Environmental Noise, Oxidative Stress, and Transglutaminase Signaling: A Proposed Mechanism Linking Acoustic Stress to Tissue Injury

Environmental noise pollution is increasingly recognized as a major public health concern that extends beyond auditory dysfunction and contributes to cardiovascular, metabolic, and neurological disorders. A growing body of evidence indicates that chronic noise exposure induces oxidative stress, inflammation, mitochondrial dysfunction, and disturbances in intracellular calcium homeostasis, all of which are central mediators of tissue injury. Transglutaminases (TGs) are a family of calcium-dependent enzymes that regulate protein cross-linking, extracellular matrix remodeling, cellular differentiation, and stress adaptation. Among the human TG isoforms, TG1, TG2, TG6, and TG7 have been implicated in oxidative stress responses, neurodegeneration, fibrosis, inflammation, apoptosis, and cancer progression. Despite extensive research on both noise-induced cellular stress and TG biology, the potential relationship between acoustic stress and TG activation remains largely unexplored. This narrative review summarizes the structure, tissue distribution, and pathological functions of stress-responsive TG isoforms, with particular emphasis on TG1, TG2, TG6, and TG7. Furthermore, it examines current evidence linking environmental noise exposure to oxidative stress and calcium dysregulation and proposes a mechanistic framework through which these alterations may promote TG activation. We hypothesize that noise-induced oxidative stress and intracellular calcium imbalance may activate stress-responsive TGs, leading to apoptosis, neurodegeneration, extracellular matrix remodeling, fibrosis, and inflammation, ultimately contributing to tissue injury and organ dysfunction. By integrating current knowledge from TG biology and environmental health research, this review highlights a potentially important but underexplored mechanism of environmental stress-induced pathology and identifies key priorities for future investigation.