH release and reduced cell viability compared with the untreated cell.…”

“…Recent studies have found that the level of LPA in the CSF of LSS patients was significantly increased [ 1 ]. Meanwhile, another study found that LPA promoted apoptosis of spinal cord neurons and mediated LSS injury [ 10 ]. However, the molecular mechanisms of LPA involved in LSS remain obscure.…”

Hydrogen Sulfide Interacting with Cannabinoid 2 Receptors during Sciatic Nerve Injury-Induced Neuropathic Pain

“…Oxidative stress and central sensitization are inextricably linked to the development of neuropathic pain and its accompanying mood disorders [ 25 , 26 ]. These associated emotional disorders are also linked with neuroinflammation and high levels of proinflammatory targets such as the nuclear factor κB (NF-κB), of which the activation induces the phosphorylation of kappa-B inhibitor (p-IKBα) in the CNS and PNS [ 27 , 28 ]. Moreover, exogenous melatonin and irisin alleviated neuropathic pain-associated affective disorders and ethanol-induced behavioral deficits by suppressing the NF-κB activation pathway [ 29 , 30 ].…”