Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in LPS-stimulated RAW 264.7 macrophages

Schildknecht, Stefan; Heinz, Kathrin; Daiber, Andreas; Hamacher, Jürg; Kavaklı, Pınar Akkaş; Ullrich, Volker; Bachschmid, Markus

doi:10.1016/j.bbrc.2005.12.009

Cited by 27 publications

(30 citation statements)

References 52 publications

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“…2, lane 7) demonstrates that this unidentified protein can be selectively nitrated. Similar selective nitration has been reported previously for p130(cas) (130 kDa) from human neuroblastoma SH-SY5Y cells (Saeki and Maeda, 1999), alpha-tubulin (50-55 kDa) from human gliomas and rat brain (Dremina et al, 2005;Fiore et al, 2006), alpha-actinin (100 kDa) from human myocardium (Borbely et al, 2005), and prostaglandin endoperoxide synthase-2 (72 kDa) from RAW 264.7 macrophages (Schildknecht et al, 2006). Yet, although our data indicate that selective nitration by peroxynitrite targets one protein product also in honey bee brain, the cumulative data from the immunohistochemical (Fig.…”

Section: Resultssupporting

confidence: 84%

Cellular senescence in honey bee brain is largely independent of chronological age

Seehuus

Krekling

Amdam

2006

Experimental Gerontology

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Accumulation of oxidative stress-induced damage in brain tissue plays an important role in the pathogenesis of normal aging and neurodegenerative diseases. Neuronal oxidative damage typically increases with age in humans, and also in the invertebrate and vertebrate model species most commonly used in aging research. By use of quantitative immunohistochemistry and Western blot, we show that this aspect of brain senescence is largely decoupled from chronological age in the honey bee (Apis mellifera). The bee is a eusocial insect characterized by the presence of a reproductive queen caste and a caste of functionally sterile female workers that performs various alloparental tasks such as nursing and foraging. We studied patterns of oxidative nitration and carbonylation damage in the brain of worker bees that performed nurse tasks as 8-and 200-day-olds and foraging tasks as 20-and 200-day-olds. In addition, we examined 180-day-old diutinus bees, a stress-resistant temporal worker form that survives unfavorable periods. Our results indicate that nitration damage occurs only at low levels in vivo, but that a 60-kDa protein from honey bee brain is selectively nitrated by peroxynitrite in vitro. Oxidative carbonylation is present at varying levels in the visual and chemosensory neuropiles of worker bees, and this inter-individual variation is better explained by social role than by chronological age.

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Section: Resultssupporting

confidence: 84%

Cellular senescence in honey bee brain is largely independent of chronological age

Seehuus

Krekling

Amdam

2006

Experimental Gerontology

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“…4A). Similar observations were made in RAW 264.7 cells (Schildknecht et al, 2006) and primary rat alveolar macrophages (unpublished), in which a nitration and inactivation of COx-2 was observed. Although not investigated in detail in IMA 2.1 so far, it is likely that a similar mechanism is responsible for the observed effects, since we found that inactivation of COx-2 could be prevented with NOS-2 inhibitors (not shown).…”

Section: Metabolic Capacity Of Ima 21supporting

confidence: 86%

Characterization of mouse cell line IMA 2.1 as a potential model system to study astrocyte functions

Schildknecht

Kirner

Henn

et al. 2012

ALTEX

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“…We detected nitration of COX-II tyrosine residues (29,30) at each time analyzed and in control mice injected with PBS. After LPS administration, uterine nitrated levels were higher than nonmodified COX-II expression (Fig.…”

Section: Participation Of Pgs In Lps-induced Er Effect Of Cox Inhibimentioning

confidence: 99%

Nitric oxide mediates prostaglandins' deleterious effect on lipopolysaccharide-triggered murine fetal resorption

Aisemberg

Vercelli

Billi

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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Genital tract bacterial infections could induce abortion and are some of the most common complications of pregnancy; however, the mechanisms remain unclear. We investigated the role of prostaglandins (PGs) in the mechanism of bacterial lipopolysaccharide (LPS)-induced pregnancy loss in a mouse model, and we hypothesized that PGs might play a central role in this action. LPS increased PG production in the uterus and decidua from early pregnant mice and stimulated cyclooxygenase (COX)-II mRNA and protein expression in the decidua but not in the uterus. We also observed that COX inhibitors prevented embryonic resorption (ER). To study the possible interaction between nitric oxide (NO) and PGs, we administered aminoguanidine, an inducible NO synthase inhibitor. NO inhibited basal PGE and PGF 2␣ production in the decidua but activated their uterine synthesis and COX-II mRNA expression under septic conditions. A NO donor (S-nitroso-N-acetylpenicillamine) produced 100% ER and increased PG levels in the uterus and decidua. LPS-stimulated protein nitration was higher in the uterus than in the decidua. Quercetin, a peroxynitrite scavenger, did not reverse LPS-induced ER. Our results suggest that in a model of septic abortion characterized by increased PG levels, NO might nitrate and thus inhibit COX catalytic activity. ER prevention by COX inhibitors adds a possible clinical application to early pregnancy complications due to infections. embryonic resorption ͉ uteri ͉ decidua ͉ peroxynitrite ͉ sepsis M aternal infections could cause abortion in humans (1, 2), but their mechanism is not clear. Spontaneous and cytokineboosted abortion rates have been linked to exposure to lipopolysaccharide (LPS) in the environment (3). Bacteria could enter the uterus with ejaculate or by intestinal absorption (4). Previously, we developed a mouse model to study LPS-induced pregnancy loss (5). LPS (1 g/g i.p.) injected on day 7 of pregnancy produced 100% embryonic resorption (ER) at 24 h, with fetal expulsion at 48 h. Nitric oxide (NO) produced by inducible NO synthase (iNOS) plays a key role in ER (5). LPS produced systemic effects but did not affect the mothers' survival or future pregnancies.Prostaglandin (PG) biosynthesis is catalyzed by cyclooxygenase (COX) I and II, the later being inducible by proinflammatory agents such as cytokines and LPS (6-8). It is well known that PGs mediate septicemic signs and symptoms of Gram-negative bacterial infections and stimulate contractility of the myometrium (9, 10). Thus, PGs are considered to be effective abortifacients and are important mediators of LPS-induced ER and preterm labor. Silver et al. (11) showed that deciduae from LPS-treated mice produce inflammatory eicosanoids as PGE 2 , PGF 2␣ , and thromboxane B 2 and that indomethacin (Indo), a nonselective COX inhibitor, prevents abortion.A significant body of experimental evidence suggests a relationship between NO and PGs (12, 13), particularly in pathophysiologic events associated with gestation. In our laboratory we found that epidermal...

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Autocatalytic tyrosine nitration of prostaglandin endoperoxide synthase-2 in LPS-stimulated RAW 264.7 macrophages

Cited by 27 publications

References 52 publications

Cellular senescence in honey bee brain is largely independent of chronological age

Cellular senescence in honey bee brain is largely independent of chronological age

Characterization of mouse cell line IMA 2.1 as a potential model system to study astrocyte functions

Nitric oxide mediates prostaglandins' deleterious effect on lipopolysaccharide-triggered murine fetal resorption

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