Jul 29, 2021 · U0126 was applied to inhibit ERK, and metformin or 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) was applied to cause AMP-activated protein kinase (AMPK) activation. Paw withdrawal mechanical threshold (PWMT) were calculated to indicate the level of neuropathic pain.

Aug 1, 2023 · Thereby, further exploration demonstrated that the carteolol activates β-arrestin-ERK-NOX4 pathway to increase reactive oxygen species (ROS) production that imposes oxidative stress on energetic metabolism causing a vicious cycle between declining ATP and increasing ROS production and downregulation of NAD + resulting in metabolic disturbance ...

p-Erk-mediated Nox4 upregulation is one of the mechanisms of ROS generation in STZ-treated beta cells. Our results suggest that BKFE protects beta cells against oxidative stress and apoptosis through the deactivation of Erk.

While for the upstream mechanism, the ERK signaling pathway activation may result from inactivation of the AMP-activated protein kinase (AMPK). Clinically, targeting the AMPK-ERK-NOX4 pathway may be an effective strategy to treat obesity-induced hyperalgesia in the future. MATERIALS AND METHODS CCD model and experimental protocols

Apr 1, 2010 · Hypothetical model for the role of Nox4 in OxLDL-mediated macrophage cytotoxicity. OxLDL induces Nox4 expression via the MEK/ERK pathway and is blocked by MEK inhibitors UO126 and PD98059. Knockdown of Nox4 (Nox4 RNAi) protected macrophages from increased ROS production and cell injury.

Our findings demonstrate that ERK1/2, p65, and Nox4 participate in hypoxic downregulation of PPARγ expression and that PPARγ physically interacts with NF-κB p65 in a mutually repressive fashion to reduce PPARγ transcriptional activity.

Aug 1, 2023 · 0.0117% carteolol induces senescence of human corneal endothelial cells (HCEnCs). The carteolol activates β-arrestin–ERK–NOX4 axis to elevate ROS production. The elevated ROS impair DNA and impose oxidative stress (OS) on energy metabolism. The DNA damage elicits senescence of the HCEnCs via DNA damage response pathway.

May 10, 2020 · Inhibition of Erk phosphorylation by treatment with the PD98059 inhibitor or siRNA Erk also blocked the expression of Nox4 induced by STZ treatment. In conclusion, BKFE inhibits Erk phosphorylation, which in turn prevents STZ-induced oxidative stress and beta cell apoptosis.

Jan 15, 2025 · Mechanistic studies revealed that SR9009 significantly inhibited the phosphorylation of ERK and p38, concomitant with reduced α-SMA levels, suppressing TGF-β1-induced NADPH oxidase 4 (NOX4) mRNA expression in NRK-49F cells.

Jun 6, 2008 · We found that suppression of Nox4 attenuated ERK phosphorylation induced by EGF, whereas Nox2 suppression had no material impact (Fig. 1 F). Together, these data implicate endothelial Nox4 as an endogenous source of ROS in …