Sequential NO Production by Mitochondria and Endoplasmic Reticulum during Induced Apoptosis

Bustamante, Juanita; Bersier, Geraldine; Badin, Romina Aron; Cymeryng, Cora; Parodi, Armando J.; Boveris, Alberto

doi:10.1006/niox.2001.0420

Cited by 62 publications

(38 citation statements)

References 33 publications

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“…Bustamante observed sequential NO production by mitochondria and the ER during apoptosis of rat thymocytes and recognized that NOS activity was associated with the ER membrane [4]. Our Fig.…”

Section: Discussionsupporting

confidence: 58%

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

Lee¹,

Lee²,

Huang³

et al. 2013

J Assist Reprod Genet

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Purpose Previous studies reported that patients with endometriosis had excess nitric oxide (NO) in the reproductive tract and poor embryo development in IVF cycles. This study aims to elucidate the effects of NO on early embryo development. Methods Zygotes from superovulated B6CBF1 mice were cultured to blastocysts in a variety of media. Sodium nitroprusside (SNP) and N G -nitro-L-arginine (LNA) were added to the culture medium as a NO donor and a NO synthase inhibitor, respectively. The localization and fluorescence intensity of S-nitrosylated (SNO) proteins within 2-cell stage embryos were analyzed with confocal microscopy. Apoptosis and ATP production in the blastocysts were measured. Result(s) Subsequent to NO exposure, the SNO proteins mainly colocalized with the mitochondria and endoplasmic reticulum and the intensity of SNO proteins increased. The addition of a quanylate cyclase inhibitor and a cyclic GMP mimic agent induced nonsignificant changes in SNO proteins, whereas addition of a superoxide scavenger or a reduced form of glutathione rescued the embryos from the effects of NO. However, superoxide scavenger supplementation resulted in decreased blastocyst ATP production. Conclusion(s) Elevated NO exerts deleterious effects on embryo development, possibly through protein S-nitrosylation in the mitochondria and endoplasmic reticulum. Including glutathione as a component in the culture medium might counteract this effect.

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Section: Discussionsupporting

confidence: 58%

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

Lee¹,

Lee²,

Huang³

et al. 2013

J Assist Reprod Genet

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“…Enzymes capable of transferring the UDPglucose moiety have been described previously in viruses, bacteria, plants, and animals (12,36,42,53,60). Importantly, though, the L. pneumophila Ugt enzyme is the first example of a glucosyltransferase that is produced by a facultative intracellular parasite.…”

Section: Discussionmentioning

confidence: 99%

“…In the present study, we characterized a novel product of L. pneumophila that possesses UDP-glucosyltransferase activity and modifies a distinct component of eukaryotic host cells. 12,000 ϫ g for 15 min (all centrifugation steps were performed at 4°C), and resuspended in 100 ml of TBS. The cell suspension was subjected to ultrasonication with five 1-min pulses with 2-min intervals between pulses at the high power setting (Techpan, Warsaw, Poland) on ice.…”

mentioning

confidence: 99%

Purification and Characterization of a UDP-Glucosyltransferase Produced by Legionella pneumophila

2003

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Legionella pneumophila is the agent of Legionnaires' disease. It invades and replicates within eukaryotic cells, including aquatic protozoans, mammalian macrophages, and epithelial cells. The molecular mechanisms of the Legionella interaction with target cells are not fully defined. In an attempt to discover novel virulence factors of L. pneumophila, we searched for bacterial enzymes with transferase activity. Upon screening ultrasonic extracts of virulent legionellae, we identified a uridine diphospho (UDP)-glucosyltransferase activity, which was capable of modifying a 45-kDa substrate in host cells. An approximately 60-kDa UDP-glucosyltransferase was purified from L. pneumophila and subjected to microsequencing. An N-terminal amino acid sequence, as well as the sequence of an internal peptide, allowed us to identify the gene for the enzyme within the unfinished L. pneumophila genome database. The intact gene was cloned and expressed in Escherichia coli, and the recombinant protein was purified and confirmed to possess an enzymatic activity similar to that of the native UDP-glucosyltransferase. We designated this gene ugt (UDP-glucosyltransferase). The Legionella enzyme did not exhibit significant homology with any known protein, suggesting that it is novel in structure and, perhaps, in function. Based on PCR data, an enzyme assay, and an immunoblot analysis, the glucosyltransferase appeared to be conserved in L. pneumophila strains but was absent from the other Legionella species. This study represents the first identification of a UDP-glucosyltransferase in an intracellular parasite, and therefore modification of a eukaryotic target(s) by this enzyme may influence host cell function and promote L. pneumophila proliferation.Legionella pneumophila is the principal agent of Legionnaires' disease, a pneumonic illness of humans. This bacterium is a facultative intracellular parasite that invades and proliferates in both professional and nonprofessional phagocytes (54). The host cells for L. pneumophila include freshwater protozoans and human alveolar macrophages and epithelial cells. Bacterial factors that have been identified as crucial for intracellular infection include, among others, the major outer membrane protein (25), Mip (13), Hsp60 (17, 18), PilD and type II protein secretion (4, 43), type IV pili (29, 51), flagella (41), the Dot/Icm type IV protein secretion system, and the products of the enh, lvh, mil, and pmi loci (2,11,14,16,35,49). In addition to these virulence factors, a variety of enzymes have been identified in Legionella cultures, including a lowmolecular-mass cytotoxin (30), a metalloprotease cytolysin (8, 9), phospholipases (3, 4, 6), lipases (3), phosphatases (5, 44) and phosphokinases (45). For many of these activities, the role in virulence is unclear and/or the eukaryotic substrate(s) is unknown. Thus, further studies aimed at identifying and characterizing novel L. pneumophila enzymes should be important for understanding both Legionnaires' disease and bacterial interactions with eukary...

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“…Finally, the thymocyte Caspase-8 and the thymus N Pozzesi et al apoptotic pathway induced by MPS primarily involves the mitochondria but not the endoplasmic reticulum. 65 Other studies have focused on the critical role of caspase-8 in GC-induced thymocyte apoptosis. In one model of in vitro thymocyte apoptosis, caspase-8 inhibition abrogated cytochrome c release, caspase-9 and caspase-3 activation, and apoptosis, suggesting that caspase-8 inhibition can indirectly inhibit caspase-9 and/or that dexamethasone (DEX)-induced caspase-8 activation is upstream of mitochondria.…”

Section: Role Of Caspase-8 In Gc-induced Apoptosis In Thymocytesmentioning

confidence: 99%

Role of caspase-8 in thymus function

et al. 2013

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The thymus is the primary organ responsible for de novo generation of immunocompetent T cells that have a diverse repertoire of antigen recognition. During the developmental process, 98% of thymocytes die by apoptosis. Thus apoptosis is a dominant process in the thymus and occurs through either death by neglect or negative selection or through induction by stress/aging. Caspase activation is an essential part of the general apoptosis mechanism, and data suggest that caspases may have a role in negative selection; however, it seems more probable that caspase-8 activation is involved in death by neglect, particularly in glucocorticoid-induced thymocyte apoptosis. Caspase-8 is active in double-positive (DP) thymocytes in vivo and can be activated in vitro in DP thymocytes by T-cell receptor (TCR) crosslinking to induce apoptosis. Caspase-8 is a proapoptotic member of the caspase family and is considered an initiator caspase, which is activated upon stimulation of a death receptor (e.g., Fas), recruitment of the adaptor molecule FADD, and recruitment and subsequent processing of procaspase-8. The main role of caspase-8 seems to be pro-apoptotic and, in this review, we will discuss about the involvement of caspase-8 in (1) TCR-triggered thymic apoptosis; (2) death receptor-mediated thymic apoptosis; and (3) glucocorticoid-induced thymic apoptosis. Regarding TCR triggering, caspase-8 is active in medullary, semi-mature heat-stable antigen hi (HAS hi SP) thymocytes as a consequence of strong TCR stimulation. The death receptors Fas, FADD, and FLIP are involved upstream of caspase-8 activation in apoptosis; whereas, Bid and HDAC7 are involved downstream of caspase-8. Finally, caspase-8 is involved in glucocortocoid-induced thymocyte apoptosis through an activation loop with the protein GILZ. GILZ activates caspase-8, promoting GILZ sumoylation and its protection from proteasomal degradation.

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Sequential NO Production by Mitochondria and Endoplasmic Reticulum during Induced Apoptosis

Cited by 62 publications

References 33 publications

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

Nitric oxide modulates mitochondrial activity and apoptosis through protein S-nitrosylation for preimplantation embryo development

Purification and Characterization of a UDP-Glucosyltransferase Produced by Legionella pneumophila

Role of caspase-8 in thymus function

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