Pathological arterial remodeling heavily depends on the aberrant proliferation and migration of vascular smooth muscle cells (VSMCs). This study explores how γ-Glutamylcysteine (γ-GC) regulates VSMC signaling to mitigate hypertensive structural damage.

Objectives: Reactive oxygen and nitrogen species (RONS) act as signalling molecules under physiological conditions; however, how oxidative eustress regulates glucose uptake in skeletal muscle remains poorly defined. We investigated the role of moderate oxidation in skeletal muscle glucose uptake, focusing on AKT/AMPK phosphorylation, GLUT4 translocation and functional glucose uptake. Methods: AKT and AMPK phosphorylation were analysed in C2C12 myoblasts/myotubes exposed to insulin and redox-modulating stimuli associated with oxidative eustress, including hydrogen peroxide, nitric oxide donors and angiotensin II. GLUT4 translocation was assessed by quantitative immunocytochemistry and confocal fluorescence microscopy in cells expressing a GLUT4 reporter. Glucose uptake was evaluated in isolated skeletal muscle fibres using 6-NBDG. Results: Oxidative eustress was associated with increased AKT and AMPK phosphorylation and enhanced GLUT4 translocation to the plasma membrane. Hydrogen peroxide, nitric oxide donors and angiotensin II increased GLUT4 presence at the plasma membrane and enhanced glucose uptake, with hydrogen peroxide showing a dose-dependent effect. Increased glucose uptake was consistent with GLUT4 translocation. Discussion: These findings support oxidative eustress as a physiological redox mechanism linking AKT/AMPK activation, GLUT4 translocation and glucose uptake in skeletal muscle. Redox signalling may therefore contribute to skeletal muscle glucose metabolism.

Spinal cord injury (SCI) causes myelin breakdown and membrane disruption, leading to the release and redistribution of cholesterol, fatty acids, and other lipids within the lesion. The resulting disruption of lipid homeostasis can promote sustained lipid peroxidation, neuroinflammation, and repair failure. In recent years, lipid droplets (LDs) have been recognized as highly dynamic organelles that coordinate lipid storage, mobilization, energy metabolism, and stress responses. However, the stage- and cell-specific roles of LDs in lipid-redox dysregulation after SCI remain poorly understood.

Neuroblastoma (NB) is a common pediatric extracranial solid tumor. Dimethylaminomicheliolide (DMAMCL), a prodrug of Micheliolide (MCL), shows antitumor activity against NB, but its mechanisms remain unclear. This study investigated the antitumor mechanisms of DMAMCL in NB.

Oxidative protein modifications have been linked to several diseases, but the variety and diversity of modifications are less studied.

Due to the proliferative nature of cancer cells, they utilize more dietary extracellular nutrients via one-carbon metabolism for the various metabolic processes, including the synthesis of antioxidants such as glutathione (GSH) and hydrogen sulfide (H2S). Indeed, several studies have found that specific cancer types produce significantly higher levels of GSH and H2S than normal healthy cells, which may serve as a protective mechanism, allowing them to resist stress, survive, and grow. This metabolic heterogeneity, driven by intrinsic and extrinsic factors, contributes to the distinct metabolic characteristics and vulnerabilities of tumor subtypes, which can be exploited to develop anticancer strategies. In this review, we summarize the fundamental roles and regulation of GSH and H2S in normal physiological systems and in the genesis and progression of cancer, their effects on the tumor microenvironment (TME), and their contribution to drug resistance. We also discuss the influences of diet and the gut microbiome on GSH and H2S production, and how cancer cells reprogram their metabolism to grow and survive in a stressful environment by overproducing GSH and H2S.

Collagen is a long-lived protein present in the extracellular matrix of force-bearing tissues. It has a unique amino acid composition of predominantly glycine, proline and hydroxyproline that repeats throughout its characteristic triple helical structure. In the extracellular space, collagen interact first by a non-enzymatic, entropy-driven process given their high hydrophobicity. Then, enzymes, such as lysyl oxidase (LOX), create covalent bonds (i.e. crosslinks) between triple helices, generating reactive oxygen species (ROS) as a byproduct. Moreover, it was recently discovered that collagen itself generates ROS upon stretching. Therefore, given the close proximity of ROS-generating sources, it seems plausible that collagen undergoes non-enzymatic oxidation.