Disease relevance of CPP32

• Insulin-like growth factor (IGF)-1 suppresses oligodendrocyte caspase-3 activation and increases glial proliferation after ischemia in near-term fetal sheep [1].
• Hypothermia was associated with a significant overall reduction in loss of immature oligodendrocytes in the periventricular white matter (P < 0.001), and neuronal loss in the hippocampus and basal ganglia (P < 0.001), with suppression of activated caspase-3 and microglia (isolectin-B4 positive) [2].
• Placentomes from cloned pregnancies had a significant volume of shed trophoblast and fetal villous hemorrhage, absent in controls, at both gestational age ranges (P < 0.001) that was shown to be apoptotic by activated caspase-3 immunoreactivity [3].

High impact information on CPP32

• Three different mammalian cell lines and three different insect cell lines including Culicoides variipennis (KC) cells were infected with BTV serotype 10, and the key apoptosis indicators of cell morphology, chromosomal DNA fragmentation, and caspase-3 activation were monitored [4].
• Cooling started within 90 minutes of reperfusion was associated with a significant increase in bioactive oligodendrocytes in the intragyral white matter compared with sham cooling (41 +/- 20 vs 18 +/- 11 per field, P < 0.05), increased myelin basic protein density and reduced expression of activated caspase-3 (14 +/- 12 vs 91 +/- 51, P < 0.05) [5].
• Protection was closely associated with reduced expression of both activated caspase-3 and of reactive microglia [5].
• IGF-1 treatment was associated with reduced caspase-3 activation and increased glial proliferation in a similar dose-dependent manner [1].
• There was a 2.2-fold increased expression of caspase-2 p < 0.001 = and a 2.6-fold increased expression of caspase-3 p < 0.001) in failing left ventricles compared to normal samples [6].

Biological context of CPP32

• Apoptosis was detected using the Tdt-mediated nick-end labelling (TUNEL) method and activated caspase-3 immunolabelling [7].
• We also hypothesize that cell death in the ductus wall may involve pathways that are not dependent on caspase-3 or -7 activation [8].
• Lipid peroxidation, caspase-3 immunoreactivity, and pyknosis in late-gestation fetal sheep brain after umbilical cord occlusion [9].
• There were no differences (p > 0.05) in amounts of caspase-3 mRNA in CL on Day 12 or Day 14 of the estrous cycle compared to Day 12 or Day 14 of pregnancy, respectively [10].
• Fas ligand cytokine levels correlated with expression of both caspase-3 and -2, suggesting a link in the apoptotic "death cascade." Caspase-3 activity also bore a close relationship to LV meridional wall stress calculated from echocardiographic and intraventricular pressure measurements [11].

Anatomical context of CPP32

• Caspase-3 was only expressed in oligodendrocytes that showed apoptotic morphology [1].
• After 3 days' recovery, idazoxan infusion was associated with a significant increase in neuronal loss in the hippocampus (P<0.05), expression of cleaved caspase-3 (P<0.05), and numbers of activated microglia (P<0.05) [12].
• Double-labeling revealed caspase-3 immunoreactivity was mainly in neurons, and to lesser extent in astrocytes and oligodendrocytes [9].
• The loss of mitochondrial membrane potential after 18 h, an increase in caspase-9 and caspase-3 activity after 24 h, and the subsequent appearance of TdT-mediated dUTP nick end labeling-positive nuclei were detected in FPASMC after treatment with 50 microM EUK-134 [13].
• Caspase 3, 8, and 9 activities were 1.6-fold, 1.5-fold, and 1.4-fold greater in the newborn postcardioplegic myocardium (P =.04, P =.01, and P =.01, respectively) [14].

Associations of CPP32 with chemical compounds

• Levels of caspase-3 mRNA were approximately 3-fold higher (p < 0.05) in CL at 12 h and 24 h after PGF2alpha in comparison to those levels measured in matched CL from untreated ewes [10].
• We have determined the effects of two 10-min UCO on the distribution of the lipid peroxidation marker 4-hydroxynonenal (4-HNE) and the activated form of the apoptosis marker caspase-3 in the brains of late-gestation fetal sheep [9].
• Instead, NO inhibited lipopolysaccharide-induced apoptosis in these cells by reducing caspase-3-like protease activity [15].
• Activation of caspase-3 in TPEN-treated AEC was inhibited strongly by N-acetylcysteine and partially by vitamin C and vitamin E. These findings suggest that cytoplasmic pro-caspase-3 is positioned near the lumenal surface of AEC where it is under the influence of Zn(2+) and other anti-oxidants [16].

Other interactions of CPP32

• After exposure of cultured lung cells to conditioned media, protein expression assay of the culture medium revealed no TNF-alpha, TNF receptor (TNFR)-1, or TNFR-2, however, cultured cell lysate reveals elevated levels of TNF-alpha, TNFR-1 and caspase-3 in all groups; most occurred in cells incubated in baseline media (p < 0.05) [17].

Analytical, diagnostic and therapeutic context of CPP32

• Previously we have reported the elevated expression of caspase-3 in the same animal model [18].
• However, we also detected the expression of caspase-2 and caspase-3 by Western blotting [6].
• Immunohistochemistry studies of the LH- and FSH-treated follicles indicated that cleaved caspase-3 was predominantly localized to the peripheral theca-interstitial cells (TIC) [19].
• Northern blot analysis of total cellular RNA from ovine CL and a radiolabeled ovine caspase-3 cRNA probe indicated the presence of a single mRNA transcript of approximately 2.5 kilobases [10].
• Biopsies of mammary gland tissue were collected at 50 days after lambing for in situ detection of cell death and RT-PCR analysis of bax, bcl-2, caspase-3 and GST expressions [20].

References