Abbreviations: HPLC, high performance liquid chromatography; IR, infrared; ID NMR, one-dimensional nuclear magnetic resonance; MS,-mass spectrometry; C[O.sub.2], carbon dioxide; [IC.sub.50], inhibition concentration of 50%; sh, shoulder; NaCl, sodium chloride; HRESIMS, high-resolution electron spray ionisation mass spectrometry; caled, calculated; CD[Cl.sub.3], deuterated chloroform; F1TC, fluorescence isothiocyanate; mRNA, messenger ribonucleic acid; PCR, polymerase chain reaction; Bcl-2, B-cell lymphoma 2;
Caspases 3, 8 and 9, cysteinyl aspartic acid-protease-3, 8 and 9; Hsp70, heat shock protein 70; CAD, caspase-activated DNAse.
Members of the inhibitors of apoptosis (IAP) protein family are E3 ubiquitin ligases and are well known
caspases regulators, characterized by baculoviral IAP repeat domains [38].
Lazebnik, "
Caspases: enemies within," Science, vol.
The researchers determined that Legionella pneumophila bacteria somehow suppress activation of
caspases 4 and 5 in human cells but, if the enzymes are added back into immune cells, they set off the same fusion events--those also seen in mice --that will kill the bacteria.
This can result from decreased proliferation or increased cell death, which is why the investigators also looked at
caspase 8 and
caspase 9.
Caspases (cysteine aspartyl proteases) are upregulated in the lymphocytes of sepsis patients, which may hasten the death of lymphocytes (42).
The exact mechanism of apoptosis induction is still unknown but would be predicted to involve activation of the mitochondrial pathway and subsequent activation of downstream
caspases. Caspase-8 lies at the apex of an apoptotic cascade and initiates mitochondrial activation of downstream
caspase family members.
Caspases, a family of cysteine proteases, play an important role in the execution phase of apoptosis.
Now scientists have identified three small molecules that inhibit the activity of those
caspases, suppressing toxicity and rescuing neurons from cell death in cell culture.
Both pathways finally end up in the level of activation of
caspases for cell death.
A sampling of topics: significance of protein kinase A in cancer, the role of phosphoinositide 3-kinase-Akt signaling in virus infection, MAPK signaling in human diseases, signaling pathways that protect the heart against apoptosis induced by ischemia and reperfusion, apoptosis induction in T-lymphocytes by HIV, inhibitors of apoptosis proteins and
caspases, and the biology of
caspases.
Caspases are a family of cysteine proteases that act in a highly specific proteolytic cascade as part of the inflammatory response and cell death (Thornberry and Lazebnik.
This closely regulated, energy-requiring process can be initiated through 2 different mechanisms, each based on the successive activation of preexisting but dormant cysteine-aspartate proteases, or
caspases (Figure 1).
The activation of
caspases that mediate apoptosis can be measured in the plasma, thus allowing an indirect evaluation of liver damage.
Key words: apoptosis,
caspases, complement C5, complement complex C5b-9, experimental allergic encephalomyelitis, Fas ligand, oligodendrocyte, multiple sclerosis, phosphatidylinositol-3 kinase, T lymphocyte.
