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usEP Induce Regulated Cell Death Mechanisms

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Ultrashort Electric Pulse Effects in Biology and Medicine

Part of the book series: Series in BioEngineering ((SERBIOENG))

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Abstract

Cells employs many different mechanisms for their expiration. The best known and studied regulated cell death mechanism is apoptosis. Cell death subtypes, including regulated cell death (RCD), programmed cell death (PCD), and accidental cell death, are discussed. A discussion on and caution for the use of the term “necrosis” is included. Apoptosis was the earliest RCD mechanism shown in Jurkat cell responses to usEPs as determined by cytochrome c release and caspase activation. This apoptotic cell death was enhanced by usEP-induced supraelectroporation, as electric fields with nanosecond durations and short(fast) rise-fall times passed through the cell, while pulses with microsecond duration go around cells. However, using Jurkat clones that did and did not express APAF-1, which is an essential protein for apoptosome formation as a platform for caspase-9 and caspase-3 activation, it was also shown that usEPs induced caspase-dependent and caspase-independent cell death. A role for caspases depended on the usEP charging intensity with lower usEP impact causing caspase-dependent cell death while higher charging caused caspase-independent cell death. Although a full discussion of all RCD mechanisms is not included, evidence is presented that not all cell types responded to usEP by apoptotic cell death. The presence or absence of Ca2+ has an impact on the RCD mechanisms. Human triple-negative breast cancer cells expressed either or both necroptosis and parthanatos. Necroptosis is sometimes considered regulated necrosis because plasma membrane pores form from intracellular proteins. Finally, usEPs are also shown to induce cell responses downstream of toll-like receptors (TLRs). Considerations for immunogenic cell death (ICD) are also considered.

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Beebe, S.J. (2021). usEP Induce Regulated Cell Death Mechanisms. In: Ultrashort Electric Pulse Effects in Biology and Medicine. Series in BioEngineering. Springer, Singapore. https://doi.org/10.1007/978-981-10-5113-5_9

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