NF-κB modulates ROS/JNK signaling to attenuate apoptosis in largemouth bass hepatocytes during recovery from heat stress

Wenjia Mao

doi:10.1016/j.jtherbio.2026.104444

NF-κB modulates ROS/JNK signaling to attenuate apoptosis in largemouth bass hepatocytes during recovery from heat stress

2026-05-01

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AI

W

Wenjia Mao

G

Genrong Zhang

S

Sicheng Liang

Y

Yi Sun

Z

Zijie Lin

Q

Qufei Ling *

DOI：10.1016/j.jtherbio.2026.104444

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Heat stress (HS) triggers reactive oxygen species (ROS) accumulation and activates stress-responsive signaling pathways, including c-Jun N-terminal kinase (JNK) and nuclear factor kappa B (NF-kappa B) in fish hepatocytes. However, how ROS, JNK, and NF-kappa B interact under HS and recovery remains poorly understood. In this study, we investigated these interactions in largemouth bass primary hepatocytes. First, we examined intracellular ROS levels and activation of JNK and NF-kappa B in hepatocytes immediately after HS (37 degrees C, 2 h) and during recovery (2, 6, 12, and 24 h). ROS levels and phosphorylated JNK significantly increased after HS and remained elevated throughout recovery, while NF-kappa B activation was observed at 6, 12, and 24 h after HS. Next, their regulatory relationship was investigated by pretreating hepatocytes with specific inhibitors prior to HS and allowing a 24-h recovery. JNK inhibitor SP600125 had no effect on ROS accumulation, whereas the ROS inhibitor N-acetylcysteine significantly reduced JNK activation, suggesting that ROS is functionally associated with JNK activation in this context. Furthermore, inhibition of either JNK or ROS significantly suppressed NF-kappa B activation, whereas the NF-kappa B inhibitor BAY11-7082 led to increased ROS accumulation and JNK activation, indicating a possible compensatory mechanism. Finally, we assessed whether these three signaling molecules regulate HSinduced apoptosis in hepatocytes. Inhibiting ROS or JNK reduced apoptosis, increased mitochondrial membrane potential, and decreased Caspase-3 activity. In contrast, NF-kappa B inhibition enhanced apoptosis. Collectively, our findings indicate that NF-kappa B may plays a protective role during HS recovery in fish by attenuating apoptosis through modulation of ROS/JNK signaling.

Keywords:

Heat stress

ROS

JNK

NF-kappa B

Apoptosis

Hepatocytes

Largemouth bass

NF-κB modulates ROS/JNK signaling to attenuate apoptosis in largemouth bass hepatocytes during recovery from heat stress

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