p38-dependent Enhancement of Cytokine-induced Nitric-oxide Synthase Gene Expression by Heat Shock Protein 70

Bellmann, Kerstin; Burkart, Volker; Bruckhoff, Joerg; Kolb, Hubert; Landry, Jacques

doi:10.1074/jbc.m000340200

Cited by 50 publications

(36 citation statements)

References 76 publications

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“…This study reveals that eNOS and iNOS expressions are not increased in the left ventricle after hypoxia, whereas nNOS is considerably increased after 1 and 4 hours of hypoxia. eNOS is related to vascular hemodynamics and hypertension (Huang et al 1995), whereas iNOS is related to Hsp70 (Bellmann et al 2000). Their expressions are not modified after hypoxia under present conditions, thereby indicating that a low oxygen supply has no effect on these NO-producing enzymes.…”

Section: Discussionmentioning

confidence: 90%

“…Hypoxia-inducible factor 1␣ (HIF1␣) participates in the immediate early response to oxygen deprivation (Gassmann and Wenger 1997) and triggers the induction of several hypoxia-associated molecules (Agani et al 2002). Among these molecules, it has recently been demonstrated that HIF1␣ is associated with neuronal nitric oxide synthase (nNOS) and (i)Hsp70 is associated with the inducible form (iNOS) (Bellmann et al 2000). Because of the significance of NO released by NOS for vasorelaxation, the study of the expression of the isoforms of NOS, in association with Hsp in the newborn, is important because of its cardioprotective effect.…”

Section: Introductionmentioning

confidence: 99%

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Effects of hypoxia on stress proteins in the piglet heart at birth

Louapre

Grongnet²,

Tanguay

et al. 2005

Cell Stress Chaper

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Hypoxia at birth represents a very stressful event that can result in severe lifelong consequences in different tissues, including those of the heart. Heat shock and other associated stress proteins are involved in cellular protection, but their roles are not clearly defined at the time of birth. Newborn piglets were subjected to 5% oxygen and 95% nitrogen for either 1 or 4 hours. They were allowed to recover over periods of 1 to 68 hours. The relative levels of ␣B-crystallin, HspB8, Hsp20, Hsp27, Hsp60, and Hsp70 as well as nitric oxide synthases (NOS) (endothelial NOS, inducible NOS, neuronal NOS) were examined by Western blot analysis. Surprisingly, ␣B-crystallin expression was drastically increased in animals submitted to hypoxia. The hypoxia-associated factor HIFI␣ was also strongly and rapidly overexpressed. Heme oxygenase 1 was also increased. To a lesser extent, neuronal NOS was also increased in the left ventricle of animals submitted to hypoxia. This work clearly shows that the Hsp chaperone ␣B-crystallin is strongly overexpressed in the left ventricle of animals submitted to hypoxia. This observation dissociates the response to low oxygenation of ␣B-crystallin and other stress-associated proteins including Hsp27, and it indicates that heme oxygenase is not alone among HSPs in its oxygen-related gene expression.

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Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Effects of hypoxia on stress proteins in the piglet heart at birth

Louapre

Grongnet²,

Tanguay

et al. 2005

Cell Stress Chaper

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“…30,31 This may also explain the cardioprotection against contraction failure, because a recent report showed that the structural components of myofibrils, especially in Z bands, are disorganized in failing human heart. 32 In addition, it has also been reported that both the opening of ATP-sensitive potassium channels on mitochondria 33 and nitric oxide 34 are activated or induced by p38 MAPK and also mediate the cardioprotection. Further investigations concerning this issue may reveal the complete cellular mechanisms of cardioprotection afforded by ␤-adrenergic preconditioning or the mechanism of cardioprotection against ischemia/reperfusion injury.…”

Section: Further Downstream Effectors Of P38 Mapkmentioning

confidence: 99%

Cardioprotective Effect Afforded by Transient Exposure to Phosphodiesterase III Inhibitors

et al. 2001

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Background-Phosphodiesterase III inhibitors (PDEIII-Is) improve the hemodynamic status of heart failure via inotropic/vasodilatory effects attributable to the increase in intracellular cAMP level. Direct cardioprotection by PDEIII-Is and its underlying mechanisms, however, have not been identified. We tested the infarct size-limiting effect of PDEIII-Is and the roles of cAMP, protein kinase (PK) A, PKC, and mitogen-activated protein kinase (MAPK) families in open-chest dogs. Methods and Results-Milrinone, olprinone (PDEIII-Is), or dibutyryl-cAMP (db-cAMP) was injected intravenously 30 minutes before 90-minute ischemia, followed by 6 hours of reperfusion. Olprinone was also examined with an intracoronary cotreatment with a PKA inhibitor (H89), a PKC inhibitor (GF109203X), an extracellular signal-regulated kinase kinase (MEK) inhibitor (PD98059), or a p38 MAPK inhibitor (SB203580) throughout the preischemic period. Either PDEIII-Is or db-cAMP caused substantial hemodynamic changes, which returned to control levels in 30 minutes. Collateral flow and percent risk area were identical for all groups. Both PDEIII-Is and db-cAMP increased myocardial p38 MAPK activity during the preischemic period, which was blocked by H89, but not by GF109203X.

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“…The stimuli that activate these signaling cascades are distinct, and the downstream effects can vary greatly between cell types. Studies have shown that the ERK pathway is activated primarily by growth factors, mitogenic stimuli, and tumor promoters (15), whereas environmental stress and inflammatory cytokines stimulate the p38 and SAPK/JNK pathways (5,34,58).…”

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confidence: 99%

Differential Regulation of the Mitogen-Activated Protein Kinases by Pathogenic and Nonpathogenic Mycobacteria

2002

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Mycobacteria are the etiologic agents of numerous diseases which account for significant morbidity and mortality in humans and other animal species. Many mycobacteria are intramacrophage pathogens and therefore the macrophage response to infection, which includes synthesis of cytokines such as tumor necrosis factor alpha (TNF-␣) and production of nitric oxide, has important consequences for host immunity. However, very little is known about the macrophage cell signaling pathways initiated upon infection or how pathogenic mycobacteria may modulate the macrophage responses. Using primary murine bone marrow macrophages, we established that p38 and extracellular signal-regulated kinases 1 and 2 of the mitogen-activated protein kinase (MAPK) pathways are activated upon infection with different species of mycobacteria. However, we observed decreased MAPK activity over time in macrophages infected with pathogenic Mycobacterium avium strains relative to infections with nonpathogenic mycobacteria. Furthermore, macrophages infected with M. avium produced lower levels of TNF-␣, interleukin 1␤, and inducible nitric oxide synthase 2 than macrophages infected with nonpathogenic species. Inhibitor studies indicate that the MAPKs are required for the Mycobacterium-mediated induction of these effector proteins. Our data indicate that MAPKs are activated in macrophages upon invasion by mycobacteria and that this activation is diminished in macrophages infected with pathogenic strains of M. avium, resulting in decreased production of important immune effector proteins. The decreased MAPK activation associated with M. avium infections suggests a novel point of immune intervention by this mycobacterial species.Mycobacterium spp. are intramacrophage pathogens and therefore the engagement of macrophage receptors by mycobacteria is one of the initial steps in the infection process. A macrophage may respond to a mycobacterial infection by secreting cytokines such as tumor necrosis factor alpha (TNF-␣) or interleukin 1␤ (IL-1␤) and by producing reactive oxygen and nitrogen intermediates. These effects, among others, are the end result of activating various macrophage-signaling pathways. However, questions remain regarding which pathways are initiated and/or modulated by a mycobacterial infection. Previous studies have shown that mycobacterial components such as lipoarabinomannan (LAM) can stimulate a macrophage response, resulting in the production and secretion of TNF-␣ and IL-1␤ (1). Studies have also indicated that arabinofuranosyl-terminated LAM isolated from nonpathogenic mycobacteria stimulates a stronger cytokine response in treated macrophages than does mannose-capped LAM (ManLAM) from pathogenic mycobacteria (50, 52). Furthermore, recent work by Ting et al. indicates that human macrophages infected with Mycobacterium tuberculosis are less responsive to gamma interferon, due to a disruption in STAT1 binding to the transcription factor CREB (55). These experiments suggest that mycobacteria and mycobacterial components can modulate...

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p38-dependent Enhancement of Cytokine-induced Nitric-oxide Synthase Gene Expression by Heat Shock Protein 70

Cited by 50 publications

References 76 publications

Effects of hypoxia on stress proteins in the piglet heart at birth

Effects of hypoxia on stress proteins in the piglet heart at birth

Cardioprotective Effect Afforded by Transient Exposure to Phosphodiesterase III Inhibitors

Differential Regulation of the Mitogen-Activated Protein Kinases by Pathogenic and Nonpathogenic Mycobacteria

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