Compartment-Specific Remodeling of Superoxide Dismutase Isoforms Reveals Sex-Associated Differences During Experimental Gliomagenesis

Glioma progression is accompanied by alterations in redox homeostasis, yet the coordinated expression of antioxidant enzyme isoforms during tumor development remains incompletely understood. In particular, whether the expression of superoxide dismutase (SOD) isoforms is differentially regulated according to biological sex has received little attention. In this study, we characterized the transcriptional (RT-qPCR) and translational (ELISA) profiles of the three SOD isoforms (SOD1-SOD3) in an N-ethyl-N-nitrosourea (ENU)-induced rat glioma model and evaluated potential sex-associated differences. SOD1 expression remained unchanged at both the mRNA and protein levels in glioma tissue compared with healthy brain, indicating preservation of cytosolic enzyme abundance during tumor development. In contrast, SOD2 was significantly upregulated at both transcriptional and protein levels, with a more pronounced increase in male than in female animals. Conversely, SOD3 showed a significant reduction in both mRNA and protein abundance, although this decrease was less marked in females. These findings demonstrate a compartment-specific pattern of antioxidant remodeling characterized by stable SOD1 expression, increased mitochondrial SOD2, and reduced extracellular SOD3. Because the present study quantified transcript and protein abundance rather than direct reactive oxygen species generation, enzymatic activities, or downstream signaling pathways, the functional implications of these expression changes remain to be established. Nevertheless, the observed sex-associated differences suggest that biological sex influences antioxidant responses during experimental gliomagenesis and support its consideration as an important variable in future mechanistic and translational studies.