Cellular signaling pathways involved in oxidative stress response

Cellular signaling pathways involved in oxidative stress response refer collectively to a network of intracellular signal transduction mechanisms activated by increased levels of reactive oxygen species (ROS) and other oxidants. These include major kinase cascades such as mitogen‑activated protein kinase (MAPK) family members—ERK, JNK, and p38—as well as redox-sensitive transcription factors like nuclear factor kappa B (NF‑κB) and Nrf2. The activation of these pathways can lead to diverse cellular outcomes including cell survival via upregulation of antioxidant defenses or apoptosis through induction of proapoptotic genes. Key enzymatic sources contributing to ROS generation include NADPH oxidase, xanthine oxidase, mitochondrial respiratory chain complexes, among others. Antioxidant systems—both enzymatic like superoxide dismutase and catalase, and nonenzymatic like glutathione—counteract excessive ROS production. These interconnected networks play central roles in maintaining cellular homeostasis but also contribute significantly to pathogenesis when dysregulated. Chronic oxidative stress is implicated in diseases such as cancer, neurodegeneration, cardiovascular disorders, inflammatory conditions, diabetes complications and aging-related dysfunctions[1][2][3]. Because "cellular signaling pathways" is not a discrete molecular entity but an umbrella term for many interacting proteins/pathways responding to oxidative cues—and because therapeutic targeting focuses on individual nodes within this network—the entry does not represent a canonical drug target itself. "Oxidative stress activates the MAPK signaling pathway... ERK both positively and negatively regulates ROS levels... JNK has both prosurvival and proapoptotic roles... p38 activates ATF2/CREB transcription factors promoting apoptosis..." [1] "Cells have developed antioxidant defense mechanisms... The enzymatic antioxidant system includes superoxide dismutase..., glutathione peroxidase..., catalase..., peroxiredoxin..., glutathione S-transferases..." [2] "Stress-sensitive signaling pathways including p38 MAPK and JNK are strongly activated by oxidative stress... common stress‑activated signaling pathways underlie development of late diabetic complications." [3]

Other names

Oxidative stress signaling pathwaysROS-mediated signaling pathwaysRedox signaling cascades