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Necroptosis: Biochemical, Physiological and Pathological Aspects

Pathology & Oncology Research

Abstract

Programmed cell death is a key component of tissue homeostasis, normal development and wide variety of diseases. Conventional view refers to programmed cell death form as caspase-mediated apoptosis while necrosis is considered as an accidental and unwanted cell demise, carried out in a non-regulated manner and caused by extreme conditions. However, accumulating evidences indicate that necrotic cell death can also be a regulated process. The term necroptosis has been introduced to describe a cell death receptor-induced, caspase-independent, highly regulated type of programmed cell death process with morphological resemblance of necrosis. Necroptosis recently has been found to contribute to a wide range of pathologic cell death forms including ischemic brain injury, neurodegenerative diseases and viral infection, therefore a better understanding of the necroptotic signaling machinery has clinical relevance.

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Abbreviations

PCD:

Programmed cell death

LC3:

Microtubule-associated protein light chain 3

CICD:

Caspase-independent cell death

FasL:

(also known CD95L) Tumor necrosis factor ligand superfamily member 6

Fas receptor:

(also known CD95 receptor) Tumor necrosis factor receptor superfamily member 6

TNFα:

Tumor necrosis factor-alpha, tumor necrosis factor

RIPK1:

(also known RIP1) Receptor-interacting protein kinase 1, receptor-interacting serine/threonine-protein kinase 1

TRAIL:

(also known Apo-2L) Tumor necrosis factor-related apoptosis-inducing ligand, tumor necrosis factor ligand superfamily member 10

Nec-1:

Necrostatin-1

TNF-R1:

Tumor necrosis factor receptor 1, tumor necrosis factor receptor superfamily member 1A

TNF-R2:

Tumor necrosis factor receptor 2, tumor necrosis factor receptor superfamily member 1B

TRAIL-R1:

Tumor necrosis factor-related apoptosis-inducing ligand receptor 1, tumor necrosis factor receptor superfamily member 10A

TRAIL-R2:

Tumor necrosis factor-related apoptosis-inducing ligand receptor 2, tumor necrosis factor receptor superfamily member 10B

TRADD:

TNFα receptor-associated death domain protein, tumor necrosis factor receptor type 1-associated death domain protein

TRAF2:

TNFα receptor-associated factor 2, TNF receptor-associated factor 2

TRAF5:

TNFα receptor-associated factor 5, TNF receptor-associated factor 5

IAP-1:

Inhibitor of apoptosis protein 1, baculoviral IAP repeat-containing protein 3

IAP-2:

Inhibitor of apoptosis protein 2, baculoviral IAP repeat-containing protein 2

NEMO:

NF-kappa-B essential modulator

IKK:

IκB kinase

TAK1:

Transforming growth factor β-activated kinase 1

TAB2:

TAK1 binding protein 2

NFkB:

Nuclear factor NF-kappa-B

FADD:

Fas-associated death domain protein

RIPK3:

(also known RIP3) Receptor-interacting protein kinase 3, receptor-interacting serine/threonine-protein kinase 3

DISC:

Death-inducing signaling complex

CYLD:

Ubiquitin carboxyl-terminal hydrolase

RHIM:

RIP homotypic interaction motif

PYGL:

Glycogen phosphorylase

GLUL:

Glutamine synthetase

GLUD1:

Glutamate dehydrogenase 1

ROS:

Reactive oxygen species

NOX-1:

NADPH oxidase 1

BHA:

Butylated hydroxyanisole

ANT:

Adenine nucleotide translocator, ADP/ATP translocase

CYPD:

Cyclophilin D

mPTP:

Mitochondrial permeability transition pore

ATP:

Adenosine triphosphate

APAF1:

Apoptotic protease-activating factor 1

BAK:

Bcl-2 homologous antagonist/killer

BAX:

Bcl-2-like protein 4

DIF-1:

Differentiation-inducing factor

atg1:

Autophagy related 1 homolog gene

zVAD.fmk:

Carbobenzoxy-valyl-alanyl-aspartyl-[O-methyl]- fluoromethylketone

NK cell:

Natural killer cell

CCI:

Controlled cortical impact

TBI:

Traumatic brain injury

NMDA:

N-Methyl-D-aspartate

LDH:

Lactate dehydrogenase

GSH:

Glutathione

AIF:

Apoptosis-inducing factor

PAR:

poly(ADP-ribose)chain

AA:

Arachidonic acid

LOX:

Lypoxigenase

JNK:

c-Jun N-terminal kinase 1, mitogen-activated protein kinase 8

NO:

Nitric oxide

MnSOD:

Superoxide dismutase [Mn]

ACAT:

Acyl-CoA:cholesterol acyltransferase

CHOP:

C/EBP homologous protein

cFLIP:

Cellular FLICE-like inhibitory protein, CASP8 and FADD-like apoptosis regulator

MDR-ABC:

Multi-drug resistant ATP binding cassette

AML:

Acute myeloid leukemia

GM-CSF:

Granulocyte-macrophage colony stimulating factor

CAD:

Caspase-activated DNAse

ICAD:

Inhibitor of CAD

DED:

Death effector domain

cFLIP:

Cellular FLICE-inhibitory protein

ROCK1:

Rho-associated protein kinase 1

RAIDD:

Receptor-interacting protein-associated ICH-1/CED-3 homologous protein with a DD

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Acknowledgements

This work was supported by grant ETT 016/2008 for PIB.

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Correspondence to Zsuzsanna Dunai.

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Dunai, Z., Bauer, P.I. & Mihalik, R. Necroptosis: Biochemical, Physiological and Pathological Aspects. Pathol. Oncol. Res. 17, 791–800 (2011). https://doi.org/10.1007/s12253-011-9433-4

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