Expression of Nitric Oxide Synthase Isoforms and Nitric Oxide Production in Acute Pancreatitis and Associated Lung Injury

Ang, Abel Damien; Adhikari, Subash; Ng, Siaw Wei; Bhatia, Madhav

doi:10.1159/000178886

Cited by 30 publications

(26 citation statements)

References 46 publications

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“…In addition, treatment with SB216763 and TDZD-8 increased phospho-GSK3β-Ser 9 in the TNF groups. Similarly, in a variety of models for inflammation, SB216763 and TDZD-8 have been shown to increase phospho-GSK3β-Ser 9 associated with decreased GSK3β activity via yet to be described pathways (Aberle et al, 1997; Ang et al, 2009; Bove et al, 2001; Daugherty and Gottardi, 2007; Eldar-Finkelman et al, 2009; Johnson and Ferro, 1996; Neumann et al, 2006); however, inhibition of GSK3β-Ser 9 dependent activation of PP2a may prevent the feed-forward continued activation of GSK3β.…”

Section: 0 Discussionmentioning

confidence: 99%

Tumor necrosis factor-α induces increased lung vascular permeability: A role for GSK3α/β

Barton-Pai

Feleder

Johnson

2011

European Journal of Pharmacology

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We tested the hypothesis that glycogen synthase kinase 3α/β (GSK3α/β) modulates tumor necrosis factor-a (TNF) induced increased lung vascular permeability. Rats were treated with TNF (i.v., ~100 ng/ml) or vehicle 0.5 h, 4.0 h and 24.0 h prior to lung isolation. Rats were co-treated with the GSK3α/β inhibitors SB216763 (0.6 mg/kg) or TDZD-8 (1.0 mg/kg). After TNF, the isolated lung was assessed for hemodynamics, wet-dry/dry weight (W-D/D) and extravascular albumin. Extravascular albumin significantly increased at TNF-24 h compared to Control. In the GSK3α/β-inhibited +TNF groups, extravascular albumin was similar to the Control and respective SB216763 and TDZD-8 groups. In separate studies, to assess GSK3α/β-activity, lung lysate was assessed for phospho-GSK3α/β-Ser21/9, total GSK3α/β, un-phospho-β-catenin-Ser33/37and total β-catenin. In the TNF-4.0 h group, there was no change in GSK3α/phospho-GSK3α-Ser21 but there was an increase in GSK3β/GSK3β-Ser9 compared to Control, indicating GSK3β activation at TNF-4.0 h. GSK3β activation was verified because there was a decrease in un-phospho-β-catenin-Ser33/37/β-catenin in the TNF- 4.0 group, a specific outcome for GSK3β activation. In the SB216763+TNF group, un-phospho-β-catenin-Ser33/37 was similar to Control, indicating prevention of TNF-induced GSK3β activation. In the TNF-24 h group, there were increases in the biomarkers of inflammation phospho-eNOS-Ser 1117 and oxidized protein, which did not occur in the SB216763+TNF-24 h and TDZD-8+TNF-24 h groups. In the SB216763+TNF-24 h and TDZD-8+TNF-24 h groups, un-phospho-β-catenin-Ser33/37 was greater than in the Control, indicating continued inhibition of GSK3β. The data indicates that pharmacologic inhibition of GSK3β inhibits TNF induced increased endothelial permeability associated with lung inflammation.

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Section: 0 Discussionmentioning

confidence: 99%

Tumor necrosis factor-α induces increased lung vascular permeability: A role for GSK3α/β

Barton-Pai

Feleder

Johnson

2011

European Journal of Pharmacology

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“…Abbreviations: ERK1/2: extracellular regulated kinase ; GCL: glutamate cysteine ligase; GSH: Reduced glutathione; RNApol: RNA polymerase II; RNAse: ribonuclease. tion, which suggests different roles for each NOS isoform [178]. Acute pancreatitis also provoked deleterious effects on endothelium-dependent relaxing response for acetylcholine (Ach) in vitro and on haemodynamic parameters, which were associated with high plasma nitrite/nitrate levels as consequence of intense inflammatory responses [179].…”

Section: Nitrosative Stress In Acute Pancreatitismentioning

confidence: 99%

Cross-Talk between Oxidative Stress and Pro-Inflammatory Cytokines in Acute Pancreatitis: A Key Role for Protein Phosphatases

Escobar

Pereda²,

Arduini³

et al. 2009

CPD

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Acute pancreatitis is an acute inflammatory process localized in the pancreatic gland that frequently involves peripancreatic tissues. It is still under investigation why an episode of acute pancreatitis remains mild affecting only the pancreas or progresses to a severe form leading to multiple organ failure and death. Proinflammatory cytokines and oxidative stress play a pivotal role in the early pathophysiological events of the disease. Cytokines such as interleukin 1beta and tumor necrosis factor alpha initiate and propagate almost all consequences of the systemic inflammatory response syndrome. On the other hand, depletion of pancreatic glutathione is an early hallmark of acute pancreatitis and reactive oxygen species are also associated with the inflammatory process. Changes in thiol homestasis and redox signaling decisively contribute to amplification of the inflammatory cascade through mitogen activated protein kinase (MAP kinase) pathways. This review focuses on the relationship between oxidative stress, pro-inflammatory cytokines and MAP kinase/protein phosphatase pathways as major modulators of the inflammatory response in acute pancreatitis. Redox sensitive signal transduction mediated by inactivation of protein phosphatases, particularly protein tyrosin phosphatases, is highlighted.

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“…However, there is not agreement about its beneficial or detrimental role in this disease [57] ; moreover, an increase in NO has been suggested in SAP in humans [58] , but this issue is not yet clear [59] . We have demonstrated, by using an experimental model of necrotizing AP in rats, that NO and other va sodilators may exert a beneficial effect on SAP when they are administered before induction of pancreatitis [55] .…”

Section: From Local Pancreatic Damage To Systemic Effectsmentioning

confidence: 99%

Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis

García

Calvo²

2010

WJGPT

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Acute pancreatitis (AP) is a common and potentially lethal acute inflammatory process. Although the majority of patients have a mild episode of AP, 10%-20% develop a severe acute pancreatitis (SAP) and suffer systemic inflammatory response syndrome (SIRS) and/or pancreatic necrosis. The main aim of this article is to review the set of events, first localized in the pancreas, that lead to pancreatic inflammation and to the spread to other organs contributing to multiorganic shock. The early pathogenic mechanisms in SAP are not completely understood but both premature activation of enzymes inside the pancreas, related to an impaired cytosolic Ca 2+ homeostasis, as well as release of pancreatic enzymes into the bloodstream are considered important events in the onset of pancreatitis disease. Moreover, afferent fibers within the pancreas release neurotransmitters in response to tissue damage. The vasodilator effects of these neurotransmitters and the activation of pro-inflammatory substances play a crucial role in amplifying the inflammatory response, which leads to systemic manifestation of AP. Damage extension to other organs leads to SIRS, which is usually associated with cardiocirculatory physiology impairment and a hypotensive state. Hypotension is a risk factor for death and is associated with a significant hyporesponsiveness to vasoconstrictors. This indicates that stabilization of the patient, once this pathological situation has been established, would be a very difficult task. Therefore, it seems particularly necessary to understand the pathological mechanisms involved in the first phases of AP to avoid damage beyond the pancreas. Moreover, efforts must also be directed to identify those patients who are at risk of developing SAP.

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Expression of Nitric Oxide Synthase Isoforms and Nitric Oxide Production in Acute Pancreatitis and Associated Lung Injury

Cited by 30 publications

References 46 publications

Tumor necrosis factor-α induces increased lung vascular permeability: A role for GSK3α/β

Tumor necrosis factor-α induces increased lung vascular permeability: A role for GSK3α/β

Cross-Talk between Oxidative Stress and Pro-Inflammatory Cytokines in Acute Pancreatitis: A Key Role for Protein Phosphatases

Cardiocirculatory pathophysiological mechanisms in severe acute pancreatitis

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