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

Mediators of Inﬂammation, 2022 · DOI: https://doi.org/10.1155/2022/1818758 · Published: September 30, 2022

Spinal Cord Injury Pain Management Genetics

Simple Explanation

This study investigates how lysophosphatidic acid (LPA) affects spinal cord neurons, particularly in the context of lumbar spinal stenosis (LSS). It examines LPA's impact on cell viability, apoptosis, DNA damage, and oxidative stress in these neurons. The researchers found that LPA (18:1) decreases cellular activity and increases LDH release in spinal cord neurons. They also discovered that a Rho kinase inhibitor, Y-27632, can mitigate LPA-induced apoptosis, DNA damage, and oxidative stress. The study suggests that LPA activates a pathway (Gα12/13–Rho–ROCK2) that leads to apoptosis, DNA damage, and oxidative stress by increasing the presence of LPA4/LPA6 receptors. The inhibitor Y-27632 appears to counteract these effects by reducing LPA4/LPA6 receptors.

Study Duration

Not specified

Participants

23 LSS patients and 13 idiopathic scoliosis patients

Evidence Level

Not specified

Key Findings

1
LPA (18:1) treatment decreases cell viability and increases LDH release in spinal cord neurons, indicating cytotoxicity.
2
The Rho kinase inhibitor Y-27632 attenuates LPA-induced apoptosis, DNA damage, and oxidative stress in spinal cord neurons.
3
LPA activates the Gα12/13–Rho–ROCK2 pathway by upregulating LPA4/LPA6 receptors, leading to apoptosis, DNA damage, and oxidative stress.

Research Summary

The study investigates the effects of LPA on spinal cord neurons, particularly concerning cytotoxicity, apoptosis, DNA damage, and oxidative stress, using an in vitro model. It finds that LPA (18:1) negatively impacts spinal cord neuron health, but these effects can be mitigated by the Rho kinase inhibitor Y-27632. The research identifies LPA4 and LPA6 receptors as key players in LPA-induced neuronal damage, suggesting potential therapeutic targets for LSS.

Practical Implications

Therapeutic Implications

The findings suggest that targeting LPA4/LPA6 receptors or the Gα12/13–Rho–ROCK2 pathway could offer therapeutic strategies for managing spinal cord neuronal injury in LSS patients.

Drug Repurposing

The Rho kinase inhibitor Y-27632, already used clinically for cerebrovascular diseases, may have potential for repurposing in the treatment of LSS-related neuropathic pain and neuronal damage.

Personalized Medicine

Identifying LPA (18:1) as a predominant secretory type in LSS patients could lead to more personalized treatment approaches based on individual LPA profiles.

Study Limitations

1
The study is conducted in vitro, which may not fully replicate the complex in vivo environment of LSS.
2
The specific mechanisms by which LPA4/LPA6 receptors are upregulated remain unclear.
3
The study focuses on LPA (18:1), while other LPA species may also contribute to spinal cord neuronal injury in LSS.

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