細胞死

レビュー記事：Cell Death Vol. 361:(16) 1570-1583 Oct. 15,2009

細胞死には、apoptosisとnecrosisという古典的分類が広まっている。autophagyは、細胞死の3番目の形として提案されている。これは、細胞がエネルギー産生し、自己器官・macromoleculeの貪食するプロセスであり、生存のために細胞を飢餓状態にし、growth factorを奪う過程である。
しかし、栄養を長期間受け取れない細胞は、すべての成分を消化し、死滅する（autophagy-associated cell death）
apoptosis、necrosis、autophagyの区別は、死滅モード、形態、生化学、分子的関与の違いである。




Programmed cell death は重要なコンセプトで、細胞死は、遺伝的にコントロールされているなら、再送死は”programmed"である。

細胞死が遺伝的にコントロールされたプロセスであるという認識が、多くの疾患メカニズムの解明に役立った。そして、薬物開発が推進された（Thompson CB. Apoptosis in the pathogenesis and treatment of disease. Science 1995;267:1456-1462. 、Reed JC. Drug insight: cancer therapy strategies based on restoration of endogenous cell death mechanisms. Nat Clin Pract Oncol 2006;3:388-398.、Green DR, Kroemer G. Pharmacological manipulation of cell death: clinical applications in sight? J Clin Invest 2005;115:2610-2617.）。

その後、現在、necrosisは、programmed control mechanism下により開始、modulateされている認識となっている。

各種定義、下手な訳より・・・原文の方がわかりやすいだろうと・・・

Apoptosis：定義

Apoptosis is derived from an ancient Greek word that suggests "leaves falling from a tree."

In contrast to the swelling of the cell and its organelles that defines necrosis, the principal morphologic feature of apoptosis is shrinkage of the cell and its nucleus
The distinction between necrosis and apoptosis is due in part to differences in how the plasma membrane participates in these processes.
In necrosis, early loss of integrity of the plasma membrane allows an influx of extracellular ions and fluid, with resultant swelling of the cell and its organelles.
In apoptosis, plasma-membrane integrity persists until late in the process.
A key feature of apoptosis is cleavage of cytoskeletal proteins by aspartate-specific proteases, which thereby collapses subcellular components.
Other characteristic features are chromatin condensation, nuclear fragmentation, and the formation of plasma-membrane blebs.

Autophagy：定義

The word "autophagy," which is derived from the Greek "to eat" ("phagy") oneself ("auto"), was first used for structures that were observed on electron microscopy and that consisted of single-or double-membrane lysosomal-derived vesicles containing cytoplasmic particles, including organelles, in various stages of disintegration.
We now understand that autophagy is the process by which cells recycle their own nonessential, redundant, or damaged organelles and macromolecular components.

It is an adaptive response to sublethal stress, such as nutrient deprivation, that supplies the cell with metabolites it can use for fuel. Autophagy also has a role in the suppression of tumor growth, deletion of toxic misfolded proteins, elimination of intracellular microorganisms, and antigen presentation.

Necrosis:定義

Necrosis (from the Greek "nekros," for corpse) is best defined by light or electron microscopic detection of cell and organelle swelling or rupture of surface membranes with spillage of intracellular contents.
The term "oncosis" (Greek for swelling) is preferred by some investigators, and "oncotic necrosis" has also been used.
The compromise of organellar membranes allows proteolytic enzymes to escape from lysosomes, enter the cytosol, and cause cell demolition.
Necrosis usually results from metabolic failure that has coincided with rapid depletion of ATP; it classically occurs in ischemia.
Necrosis is usually considered an accidental (i.e., nonprogrammed) form of cell death that occurs in response to acute hypoxic or ischemic injury, such as myocardial infarction and stroke.
It occurs spontaneously in neoplasms when cell proliferation outpaces angiogenesis. The exposure of cells to supraphysiologic conditions (e.g., mechanical force, heat, cold, and membrane-permeabilizing toxins) also precipitates necrosis.