Human body temperature limits below 40°C during heat stroke or fever. The implications of prolonged exposure to the physiologically relevant temperature (40°C) on cellular mechanobiology is poorly understood. Here, we have examined the effects of heat stress (40°C for 72 h incubation) in human lung adenocarcinoma (A549), mouse melanoma (B16F10), and non-cancerous mouse origin adipose tissue cells (L929). Hyperthermia increased the level of ROS, γ-H2AX and HSP70 and decreased mitochondrial membrane potential in the cells. Heat stress impaired cell division, caused G1 arrest, induced cellular senescence, and apoptosis in all the tested cell lines. The cells incubated at 40°C for 72 h displayed a significant decrease in the f-actin level and cellular traction as compared with cells incubated at 37°C. Also, the cells showed a larger focal adhesion area and stronger adhesion at 40°C than at 37°C. The mitotic cells at 40°C were unable to round up properly and displayed retracting actin stress fibers. Hyperthermia down-regulated HDAC6, increased the acetylation level of microtubules, and perturbed the chromosome alignment in the mitotic cells at 40°C. Overexpression of HDAC6 rescued the cells from the G1 arrest and reduced the delay in cell rounding at 40°C suggesting a crucial role of HDAC6 in hyperthermia mediated responses. This study elucidates the significant role of cellular traction, focal adhesions, and cytoskeletal networks in mitotic cell rounding and chromosomal misalignment. It also highlights the significance of HDAC6 in heat-evoked senile cellular responses.
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Cover Image
Cover Image
Tumor organoids are a relevant, 3-dimensional, culture method which allows long-term growth preserving the stem cell identity and reconstituting to some extent the morphological and phenotypic heterogeneity of the original tumor. Representative fluorescence image of a tumour organoid derived from patient derived GSCs after 23 days of culture, stained for anti-αTubulin (microtubules, white) and Phalloidin (actin red). In this issue Pinto and colleagues (pp. 21–39) observed that different types of cell protrusions (TMs and TNTs) connecting cells were present and coexist inside the organoid. The image was captured by Inés Saenz-de-Santa-Maria with an inverted confocal microscope LSM700, Pln-Apo 10X/0.45 objective.
Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells
Nikita Mundhara, Abhijit Majumder, Dulal Panda; Hyperthermia induced disruption of mechanical balance leads to G1 arrest and senescence in cells. Biochem J 15 January 2021; 478 (1): 179–196. doi: https://doi.org/10.1042/BCJ20200705
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