Identifying cell death involves several methods focusing on changes within the dying cell. One primary indicator is membrane integrity. Damage to the plasma membrane, the cell's outer boundary, allows molecules like propidium iodide to enter, indicating compromised integrity. Similarly, leakage of lactate dehydrogenase (LDH) into the surrounding environment signals membrane damage (Monks et al., 1988; Mertens et al., 1995). Another approach involves assessing lysosomal membrane integrity using neutral red (Monks et al., 1988; Mertens et al., 1995).
Beyond membrane integrity, other techniques exist for identifying cell death. Recent research highlights the discovery of mechanisms triggering cell self-destruction, opening new avenues for identifying and even manipulating cell death pathways (https://health.ucdavis.edu/news/headlines/researchers-identify-switch-to-activate-cancer-cell-death/2023/10). Researchers have developed methods to detect cell death based on tissue-specific methylation patterns in circulating cell-free DNA (cfDNA) (https://www.pnas.org/doi/abs/10.1073/pnas.1519286113; https://pubmed.ncbi.nlm.nih.gov/26976580/). This minimally invasive approach holds significant promise for various applications.
Furthermore, various methods exist for detecting programmed cell death (apoptosis), including comprehensive analyses comparing detection methods (https://pmc.ncbi.nlm.nih.gov/articles/PMC9308588/). Studies also explore how pathogens manipulate cell death pathways (https://grants.nih.gov/grants/guide/pa-files/PAR-22-223.html) and utilize screening methods to identify compounds affecting cell death processes (https://www.sciencedirect.com/science/article/pii/S1074552108000835; https://www.nature.com/articles/nm.4184). Advanced techniques, such as Death-seq, enable genome-wide screens to identify regulators of cell death and potentially develop senolytic therapies (https://pubmed.ncbi.nlm.nih.gov/37699398/). Finally, additional protocols leveraging nuclear magnetic resonance (NMR) and high-pressure liquid chromatography (HPLC) further aid in detecting cell death-related parameters (https://www.nature.com/articles/cdd200944). A comprehensive guide to studying different types of cell death, including necroptosis, pyroptosis, and ferroptosis, is available at (https://abcam.com/en-us/technical-resources/guides/cell-death-guide).
In summary, identifying cell death requires a multi-faceted approach, employing various techniques depending on the specific context and research aims. The choice of method depends heavily on the type of cell death being studied and the resources available.
