Short bouts of heat can induce a hormetic stress response, whereas prolonged or excessive exposure can elicit detrimental effects. We previously demonstrated an increase in autophagic signaling in C2C12 myotubes in response to 1 h of heat at 40 °C. In opposition, longer durations of heat exposure (e.g., 12 and 24 h) lead to an accumulation of autophagasomes and elevations in markers of cellular inflammation, oxidative stress, and apoptosis. Whether a longer, yet moderate, duration of 2 h of heat further enhances autophagic flux and attenuates stress and inflammatory signaling, or transitions the cell toward a dysregulation of autophagy is unclear. In this study, C2C12 myotubes were maintained at 37 °C or exposed to 40 °C (HT) for 2 h, and harvested immediately or following 2, 8, or 24 h of recovery. Two hours of HT immediately increased pAMPK (T172; p = 0.001), and subsequently increased pULK1 (S555) at 2 h of recovery (p = 0.028). LC3 II was increased at 8 h (p = 0.043) and 24 h (p = 0.015) of recovery, whereas p62 was elevated at 2 h (p = 0.002) and 8 h (p < 0.001) of recovery, but returned to baseline by 24 h. In Bafilomycin A1 treated cells, p62 was further increased immediately following HT (p = 0.041). There was also a significant elevation in p-p38 (Thr180/Try182), pJNK (Thr183/Tyr185), and pNFκB (Ser536). These findings suggest that as short as 2 h of heat exposure contributes to cell stress and accumulation of autophagasomes in skeletal muscle.

短时间的热能引起兴奋性应激反应，而长时间或过度暴露会引起有害影响。我们之前证明了 C2C12 肌管中自噬信号在 40°C 下加热 1 小时后的增加。相反，较长时间的热暴露（例如，12 和 24 小时）导致自噬体的积累和细胞炎症、氧化应激和细胞凋亡的标志物升高。较长但中等的 2 小时加热持续时间是否会进一步增强自噬通量并减弱压力和炎症信号，或者使细胞向自噬失调转变尚不清楚。在本研究中，C2C12 肌管保持在 37°C 或暴露于 40°C (HT) 2 小时，并在恢复后立即或 2、8 或 24 小时收获。p  = 0.001)，随后在恢复 2 小时时增加 pULK1 (S555) ( p  = 0.028)。LC3 II 在恢复 8 小时 ( p  = 0.043) 和 24 小时 ( p  = 0.015) 时增加，而 p62 在恢复 2 小时 ( p  = 0.002) 和 8 小时 ( p  < 0.001) 时升高，但恢复到基线到 24 小时。在巴弗洛霉素 A1 处理的细胞中，p62 在 HT 后立即进一步增加（p  = 0.041）。p-p38 (Thr180/Try182)、pJNK (Thr183/Tyr185) 和 pNFκB (Ser536) 也显着升高。这些发现表明，短至 2 小时的热暴露有助于骨骼肌中的细胞应激和自噬体的积累。