Disease relevance of Casp1

• Cytokine response modifier A (CrmA), a gene product of cowpox virus, blocks caspase as well as perforin/granzyme-mediated apoptotic pathways [1].
• Treatment with the caspase inhibitor Z-Asp-CH(2)-DCB prevented SU5416-induced septal cell apoptosis and emphysema development [2].
• Deprivation of serum and glucose, components of ischemia in vivo, resulted in myocyte apoptosis, as determined by nuclear fragmentation, internucleosomal cleavage of DNA, and processing of caspase substrates [3].
• Ordering of ceramide formation, caspase activation, and Bax/Bcl-2 expression during etoposide-induced apoptosis in C6 glioma cells [4].
• ICE-like protease (caspase) is involved in transforming growth factor beta1-mediated apoptosis in FaO rat hepatoma cell line [5].

Psychiatry related information on Casp1

• Changes in caspase expression in Alzheimer's disease: comparison with development and aging [6].
• In a rat excitotoxic model of Huntington's disease in which an excitotoxin is infused into the striatum to activate NMDA receptors, short-term lithium pretreatment is sufficient to protect against DNA damage, caspase activation, and apoptosis of striatal neurons, and this neuroprotection is concurrent with Bcl-2 induction [7].
• However, only a slight effect of the caspase inhibitor across the session was found. z-DEVD-fmk impaired development of some essential components of the two-way active avoidance performance, such as escape reaction, conditioned fear reaction, and inter-trial crossings [8].
• These results indicate an opioid-induced neurotoxic consequence regulated by the NMDAR-caspase pathway, a mechanism that may have clinical implications in opioid therapy and substance abuse [9].

High impact information on Casp1

• Caspase inhibition reduces apoptosis and increases survival of nigral transplants [10].
• The caspase family of cysteine proteases regulates the execution of the mammalian apoptotic cell death program [11].
• Modified peptides, such as acetyl-tyrosinyl-valyl-alanyl-aspartyl-chloro-methylketone (Ac-YVAD-cmk), that specifically inhibit proteases of the caspase family effectively block apoptosis in a plethora of experimental paradigms, such as growth factor withdrawal, excitotoxicity, axotomy, cerebral ischemia and brain trauma [10].
• Here we examined the effects of caspase inhibition by Ac-YVAD-cmk on cell death immediately after donor tissue preparation and on long-term graft survival [10].
• Phosphorylation by protein kinase CK2: a signaling switch for the caspase-inhibiting protein ARC [12].

Chemical compound and disease context of Casp1

• We demonstrated previously that overproduction of nitric oxide (NO) by inducible NO synthase (iNOS) in RVLM, leading to caspase 3-dependent apoptotic cell death, plays a pivotal role in cardiovascular depression during endotoxemia induced by intravenous administration of Escherichia coli lipopolysaccharide [13].
• Caspase activation during hypoxia was blocked bycarbobenzoxy-Val-Ala-Asp-fluoromethyl ketone and overexpression of Bcl-2 [14].
• On the other hand,the serine protease inhibitors did not prevent release of mitochondrialcyt.c during hypoxia, suggesting that these compounds blockeda critical step in post-mitochondrial caspase activation [14].
• The role of PI-3K/PKB in adenosine-induced preconditioning was assessed by monitoring Caspase 3 activity and lactate dehydrogenase (LDH) release induced by exposure of cardiomyocytes to 4 h hypoxia (0.5% O(2)) followed by 18 h reoxygenation (HX4/R) [15].
• Furthermore, melatonin treatment diminished cytochrome c release from mitochondria and reduced caspase 3 and caspase 9 activation induced by hyperhomocysteinemia [16].

Biological context of Casp1

• Further, the time course of caspase 3 activation after glutamate exposure of CGNs parallels the development of apoptosis [17].
• 4) Exposure of primary rat islets or 832/13 cells to the inflammatory cytokines causes cell death as evidenced by the release of adenylate kinase activity into the cell medium, with no attendant increase in caspase 3 activation or annexin V staining [18].
• Expression of interleukin-1 beta converting enzyme gene family and bcl-2 gene family in the rat brain following permanent occlusion of the middle cerebral artery [19].
• Intravitreal injection of a caspase-1 inhibitor, acetyl-tyrosyl-valyl-alanyl-aspartic-aldehyde (Ac-YVAD-CHO), at postnatal days 21 (P21) and P26 was performed to see if this caused a decrease in apoptotic cell number at P28 [20].
• Double-labelling caspase immunohistochemistry and in situ end-labelling of nuclear DNA fragmentation disclosed co-localisation of strong caspase expression and nuclear DNA breaks in a small percentage of neurons but no co-localisation in astrocytes [21].

Anatomical context of Casp1

• Hepatocyte apoptosis, caspase activation, and poly (ADP-ribose) polymerase (PARP) cleavage, which are normally observed in response to both bile acids, were largely prevented after preincubation of hepatocytes with betaine [22].
• To characterize the mechanisms by which apoptosis proceeds in alveolar macrophages during Pcp, specific caspase inhibitors are tested for their ability to suppress the apoptosis [23].
• B cell apoptosis triggered by antigen receptor ligation proceeds via a novel caspase-dependent pathway [24].
• In a rat fibroblast model, we previously observed that caspase inhibition potentiates p53-dependent apoptosis and prevents the Rb cleavage associated with p53 activation [25].
• Akt1 provides a novel capacity to foster EC survival through the prevention of cysteine protease degradation of Bcl-x(L) that is intimately linked to the specific inhibition of caspase 1-, 3-, and 9-like activities and the modulation of mitochondrial membrane potential and cytochrome c release [26].

Associations of Casp1 with chemical compounds

• Our data demonstrate that glutamate-induced apoptosis of CGNs is mediated by a posttranslational activation of the ICE/CED-3-related cysteine protease caspase 3 [17].
• Moreover, glutamate-induced apoptosis of CGNs is almost completely blocked by the selective cell permeable tetrapeptide inhibitor of caspase 3, Ac-DEVD-CHO but not by the ICE (caspase 1) inhibitor, Ac-YVAD-CHO [17].
• In cell-free extracts from brain and liver of Sprague-Dawley rats, caspase was activated by cytochrome c/2'-deoxyadenosine 5'-triphosphate at both neonatal and adult stages [27].
• By injecting the broad spectrum caspase inhibitor BOC-Asp(OMe)-fluoromethyl ketone into the lateral ventricle of adult rats, a 60% ;reduction of terminal deoxynucleotidyl transferase dUTP Nick End Labeling (TUNEL) profiles was observed in all neurogenic regions without changing the number of newly generated cells [28].
• Differential c-Fos and caspase expression following kainic acid excitotoxicity [21].

Physical interactions of Casp1

• The lipid peroxidation product 4-hydroxy-2,3-nonenal increases AP-1-binding activity through caspase activation in neurons [29].

Enzymatic interactions of Casp1

• The AICD (APP intracellular Domain) and C31, caspase-cleaved C-terminal fragment of APP, have been found in Alzheimer's disease (AD) patients' brains and have been reported to induce apoptosis in neuronal cells [30].
• Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces programmed cell death through the caspase activation cascade and translocation of cleaved Bid (tBid) by the apical caspase-8 to mitochondria to induce oligomerization of multidomain Bax and Bak [31].
• The caspase substrate poly(ADP)-ribose polymerase is cleaved by granzyme B in a cell-free assay at two sites that resemble the granzyme B specificity determined by the combinatorial methods [32].
• Immunostaining using tyrosine hydroxylase (TH) and cleaved caspase-3 antibodies demonstrated that caspase-1 and -3 inhibitors reduce caspase-3 activation as well as overall cell death [33].
• Doses of 10, 20, and 40 mg/kg of methamphetamine produced significant increases in calpain- and caspase-cleaved alpha II-spectrin and tau protein fragments, suggesting cell injury or death [34].

Regulatory relationships of Casp1

• Suppressing the activation of caspase-9 inhibited the activation of caspase -3 and enhanced the cell viability and MP [35].
• Overexpression of Bcl-2 inhibited caspase activity and decreased the apoptosis [36].
• p53 can promote mitochondria- and caspase-independent apoptosis [37].
• The general caspase inhibitors BAF and zVAD-FMK inhibited N-terminal caspase-2 processing [38].
• Another group of rats was treated with caspase-1 inhibitor Ac-YVAD-CHO to block IL-18 production [39].

Other interactions of Casp1

• Northern blot analysis revealed a transient induction of Nedd2 mRNA 8 h after the ischemic insult (3.8-fold) and an increase in Yama/CPP32 mRNA 16 to 24 h after the insult (5.8-fold at 24 h), whereas the expression of Ice remained constant [19].
• 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 [20].
• Using an affinity labeling approach to trap activated caspases in situ, we show that caspase 8 is the apical caspase activated following seizures [40].
• In contrast, activation of caspase-1 and caspase-9 was not observed at any of the times studied after STS exposure [41].
• Expression of caspase mRNA and the ratio of Bax to Bcl-2 were evaluated by reverse-transcriptase polymerase chain reaction (RT-PCR) [42].

Analytical, diagnostic and therapeutic context of Casp1

• Western blots of cytosolic extracts from glutamate-exposed CGNs reveal both cleavage of the caspase 3 substrate, poly(ADP-ribose) polymerase, as well as proteolytic processing of pro-caspase 3 to active subunits [17].
• This was accompanied by a decrease in the expression of active caspase 3, as shown by immunohistochemistry [43].
• Concurrent studies were carried out to determine the presence of intracellular reactive oxygen species (ROS) via confocal microscopy, mitochondrial trans-membrane potential by flow cytometry, mitochondrial release of cytochrome c, and the activation of caspase activities in AM by Western blot analysis [44].
• We hypothesized that DOX induces apoptosis through caspase activation in cardiomyocytes, and we examined this hypothesis using both rat primary cultured cardiomyocytes and rat hearts from an animal model [45].
• Finally, the authors demonstrated the caspase-1 transcripts in the epithelia of these tissues by in situ hybridization analyses [46].

References