• Jennifer Lynn Schiefer, Niklas M Wergen, Gerrit Grieb, Mahsa Bagheri, Harun Seyhan, Maria Badra, Marco Kopp, Paul C Fuchs, Joachim Windolf, and Christoph V Suschek.
• Department of Plastic Surgery, Hand Surgery, Burn Center, Merheim Hospital Cologne, University of Witten/Herdecke, Köln, Germany. Electronic address: schieferJ@kliniken-koeln.de.
• Burns. 2024 Aug 1; 50 (6): 156215771562-1577.

AbstractThe cellular mechanisms of burn conversion of heat damaged tissue are center of many studies. Even if the molecular mechanisms of heat-induced cell death are controversially discussed in the current literature, it is widely accepted that caspase-mediated apoptosis plays a central role. In the current study we wanted to develop further information on the nature of the mechanism of heat-induced cell death of fibroblasts in vitro. We found that heating of human fibroblast cultures (a 10 s rise from 37 °C to 67 °C followed by a 13 s cool down to 37 °C) resulted in the death of about 50% of the cells. However, the increase in cell death started with a delay, about one hour after exposure to heat, and reached the maximum after about five hours. The lack of clear evidence for an active involvement of effector caspase in the observed cell death mechanism and the lack of observation of the occurrence of hypodiploid nuclei contradict heat-induced cell death by caspase-mediated apoptosis. Moreover, a dominant heat-induced increase in PARP1 protein expression, which correlated with a time-delayed ATP synthesis inhibition, appearance of double-strand breaks and secondary necrosis, indicate a different type of cell death than apoptosis. Indeed, increased translocation of Apoptosis Inducing Factor (AIF) and Macrophage Migration Inhibitory Factor (MIF) into cell nuclei, which correlates with the mentioned enhanced PARP1 protein expression, indicate PARP1-induced, AIF-mediated and MIF-activated cell death. With regard to the molecular actors involved, the cellular processes and temporal sequences, the mode of cell death observed in our model is very similar to the cell death mechanism via Parthanatos described in the literature.Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.

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