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Updated: Apr 18, 2026

Measurements of Physiological Stress Responses in C. Elegans
Published on: May 21, 2020
GSK-3β/β-TrCP regulates Nrf2-mediated oxidative stress response in Cristaria plicata
Yile Hu1, Jinhua An1, Han Qiu1
1College of Life Science, Key Laboratory for Aquatic Germplasm Innovation and Utilization of Jiangxi Province, Education Ministry Key Laboratory of Poyang Lake Environment and Resource Utilization, Nanchang University, Nanchang 330031, China.
Abstract:
Nuclear factor erythroid 2-related factor 2 (Nrf2) orchestrates antioxidant and cytoprotective responses. Beyond classical Keap1-dependent redox regulation, Nrf2 activation can occur via the GSK-3β/β-TrCP pathway during Keap1 inhibition. This study investigated this non-canonical pathway in the stress adaptation of the bivalve (Cristaria plicata). We found that the CpGSK-3β and Cpβ-TrCP genes underwent significant changes in the hepatopancreas, gills, and kidneys after immune (LPS, PGN, Poly(I:C)) or oxidative (H2O2) challenges. Knockdown of either gene increased Nrf2 and NQO1 expression. Protein interaction assays confirmed CpGSK-3β/Cpβ-TrCP binding to the Neh6 domain of CpNrf2, with CpGSK-3β phosphorylating this domain in vitro. Overexpression enhanced cellular resistance to H2O2. These findings reveal the conserved physiological significance of the GSK-3β/β-TrCP-Nrf2 axis in molluscan stress responses, providing new insights into redox regulation mechanisms in invertebrates and potential biomarkers for aquatic environmental stress assessment.
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