Apoptosis (Greek: apo - from, ptosis - falling; commonly pronounced with a silent second p) is a process of deliberate life relinquishment by a cell in a multicellular organism. It is one of the main types of programmed cell death (PCD), and involves an orchestrated series of biochemical events leading to a characteristic cell morphology and death. The apoptotic process is executed in such a way as to safely dispose of cell corpses and fragments.

In contrast to necrosis, which is a form of cells death that results from acute cellular injury, apoptosis is carried out in an orderly process that generally confers advantages during an organism's life cycle. For example, the differentiation of fingers and toes in a developing human embryo requires cells between the fingers to initiate apoptosis so that the digits can separate.

Morphological Markers

• cytoplasmic condensation
• blebbing of the plasma membrane
• pyknotic nuclei
• condensed chromatin
• nuclear matrix re-organization.
• nuclear chromatin
• cell fragmentation into corpses
• DNA fragmentation
• exposed phosphatidylserine on the outer leaflet of their plasma membrane
• disruption of the mitochondrial trans-membrane potential. PMID: 8903420, PMID: 15220540

AIF (apoptosis inducing factor)

Annexin V

• used to detect early phases of apoptosis. PMID: 11053912, PMID: 9210526, PMID: 10728376
• membrane staining with annexin V PMID: 9348289

Apolipoprotein C-1

• an novel apoptotic marker that has been implicated in apoptotic human vascular smooth muscle cell death via recruiting a neutral sphingomyelinase (N-SMase)-ceramide pathway. PMID: 16822514

Bax

• a pro-apoptotic protein. PMID: 15024192
• a promoter of apoptosis. PMID: 12373145

Bcl-2

• anti-apoptotic protein with perinuclear expression. PMID: 15668790
• a marker of apoptosis control (anti-apoptosis) PMID: 12085205
• an inhibitor of apoptosis. PMID: 12373145

BM-1/JIMRO

• a marker of apoptosis. PMID: 8191917

BV-2

• specifically recognizes cells undergoing developmental programmed cell death. PMID: 8078937

Caspase-1

• play a crucial role in the triggering and execution of apoptosis in a variety of cell types. PMID: 11985974

Caspase-3 (active)

• a marker of early apoptosis. PMID: 14555502
• a reliable indicator of apoptotic rate, with a favorable comparison against terminal transferase-mediated DNA nick-end labeling (TUNEL) assay. PMID: 16931214
• main executor of apoptosis in somatic cells. PMID: 14656410

CD95 (Fas)/CD95L (FasL)

• apoptotic molecules. PMID: 16813711

cleaved cytokeratin-18 (c-CK18)

• as useful and specific as morphology for identifying apoptotic colonic epithelial cells. PMID: 15684335

Clusterin

• a protein probably related to the process of programmed cell death (apoptosis), was specifically very highly expressed in target fibers. PMID: 8297243
• clusterin is considered as a specific marker of dying cells. PMID: 1430214

Histone

• histone release from chromatin are recognized as hallmarks of apoptosis. PMID: 16531610

NAPO

• NAPO (negative in apoptosis), specifically lost during apoptosis. The anti-NAPO antibody recognizes two nuclear polypeptides of 60 and 70 kD. The antigen is maintained in quiescent and senescent cells, as well as in different phases of the cell cycle, including mitosis. Thus, immunodetection of NAPO antigen provides a specific, sensitive, and easy method for differential identification of apoptotic and nonapoptotic cells. PMID: 11714728

M30

• an early indicator of apoptosis in epithelial cells. PMID: 10782407
• M30 (cytokeratin 18 neo-epitope) specifically labels late apoptotic trophoblast cells, and is a highly reproducible marker for apoptotic trophoblast. PMID: 11162351

OX-42 IR

• may be a good indicator for measuring the cell death in hippocampal regions by KA excitotoxicity. PMID: 16391514

p41

• may serve as a marker of apoptotic cell death. PMID: 11095960

p53

• P53, a marker of apoptosis control. PMID: 12085205

PAI-2

• cleaved plasminogen activator inhibitor 2 (PAI-2) isoform is a biochemical marker of apoptosis in the promyelocytic NB4 cell line. PMID: 7947088

PARP

• an early marker of chemotherapy-induced apoptosis. PMID: 8358726
• PARP is enzymatically cleaved during programmed cell death (apoptosis), so detection of the cleavage products is characteristic for apoptosis. PMID: 16541210

SBDP120

• 120 kDa spectrin breakdown product
• marker for neuronal apoptosis. PMID: 10825575

Single-Stranded DNA

• MAb to single-stranded DNA is a specific and sensitive cellular marker of apoptosis, which differentiates between apoptosis and necrosis and detects cells in the early stages of apoptosis. PMID: 8806443

Survivin

• a 16.5 kDa anti-apoptosis protein, inhibits the two early apoptotic enzymes caspase-3 and caspase-7, thus preventing programmed cell death. PMID: 11851094
• survivin gene is a novel apoptosis inhibitor. PMID: 10561264

TPA

• tissue polypeptide antigen (TPA), may be considered the first marker of apoptosis measured with a fully standardized quantitative method in tumor cytosol. PMID: 10832591

tTG

• tissue transglutaminase (tTG), a marker of apoptosis during treatment and progression of prostate cancer. PMID: 10569613
• tTG cleavage as a valuable biochemical marker of caspase 3 activation during the late execution phase of apoptosis. PMID: 10556977

Ubiquitin

• a protein marker of programmed cell death. PMID: 7529737

Other Apoptosis Markers

• TUNEL Methods
• propidium iodide (PI) binding to DNA allows detection of late apoptotic/necrotic cells. PMID: 11053912
• Cell-free plasma DNA: a marker for apoptosis during hemodialysis. PMID: 16510434 
• Cytosolic labile zinc: a marker for apoptosis in the developing rat brain. PMID: 16420450
• serum cytochrome c is a sensitive clinical marker of apoptosis. PMID: 15800951, PMID: 12859698
• Resting membrane potential as a marker of apoptosis: studies on Xenopus oocytes microinjected with cytochrome c. PMID: 11313704 
• Formation of high molecular mass DNA fragments is a marker of apoptosis in the human leukaemic cell line, U937. PMID: 7844165
• circulating DNA may be a marker of cell death, although its levels likely reflect a complex process involving the interactions of macrophages with dead and dying cells. PMID: 15261342
• plasma DNA is a cell death/tumour marker that should be taken into account in studying the cancerous process in human diseases, and could be helpful for follow-up and management of elderly patients. PMID: 7767913, PMID: 8244049
• Nucleosomes in serum as a marker for cell death. PMID: 11522104