Under conditions of extreme heat stress, the process of autophagy has previously been shown to protect human cells, but the exact body temperature at which autophagic activation occurs is largely unknown. Further, the interplay between autophagy, the heat shock response (HSR), inflammation, and apoptosis have yet to be examined together under temperature conditions representative of human internal body temperatures at rest (37 °C) or under severe heat stress conditions (41 °C). Thus, the purpose of this study was to examine threshold changes in autophagy, the HSR, inflammation, and apoptosis to increasing levels of ex vivo heat stress. Whole blood was collected from 20 young (23 ± 4 years; 10 men, 10 women) physically active participants. Peripheral blood mononuclear cells (PBMCs) were isolated immediately (baseline) and after 90-min of whole blood heating in 37, 39, and 41 °C water baths, representative of normal resting (non-heat stress) as well as moderate and severe heat stress conditions in humans, respectively. At 37 °C, increased autophagic activity was demonstrated, with no change in the HSR, and inflammation. Subsequently, responses of autophagy, the HSR, and inflammation increased with a moderate heat stress (39 °C), with further increases in only autophagy and the HSR under a severe heat stress of 41 °C. We observed no increase in apoptosis under any temperature condition. Our findings show that in human PBMCs, the autophagy and HSR systems may act cooperatively to suppress apoptotic signaling following heat stress, which may in part be mediated by an acute inflammatory response.

中文翻译：

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年轻人外周血单个核细胞离体加热后自噬的调节

在极端热应激条件下，自噬过程先前已被证明可以保护人体细胞，但发生自噬激活的确切体温在很大程度上是未知的。此外，自噬、热休克反应（HSR）、炎症和细胞凋亡之间的相互作用尚未在代表人体内部体温（37°C）或严重热应激条件（41°C）的温度条件下一起检查。 C）。因此，本研究的目的是检查自噬、HSR、炎症和细胞凋亡的阈值变化，以增加离体热应激水平。从 20 名年轻（​​23 ± 4 岁；10 名男性，10 名女性）身体活跃的参与者收集全血。外周血单个核细胞 (PBMC) 立即（基线）和在 37、39 和 41 °C 水浴中加热 90 分钟全血后分离，代表正常休息（非热应激）以及中度和重度分别是人类的热应激条件。在 37 °C 时，自噬活性增加，HSR 和炎症没有变化。随后，自噬、HSR 和炎症的反应随着中等热应激（39°C）而增加，在 41°C 的严重热应激下仅自噬和 HSR 进一步增加。我们观察到在任何温度条件下细胞凋亡都没有增加。我们的研究结果表明，在人类 PBMC 中，自噬和 HSR 系统可能协同作用以抑制热应激后的凋亡信号传导，