Disease relevance of Casp6

• Furthermore, treatment of neuroblastoma cells with LfcinB induced cleavage of caspase-6, -7 and -9 followed by cell death [1].
• Cloning and expression of rat caspase-6 and its localization in renal ischemia/reperfusion injury [2].
• Caspase 6 expression in the rat hippocampus during epileptogenesis and epilepsy [3].

High impact information on Casp6

• Furthermore, active caspase 6 is capable of processing and activating procaspase 3 in cellular extracts prepared from non-apoptotic CGCs, whereas caspase 3 failed to activate caspase 6 [4].
• Caspase 6 activity initiates caspase 3 activation in cerebellar granule cell apoptosis [4].
• At the time of deprivation, the addition of the irreversible, broad-spectrum caspase inhibitor zVADfmk or the cell permeable, caspase 6 inhibitor CP-VEID-cho can transiently suppress the appearance of apoptosis, including the early appearance of DNA fragmentation [4].
• Temporal regulation of VEID-7-amino-4-trifluoromethylcoumarin cleavage activity and caspase-6 correlates with organelle loss during lens development [5].
• Interestingly, inhibition of caspase-6 blocked TUNEL-negative cell death [6].

Biological context of Casp6

• Induction of both proapoptotic (Bcl2l11, Casp6) and antiapoptotic (Bcl-X) genes, besides suppression of p21, suggest complex cell death/protection-related mechanisms operating early on [7].
• Identification of caspase-6 in rat blastocysts and its implication in the induction of apoptosis by high glucose [8].
• LTP of excitatory postsynaptic potentials at CA1 synapses was significantly enhanced when hippocampal slices were treated with either a pan-caspase inhibitor or a selective inhibitor of caspase-1, but not by an inhibitor of caspase-6 [9].
• Lamin B1 phosphorylation was partly reduced, but its cleavage was completely prevented, despite the presence of active caspase-6, by adding a selective PKC-betas inhibitor, hispidin, to the apoptotic cytoplasms [10].
• The recombinant caspase-6 protein was characterized by expression in bacteria and by transient transfection in mammalian cells [2].

Anatomical context of Casp6

• Seizures rapidly induced cleavage of constitutively expressed caspase-6, followed by elevated VEIDase activity and the proteolysis of lamin A. Neuronal caspase-6 immunoreactivity was markedly upregulated within cortex and hippocampus in relation to bursts of polyspike paroxysmal discharges [11].
• Caspase-6 is detected in all cells of the blastocyst and is excluded from the nucleus [8].
• Thus, a PKC-beta(II) response to VP-16 seems necessary for lamin B1 cleavage by caspase-6 and nuclear lamina dissolution in apoptosing pyF111 fibroblasts [10].
• Since caspase-6 is involved in the degradation of nuclear matrix proteins and in activation of caspase-3, it may play an important role during renal ischemic injury [2].
• METHODS: A rat kidney cortex lambdagt10 cDNA library was screened to isolate the full-length caspase-6 cDNA [2].

Associations of Casp6 with chemical compounds

• These results indicate that the cascades of FADD/caspase-10/caspase-6 and caspase-11/caspase-3 are not related to apoptosis with DEHP treatment [12].
• Caspase 1 (ICE), 2 (Nedd2), 3 (CPP32), 6 (Mch2) and 8 (Mch5, FLICE) expression was examined using immunohistochemistry in the brains of rats and gerbils following systemic administration of kainic acid (KA) [13].
• Desmin is cleaved selectively at a conserved Asp residue in its L1-L2 linker domain (VEMD downward arrow M(264)) by caspase-6 in vitro and in myogenic cells undergoing apoptosis [14].
• RESULTS: The predicted amino acid sequence of rat caspase-6 contains 277 amino acids, with two potential glycosylation sites, an integrin binding site (KGD), the caspase active site pentapeptide QACRG and the caspase family signature, HX2-4(S,C) X4(L,I,V,M,F)2(S,T)HG (HVDADCFVCVFLSHG) [2].
• Caspase 3 activity was markedly increased by the three apoptosis inducers; caspase 6 was only activated by MPS and etoposide, while caspase 8 was not activated by any of these inducers [15].

Other interactions of Casp6

• The activities of caspase-3 and caspase-6 (effector caspases) were higher than those of caspase-8 and caspase-9 (initiator caspases) [16].
• Antioxidative treatment with lipoic acid significantly suppressed apoptosis and down-regulated caspase-6, -8 and -9 activity, as well as expression levels of pro-apoptotic Bcl-2 proteins without changing blood glucose levels [17].
• RT-PCR analyses confirmed that Cr(VI) enhances the expression of c-Jun N-terminal kinase 1, caspase 6, and DNase I precursor but not that of bcl-2 in lung, while none of these genes was overexpressed in the liver of Cr(VI)-treated rats [18].
• We labled additional sections with anti-M30, directed against an epitope formed by caspase 6 digestion of cytokeratin 18 during apoptosis [19].

Analytical, diagnostic and therapeutic context of Casp6

• RT-PCR products, when subcloned and sequenced, provided full-length cDNAs for ICE (1,209 bp) and CPP32 (786 bp) and partial cDNA products for Mch2 (561 bp) and Nedd2 (811 bp) [20].
• Caspase 6 expression was examined using Western blot and immunohistochemistry [3].
• Ischemic preconditioning ameliorated mitochondrial respiratory dysfunction by 50%, reduced reactive oxygen species generation by 38%, and suppressed mitochondrial lipid peroxidation by 36%, resulting in improvement of the mitochondrial membrane potential and prevention of cytochrome c release as well as caspase-6 activation [21].
• Proteolysis and activation of caspases 3 and 7 as determined by immunoblotting and substrate-specific cleavage assay (DEVDase) preceded caspase-6 proteolysis and increased VEIDase activity following STS treatment [22].

References