Disease relevance of Casp2

• Taken together, the data suggest that caspase-2 induction and activation are important mediators of delayed neuronal death following transient global ischemia [1].
• Two caspase-2 transcripts are expressed in rat hippocampus after global cerebral ischemia [1].
• After infection with Cre-producing recombinant adenovirus (re-Ad), the expression of caspase-2 was highly induced in PC-Nd cells and presumptive actively processed fragments of caspase-2 were also observed [2].
• Maximal expression of caspase 2 was found at 24 h primarily in the inner nuclear and ganglion cell layers of the retina and localized to ganglion and amacrine neurons [3].
• CONCLUSION: In Cy/Cy kidneys with ADPKD, there was an increase of the proform of caspase-9, an increase in cytochrome c release into the cytosol, and an increase in caspase-2 protein and activity demonstrating involvement of the intrinsic pathway [4].

Psychiatry related information on Casp2

• Changes in caspase-2 and -3 protein levels in Alzheimer's disease (AD) brains were assessed in comparison with their expression in development and aging [5].

High impact information on Casp2

• Ethanol exposure induced a strong increase of caspase-2, -3, -6, -8, and -9 activities, DNA fragmentation, and mitochondrial permeability [6].
• We have shown that overexpression of the caspase 2-binding protein RAIDD induces neuronal apoptosis, acting synergistically with trophic deprivation [7].
• We have previously shown that caspase 2 is essential for apoptosis of trophic factor-deprived PC12 cells and rat sympathetic neurons [8].
• RAIDD overexpression induced caspase 2 CARD- and caspase 9-dependent apoptosis of PC12 cells and sympathetic neurons [8].
• It is highly unlikely that caspase-2, which is a relatively zVAD-fmk-resistant caspase, is mediating etoposide-induced PARP cleavage, as a preferred inhibitor of this caspase could not prevent cleavage [9].

Biological context of Casp2

• Caspase-2, -3, -6 and -9 were activated during apoptosis and caspase-2 inhibitor (Z-VDVAD-FMK) and caspase-3 inhibitor (Z-DEVD-FMK) significantly attenuated the apoptosis [10].
• Finally, intraventricular administration of the caspase-2-like inhibitor (VDVAD-FMK) 30 min before induction of ischemia decreased the number of CA1 neurons staining positively for DNA damage (Klenow-labeling assay) and increased the number of healthy-appearing CA1 neurons (cresyl violet) compared with vehicle-treated controls [1].
• A rat ischemic brain cDNA library was screened, and two splice-variants of caspase-2 mRNA were identified, caspase-2S and caspase-2L, which were highly homologous with the sequences of human and mouse caspase-2S and caspase-2L genes, respectively [1].
• Interestingly, expression of antisense caspase-2 RNA blocked the p55-IC-induced cell death in naive but not in neuronal PC12 cells, whereas the caspase-3-like specific inhibitor Ac-Asp-Glu-Val-Asp-aldehyde partially inhibited this death in neuronal but not in naive cells [11].
• The rat caspase-2 cDNA clones have an open reading frame (ORF) of 452 amino acids (aa) [2].

Anatomical context of Casp2

• RESULTS: TUNEL-positive photoreceptors of RCS rats stained strongly with antibodies against caspase-1 and caspase-2 [12].
• Norepinephrine induces apoptosis in neonatal rat endothelial cells via down-regulation of Bcl-2 and activation of beta-adrenergic and caspase-2 pathways [10].
• This suggests that most of the caspase 2 transcript was in olfactory sensory neurons [13].
• Strong caspase 2 immunoreactivity was found in microglia up to 6 h following KA administration [14].
• We find that apoptosis induced by BCR cross-linking on EBV-negative mature and immature human B cell lines involves the following sequential, required events: a cyclosporin A-inhibitable, likely calcineurin-mediated step; and activation of caspase-2, -3, and -9 [15].

Associations of Casp2 with chemical compounds

• To further characterize the interplay between generation and removal of new cells, we studied the role of caspase 2 (Nedd 2) and 3 (CPP 32) on the basis of the high expression of these cysteine proteases in neurogenic regions [16].
• The aa sequence QACRG containing the active Cys residue, that is necessary for the proteolytic activity of ICE/Ced-3 (caspase) family of proteases, is also conserved in rat caspase-2 [2].
• Rat caspase-2 also has several Asp residues in the amino and carboxyl cleavage regions similar to other caspase family proteins [2].
• Agents previously shown to inhibit caspase-3-like activation, such as bcl-2 and the Cdk inhibitor flavopiridol, also acted upstream of caspase-2 processing [17].
• Treatment with cycloheximide and zVAD-fmk, but not with MK-801, blocked the malonate-induced cleavage of caspase-2 [18].

Regulatory relationships of Casp2

• The general caspase inhibitors BAF and zVAD-FMK inhibited N-terminal caspase-2 processing [17].
• TGF beta1-treatment induced the progressive proteolytic processing of caspase-2 (ICH-1L/Nedd-2), whereas caspase-1 itself did not show any cleavage from the precursor [19].

Other interactions of Casp2

• Northern blot analysis of total RNA samples indicated that gonadotropin-promoted follicular survival was associated with reduced ovarian expression of messenger RNAs encoding Ich-1 and CPP32 [20].
• Caspase activation pathways induced by staurosporine and low potassium: role of caspase-2 [21].
• This elevated activity is the result of the enhanced activation of both intrinsic and extrinsic apoptosis pathways, including activation of caspase 2 and caspase 8 [22].
• Both methods positioned caspase-2 to rat Chr 4 between markers Prss1 and D4Mit5 [23].
• Up-regulation of bcl-2, inhibitor of Apaf-1/caspase-9/caspase-2 cascade of apoptosis, may be related to the fact that no morphological apoptotic change was induced after dosing of 20 mg/kg DEHP [24].

Analytical, diagnostic and therapeutic context of Casp2

• Induction of TUNEL staining and immunoreactivities for caspases-1 and -3 was greatly reduced with GDNF treatment, whereas the reduction of caspase-2 staining was only minimum [25].
• Western blot analysis showed that active forms of caspase-1-like and caspase-2-like proteases were upregulated at P28, concurrent with the peak in TUNEL-positive cells [12].
• We examined the role of caspase-2 in a model of focally evoked limbic seizures with continuous EEG recording [26].
• The numbers of TUNEL- and caspase-2-positive cells were lower in the BDNF-treated group at 6 hours after reperfusion (P<0.01) [27].
• In this paper, we report genetic fine-positioning and radiation hybrid mapping of caspase-2 in the rat [23].

References