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Triggers Apoptosis (trigger + apoptosi)
Selected AbstractsSulfation of nitrotyrosine: Biochemistry and functional implicationsIUBMB LIFE, Issue 10 2007Ming-Cheh Liu Abstract Nitration of tyrosine, in both protein-bound form and free amino acid form, can readily occur in cells under oxidative/nitrative stress. In addition to serving as a biomarker of oxidative/nitrative stress, elevated levels of nitrotyrosine have been shown to cause DNA damage or trigger apoptosis. An important issue is whether the human body is equipped with mechanisms to counteract the potentially harmful effects of nitrotyrosine. Sulfate conjugation, as mediated by the cytosolic sulfotransferases (SULTs), is widely used for the biotransformation and disposal of a variety of drugs and other xenobiotics, as well as endogenous thyroid/steroid hormones and catecholamine neurotransmitters. Recent studies have revealed that the sulfation of nitrotyrosine occurs in cells under oxidative/nitrative stress, and have pinpointed the SULT1A3 as the responsible SULT enzyme. In this review, we summarized the available information concerning the biochemistry of nitrotyrosine sulfation and the effects of genetic polymorphisms on the nitrotyrosine sulfating activity of SULT1A3. Functional implications of the sulfation of nitrotyrosine are discussed. IUBMB Life, 622-627, 2007 [source] A secreted anti-activator, OspD1, and its chaperone, Spa15, are involved in the control of transcription by the type III secretion apparatus activity in Shigella flexneriMOLECULAR MICROBIOLOGY, Issue 6 2005Claude Parsot Summary Bacteria of Shigella spp. are responsible for shigellosis in humans and use a type III secretion (TTS) system to enter epithelial cells and trigger apoptosis in macrophages. Transit of translocator and effector proteins through the TTS apparatus is activated upon contact of bacteria with host cells. Transcription of ,15 genes encoding effectors is regulated by the TTS apparatus activity and controlled by MxiE, an AraC family activator, and its coactivator IpgC, the chaperone of IpaB and IpaC translocators. Using a genetic screen, we identified ospD1 as a gene whose product negatively controls expression of genes regulated by secretion activity. OspD1 associates with the chaperone Spa15 and the activator MxiE and acts as an anti-activator until it is secreted. The mechanism regulating transcription in response to secretion activity involves an activator (MxiE), an anti-activator (OspD1), a co-anti-activator (Spa15), a coactivator (IpgC) and two anti-coactivators (IpaB and IpaC) whose alternative and mutually exclusive interactions are controlled by the duration of the TTS apparatus activity. [source] Orexins/hypocretins and orexin receptors in apoptosis: a mini-reviewACTA PHYSIOLOGICA, Issue 3 2010M. Laburthe Abstract An unexpected and fascinating aspect of the neuropeptides orexins has recently emerged when it was shown that orexins acting at orexin receptors OX1R or OX2R induce dramatic apoptosis resulting in massive reduction in cell growth in various cancer cell lines. This mini-review will provide the reader with recent findings related to the proapoptotic actions of orexins and the entirely novel mechanism whereby the seven membrane-spanning G-protein-coupled receptor (GPCR) OX1R triggers apoptosis. Recent data show that orexins induce tyrosine phosphorylation of the tyrosine-based motifs , immunoreceptor tyrosine-based inhibitory motif and immunoreceptor tyrosine-based switch motif , in OX1R. These phosphorylations result in the recruitment and activation of the phosphotyrosine phosphatase SHP-2 and subsequent cytochrome c -mediated mitochondrial apoptosis. Finally, this mini-review will also speculate on: (1) the potential importance of tyrosine-based motifs in the large family of GPCRs; (2) the interest of orexin receptors as therapeutic targets in cancer therapy; (3) the possible role of orexin receptor-mediated apoptosis in physiology and pathophysiology in the brain (neurodevelopment, neurodegenerative diseases) and in the periphery. [source] Activation of JNK and PAK2 is essential for citrinin-induced apoptosis in a human osteoblast cell lineENVIRONMENTAL TOXICOLOGY, Issue 4 2009Yu-Ting Huang Abstract The mycotoxin citrinin (CTN), a natural contaminant in foodstuffs and animal feeds, exerts cytotoxic and genotoxic effects on various mammalian cells. CTN causes cell injury, including apoptosis. Previous studies by our group showed that CTN triggers apoptosis in mouse embryonic stem cells, as well as embryonic developmental injury. Here, we investigated the precise mechanisms governing this apoptotic effect in osteoblasts. CTN induced apoptotic biochemical changes in a human osteoblast cell line, including activation of c-Jun N-terminal kinase (JNK), loss of mitochondrial membrane potential, and caspase-3 and p21-activated protein kinase 2 (PAK2) activation. Experiments using a JNK-specific inhibitor, SP600125, and antisense oligonucleotides against JNK reduced CTN-induced activation of both JNK and caspase-3 in osteoblasts, indicating that JNK is required for caspase activation in this apoptotic pathway. Experiments using caspase-3 inhibitors and antisense oligonucleotides against PAK2 revealed that active caspase-3 is essential for PAK2 activation. Moreover, both caspase-3 and PAK2 require activation for CTN-induced apoptosis of osteoblasts. Interestingly, CTN stimulates two-stage activation of JNK in human osteoblasts. Early-stage JNK activation is solely ROS-dependent, whereas late-stage activation is dependent on ROS-mediated caspase activity, and regulated by caspase-induced activation of PAK2. On the basis of these results, we propose a signaling cascade model for CTN-induced apoptosis in human osteoblasts involving ROS, JNK, caspases, and PAK2. © 2008 Wiley Periodicals, Inc. Environ Toxicol, 2009. [source] Betulin induces mitochondrial cytochrome c release associated apoptosis in human cancer cellsMOLECULAR CARCINOGENESIS, Issue 7 2010Yang Li Abstract We examined whether betulin, a naturally abundant compound, has anticancer functions in human cancer cells. The results showed that betulin significantly inhibited cell viability in cervix carcinoma HeLa cells, hepatoma HepG2 cells, lung adenocarcinoma A549 cells, and breast cancer MCF-7 cells with IC50 values ranging from 10 to 15,µg/mL. While betulin exhibited only moderate anticancer activity in other human cancer cells such as hepatoma SK-HEP-1 cells, prostate carcinoma PC-3, and lung carcinoma NCI-H460, with IC50 values ranging from 20 to 60,µg/mL, it showed minor growth inhibition in human erythroleukemia K562 cells (IC50,>,100,µg/mL). We further investigated the mechanism of anticancer activity by betulin, using HeLa cells as an experimental model. Betulin (10,µg/mL) induces apoptotic cell death, as evidenced by morphological characteristics such as membrane phosphatidylserine translocation, nuclear condensation/fragmentation, and apoptotic body formation. A kinetics analysis showed that the depolarization of mitochondrial membrane potential and the release of mitochondrial cytochrome c occurred as early as 30,min after treatment with betulin. Betulin, unlike its chemical derivative betulinic acid, did not directly trigger mitochondrial cytochrome c release in isolated mitochondria. Importantly, Bax and Bak were rapidly translocated to the mitochondria 30,min after betulin treatment. The sequential activation of caspase-9 and caspase-3/-7 and the cleavage of poly(ADP-ribose) polymerase (PARP) were observed behind those mitochondrial events. Furthermore, specific downregulation of either caspase-9, Bax, or Bak by siRNA effectively reduced PARP cleavage and caspase-3 activation. Taken together, the lines of evidence demonstrate that betulin triggers apoptosis of human cancer cells through the intrinsic apoptotic pathway. © 2010 Wiley-Liss, Inc. [source] | ||||||||||