Mild stress could help cells to survive more severe environmental or pathophysiological
conditions. In the current study, we investigated the cellular mechanisms which contribute
to the development of stress tolerance upon a prolonged (0-12 h) fever-like (40 °C)
or a moderate (42.5 °C) hyperthermia in mammalian Chinese Hamster Ovary (CHO) cells.
Our results indicate that mild heat triggers a distinct, dose-dependent remodeling
of the cellular lipidome followed by the expression of heat shock proteins only at
higher heat dosages. A significant elevation in the relative concentration of saturated
membrane lipid species and specific lysophosphatidylinositol and sphingolipid species
suggests prompt membrane microdomain reorganization and an overall membrane rigidification
in response to the fluidizing heat in a time-dependent manner. RNAseq experiments
reveal that mild heat initiates endoplasmic reticulum stress-related signaling cascades
resulting in lipid rearrangement and ultimately in an elevated resistance against
membrane fluidization by benzyl alcohol. To protect cells against lethal, protein-denaturing
high temperatures, the classical heat shock protein response was required. The different
layers of stress response elicited by different heat dosages highlight the capability
of cells to utilize multiple tools to gain resistance against or to survive lethal
stress conditions.
