Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:4.1.1.6 (CAD)
 4,420 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A hallmark of apoptosis is the fragmentation of nuclear DNA. Although this activity involves the caspase-3-dependent DNAse CAD (caspase-activated DNAse), evidence exists that DNA fragmentation can occur independently of caspase activity. Here we report on the ability of truncated Bid (tBid) to induce the release of a DNAse activity from mitochondria. This DNAse activity was identified by mass spectrometry as endonuclease G, an abundant 30 kDa protein released from mitochondria under apoptotic conditions. No tBid-induced endonuclease G release could be observed in mitochondria from Bcl-2-transgenic mice. The in vivo occurrence of endonuclease G release from mitochondria during apoptosis was confirmed in the liver from mice injected with agonistic anti-Fas antibody and is completely prevented in Bcl-2 transgenic mice. These data indicate that endonuclease G may be involved in CAD-independent DNA fragmentation during cell death pathways in which truncated Bid is generated.
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PMID:Endonuclease G: a mitochondrial protein released in apoptosis and involved in caspase-independent DNA degradation. 1175 61

Cisplatin [cis-diamminedichloroplatinum (II)]-treated murine peritoneal macrophages interact with L929 cells in vitro in a sequential manner, resulting in the formation of contact between the two cells. This interaction leads to the death of L929 cells by the process of apoptosis. The detailed investigations have suggested the involvement of two different pathways in macrophage-mediated L929 cell apoptosis. It is observed that the induction of apoptosis in L929 cells by cisplatin-treated macrophages is contact dependent and is mediated through Fas-Fas ligand and tumor necrosis factor-tumor necrosis factor receptor 1 pathways. This conclusion was based on the Western blot and immunoprecipitation analysis of Fas-Fas ligand, tumor necrosis factor-tumor necrosis factor receptor 1, Fas-associated death domain and tumor necrosis factor receptor-associated death domain. The Fas-Fas ligand interaction between macrophages and L929 cells increased the expression of Fas-associated death domain, and tumor necrosis factor-tumor necrosis factor receptor 1 interaction between macrophages and L929 cells increased the expression of tumor necrosis factor receptor-associated death domain in L929 cells. The induction of apoptosis in L929 cells was investigated by DNA fragmentation, Annexin V staining and Western blot analysis of Bax, Bcl-2, Bid, cytochrome c, poly(ADP ribose) polymerase, CAD, caspase-8 and caspase-3.
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PMID:Cisplatin-treated murine peritoneal macrophages induce apoptosis in L929 cells: role of Fas-Fas ligand and tumor necrosis factor-tumor necrosis factor receptor 1. 1715 5

Natural killer (NK) cells are the effectors of innate immunity to act as the first line of defense against viruses and tumors. Granzyme H (GzmH) is predicted to evolve from GzmB and constitutively expressed at a high level in human NK cells. It indicates GzmH plays a pivotal role in NK cell mediated cytolysis. However GzmH is defined as an orphan granzyme and its function has less been defined. Here we demonstrate GzmH can induce rapid apoptosis of target cells, which is dependent on caspase activation and mitochondrial damage. GzmH-induced death is characterized by phophatidylserine externalization, nuclear condensation, DNA fragmentation, caspase activation and cytochrome c release that are hallmarks of typical apoptosis. GzmH can directly cleave ICAD to unleash CAD for DNA fragmentation. Moreover, GzmH directly processes Bid to produce the active form tBid leading to cytochrome c release. Therefore, GzmH may play an essential role in caspase-dependent pathogen clearance in the innate immunity that may complement the proapoptotic function of GzmB in human NK cells.
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PMID:Granzyme H induces apoptosis of target tumor cells characterized by DNA fragmentation and Bid-dependent mitochondrial damage. 1776 74