Caspases: killer proteases

Nicholson, Donald W.; Thornberry, Nancy A.

doi:10.1016/s0968-0004(97)01085-2

Cited by 2,205 publications

(1,620 citation statements)

References 51 publications

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“…F-actin cleavage was temporarily inhibited by pretreating cochleas with a caspase-3 inhibitor. In other studies, caspase-3 has been reported to be responsible for mediating DNA fragmentation by endonucleases in apoptotic cells (Cohen 1997;Nicholson and Thornberry 1997).…”

Section: Discussionmentioning

confidence: 83%

“…Caspases are a family of aspartate-specific cysteine proteases, which exist as latent intracellular zymogens (Miller 1997;Nicholson and Thornberry 1997). To date, at least 14 caspases have been identified and are divided into two groups; apoptotic initiators (caspases-2, -8, -9, and -10) and apoptotic effectors (caspases-3, -6, and -7), based on their putative functions and sequence homologies (Eldadah and Faden 2000).…”

Section: Introductionmentioning

confidence: 99%

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The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

Nicotera

Henderson

2003

JARO - Journal of the Association for Research in Otolaryngolog

168

155

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We previously reported that intense noise exposure causes outer hair cell (OHC) death primarily through apoptosis. Here we investigated the intracellular signal pathways associated with apoptotic OHC death. Chinchillas were exposed to a 4 kHz narrowband noise at 110 dB SPL for 1 h. After the noise exposure, the cochleas were examined for the activity of each of three caspases, including caspase-3, -8, or -9 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleas were further examined for cytochrome c release from mitochondria by immunohistology and for DNA degradation by the TUNEL method. The results showed that the noise exposure triggered activation of caspase-3, an important mediator of apoptosis. The noise exposure also caused the activation of caspase-8 and caspase-9, each of which is associated with a distinct signaling pathway that leads to activation of caspase-3. Caspase activation occurred only in the apoptotic OHCs and not in the necrotic OHCs. These results indicate that multiple signaling pathways leading to caspase-3 activation take place simultaneously in the apoptotic OHCs. In addition to caspase activation, noise exposure caused the release of cytochrome c from mitochondria, resulting in a punctate fluorescence in the cytosol. In contrast to activation of caspases, the release of cytochrome c took place in both apoptotic and necrotic OHCs. Moreover, the release of cytochrome c in a subpopulation of OHCs took place early in the cell death process, prior to any outward signs of necrosis or apoptosis. These data suggest that in this subpopulation there exists a common step that is shared by cell death pathways before entering either necrosis or apoptosis. Lastly, use of the TUNEL assay in combination with PI labeling provides a more accurate discrimination between apoptosis and necrosis.

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Section: Discussionmentioning

confidence: 83%

Section: Introductionmentioning

confidence: 99%

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

Nicotera

Henderson

2003

JARO - Journal of the Association for Research in Otolaryngolog

168

155

View full text Add to dashboard Cite

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“…IL-1b is a known substrate for caspase-1 (Kuida et al, 1995). However, the role of caspase-1 in induction of apoptosis is controversial (Nicholson and Thornberry, 1997). Overexpression of caspase-1 has induced apoptosis in mammalian cells (Miura et al, 1993), whereas mice deficient in IL-1b develop normally, suggesting a less important role of caspase-1 in regulation of cell death during normal embryogenesis (Kuida et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

et al. 2004

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Khat chewing is a widespread habit that has a deep-rooted sociocultural tradition in Africa and the Middle East. The biological effects of khat are inadequately investigated and controversial. For the first time, we show that an organic extract of khat induces a selective type of cell death having all morphological and biochemical features of apoptotic cell death. Khat extract was shown to contain the major alkaloid compounds cathinone and cathine. The compounds alone and in combination also induced apoptosis. Khat-induced apoptosis occurred synchronously in various human cell lines (HL-60, NB4, Jurkat) within 8 h of exposure. It was partially reversed after removal of khat and the effect was dependent on de novo protein synthesis, as demonstrated by cotreatment with cycloheximide. The cell death was blocked by the pan-caspase inhibitor Z-VAD-fmk, and also by submicromolar concentrations of Z-YVAD-fmk and Z-IETD-fmk, inhibitors of caspase-1 and -8, respectively. The 50% inhibition constant (IC 50 ) for khat (200 mg ml À1 )-induced apoptosis by Z-VAD-fmk, Z-YVAD-fmk and Z-IETD-fmk was 8 Â 10 À7 M as compared to 2 Â 10 À8 M and 8 Â 10 À8 M, respectively. Western blot analysis showed a specific cleavage of procaspase-3 in apoptotic cells, which was inhibited by Z-VAD-fmk. The cell death by khat was more sensitively induced in leukaemia cell lines than in human peripheral blood leukocytes. It is concluded that khat induces a rather swift and sensitive cell death by apoptosis through mechanisms involving activation of caspase-1, -3 and -8.

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“…16,17 Owing to the high potency of caspases for the induction of cell death, their activity is tightly controlled at various levels. These proteases are constitutively expressed as inactive proenzymes, which are activated by processing either in an autocatalytic event or in trans by other caspases upon induction of apoptosis.…”

Section: Pcd Displays Diversity In Cellular Phenotypes and In The Undmentioning

confidence: 99%

“…These proteases are constitutively expressed as inactive proenzymes, which are activated by processing either in an autocatalytic event or in trans by other caspases upon induction of apoptosis. 16,18 Importantly, cleavage by caspases may lead to either loss of function or gain of function of an individual substrate, which is determined by its anti-or proapoptotic nature, respectively. 17 Interestingly, various components of the translation machinery are also direct targets for caspases during apoptosis.…”

Section: Pcd Displays Diversity In Cellular Phenotypes and In The Undmentioning

confidence: 99%

DAP5 and IRES-mediated translation during programmed cell death

Marash

Kimchi

2005

Cell Death Differ

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DAP5 (Death Associated Protein 5), also named p97 and NAT1, is a member of the eIF4G family that lacks the eIF4E binding site. Its function was linked to programmed cell death (PCD) based on the seminal finding that a fragment of DAP5/ p97 protein, which acted in a dominant-negative manner, protected against IFN-gamma (IFN-g)-induced cell death. Subsequently, it was found that DAP5 protein is activated during cell death by caspase cleavage, yielding a C-terminaltruncated protein of 86 kDa. The p86 form promotes internal ribosome entry site (IRES)-dependent translation of several mRNAs including Apaf-1, c-myc, XIAP, HIAP2 and DAP5 itself, which carries an IRES element in its 5 0 UTR. The activation of DAP5 IRES creates a positive feedback loop, which results in sustained translation of DAP5 protein during PCD under conditions of reduced cap-dependent translation. DAP5 deficiency prevents embryonic stem (ES) cell differentiation, suggesting a wider range of DAP5 mRNA targets and additional mechanisms that might activate the protein.

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Caspases: killer proteases

Cited by 2,205 publications

References 51 publications

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

The Caspase Pathway in Noise-Induced Apoptosis of the Chinchilla Cochlea

Khat (Catha edulis)-induced apoptosis is inhibited by antagonists of caspase-1 and -8 in human leukaemia cells

DAP5 and IRES-mediated translation during programmed cell death

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