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Table 2 Markers used for differentiation between apoptosis and necroptosis in the experimental settings

From: Targeting necroptosis as therapeutic potential in chronic myocardial infarction

  Apoptosis Necroptosis References
Morphology Cytoplasmic shrinkage
Chromatin condensation (pyknosis)
Nuclear fragmentation (karyorrhexis)
Plasma membrane blebbing (zeiosis)
Shedding of apoptotic bodies
Increasingly translucent cytoplasm
Swelling of organelles
Membrane permeabilization
Increased cell volume (oncosis)
Mild chromatin condensation (nuclei remain intact)
[11, 13, 20, 71, 73, 87]
Death execution events Caspase-3 execution pathway causes cell shrinkage, chromosomal condensation and DNA fragmentation MLKL phosphorylation and translocation to the plasma membrane causes membrane permeabilization [11,12,13, 20, 27, 71, 73, 87, 88]
Death regulatory factors BID, BAX, Bcl-2, Cytochrome c APAF1, FADD, Caspase-8, Caspase-9 RIPK1, RIPK3 [11,12,13, 20, 27, 58, 71, 73, 87, 88]
Death execution factors Caspase-3
Caspase-7
p-MLKL [11,12,13, 20, 27, 58, 71, 73, 87, 88]
Methods for evaluation in cardiomyocytes TUNEL assays
DNA laddering
Annexin V positive
Caspase-3/7 activity assay
PI staining (staining with impermeant dyes)
HMGB1 release
LDH assay
Detection of RIPK1, RIPK3 and MLKL
[71, 87]
  1. APAF1, Apoptotic protease activating factor 1; Bax, BCL2 associated X protein; BCL-2, B-cell lymphoma 2 protein; BID, BH3-interacting domain death agonist; FADD, Fas-associated protein with death domain; HMGB1, high mobility group box 1; LDH, Lactate dehydrogenase; MLKL, Mixed lineage kinase domain like pseudokinase; p-MLKL, the phosphorylated form of mixed lineage kinase domain like pseudokinase; RIPK1, receptor-interacting serine/threonine-protein kinase 1; RIPK3, receptor-interacting serine/threonine-protein kinase 3; TUNEL, terminal deoxynucleotidyl transferase dUTP nick end labeling