Activation of Nuclear Factor Erythroid 2-Related Factor 2 Antagonizes the Reactive Oxygen Species Modulator 1-Induced Oxidative Stress in Nucleus Pulposus Cells

Abstract

This study investigates the role of Reactive Oxygen Species Modulator 1 (ROMO1) in oxidative stress within nucleus pulposus (NP) cells and its potential regulation by Nuclear factor erythroid 2-related factor 2 (Nrf2). Intervertebral disc samples from patients were collected, and ROMO1, Nrf2, collagen I/II levels were analyzed to establish their potential connection. Human NP cells were cultured and exposed to H2O2 to induce oxidative stress. To elucidate ROMO1’s impact on NP cell metabolism, NP cells were transfected with ROMO1. Concurrently, Nrf2 activators and inhibitors were used to modulate Nrf2 expression during culturing. Oxidative stress was assessed through CAT and SOD1 gene expression analysis and measurement of cellular reactive oxygen species (ROS) production. NP cell status was determined by evaluating cell viability and collagen I/II expression. Results indicated elevated ROMO1 expression in severe intervertebral disc degeneration (IDD) and after H2O2 treatment. ROMO1 overexpression increased ROS production, suppressed CAT, SOD, and collagen II expression, while elevating collagen I and negatively affecting cell viability. However, Nrf2 activation effectively suppressed ROMO1 expression and protected NP cells from oxidative stress induced by H2O2 or ROMO1. In conclusion, ROMO1 exacerbates oxidative stress and contributes to NP cell degeneration, a process mitigated by Nrf2 activation.