Phorbol Myristate Acetate Induces Neutrophil Death through Activation of p38 Mitogen-Activated Protein Kinase That Requires Endogenous Reactive Oxygen Species Other Than HOCl

Saito, Takao; Takahashi, Hajime; Doken, Hideo; Koyama, Hideki; Aratani, Yasuaki

doi:10.1271/bbb.69.2207

Cited by 17 publications

(14 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To the contrary, the proapoptotic influence of exogenous ROS, in particular the superoxide radical, was found by Saito et al (2005) in murine neutrophils deprived of NADPH oxidase, however, the authors did not link this effect to caspase-dependent cell death but to the p38 MAP-kinase pathway. Moreover, both apoptotic pathways, caspase 3-dependent and p38 MAPKdependent were involved in human polymorphonuclear neutrophils exposed to curcumin, a spice with a polyphenol structure and a known COX-2 inhibitor (Hu et al, 2005).…”

Section: Resultsmentioning

confidence: 90%

Citrus fruit flavonoids influence on neutrophil apoptosis and oxidative metabolism

Zielińska-Przyjemska

Ignatowicz

2008

Phytotherapy Research

View full text Add to dashboard Cite

Citrus flavonoids are dietary antioxidants that may protect against oxidative stress linked to inflammation and reduce the risk of macromolecule damage caused by free radicals. Three citrus flavonoids - naringin, naringenin and hesperidin - have been examined for their ability to activate caspase-3, a marker of apoptosis execution, in human polymorphonuclear neutrophils in vitro, stimulated and non-stimulated with phorbol 12-myristate 13-acetate. The flavonoid potency to reduce reactive oxygen species generation was also assessed in measurements of superoxide radical and luminol dependent chemiluminescence. The caspase-3 activity depended on the time of flavonoid treatment and was increased markedly in phorbol-treated cells incubated with flavonoids for 24 h. Hesperidin at a concentration of 100 microm exerted the strongest stimulating effect on the enzyme (137% of control). Flavonoids inhibited the neutrophil ability to generate superoxide radical and 10-100 microM hesperidin appeared the most active phytochemical. The antioxidant capacity of the examined flavonoids was most prominently expressed in the chemiluminescent measurements. The obtained results suggest that reactive oxygen species may inhibit apoptosis via caspase-3 inhibition and the antioxidant action of citrus flavonoids may reverse this process.

show abstract

Section: Resultsmentioning

confidence: 90%

Citrus fruit flavonoids influence on neutrophil apoptosis and oxidative metabolism

Zielińska-Przyjemska

Ignatowicz

2008

Phytotherapy Research

View full text Add to dashboard Cite

show abstract

“…1), suggesting that, in addition to the up-regulation of MIP-2 production at 6 h post-zymosan treatment, additional underlying mechanisms contribute to the enhanced lung inflammation in the mutant mice. We previously reported that apoptosis in MPO-deficient neutrophils stimulated by phorbol myristate acetate was significantly slower than in normal neutrophils [28,29]. Therefore, as a possible mechanism, retardation of neutrophil apoptosis due to MPO deficiency causes an increase in neutrophil numbers in the zymosan-exposed lungs of MPO -/-mice.…”

Section: Discussionmentioning

confidence: 99%

Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan

et al. 2011

Self Cite

View full text Add to dashboard Cite

show abstract

“…9). Of interest, there are a number of reports that have implicated p38 in necroptotic-like death processes (95,96), and the necroptosis-inducing receptor-interacting protein has been shown to activate p38 (97).…”

Section: Discussionmentioning

confidence: 99%

Sitosterol-containing Lipoproteins Trigger Free Sterol-induced Caspase-independent Death in ACAT-competent Macrophages

Bao

Deng

et al. 2006

Journal of Biological Chemistry

View full text Add to dashboard Cite

Sitosterolemia is a disease characterized by very high levels of sitosterol and other plant sterols and premature atherothrombotic vascular disease. One theory holds that plant sterols can directly promote atherosclerosis, but the mechanism is not known. Unesterified, or "free," cholesterol (FC) is a potent inducer of macrophage death, which causes plaque necrosis, a precursor to atherothrombosis. FC-induced macrophage death, however, requires dysfunction of the sterol esterifying enzyme acyl-coenzyme A-cholesterol acyltransferase (ACAT), which likely occurs slowly during lesion progression. In contrast, plant sterols are relatively poorly esterified by ACAT, and so they may cause macrophage death and plaque necrosis in an accelerated manner. In support of this hypothesis, we show here that macrophages incubated with sitosterol-containing lipoproteins accumulate free sterols and undergo death in the absence of an ACAT inhibitor. As with FC loading, sitosterol-induced macrophage death requires sterol trafficking to the endoplasmic reticulum, and sitosterol-enriched endoplasmic reticulum membranes show evidence of membrane protein dysfunction. However, whereas FC induces caspase-dependent apoptosis through activation of the unfolded protein response and JNK, sitosterol-induced death is caspase-independent and involves neither the unfolded protein response nor JNK. Rather, cell death shows signs of necroptosis and autophagy and is suppressed by inhibitors of both processes. These data establish two new concepts. First, a relatively subtle change in sterol structure fundamentally alters the type of death program triggered in macrophages. Understanding the basis of this alteration should provide new insights into the molecular basis of death pathway signaling. Second, sitosterol-induced macrophage death does not require ACAT dysfunction and so may occur in an accelerated fashion. Pending future in vivo studies, this concept may provide at least one mechanism for accelerated plaque necrosis and atherothrombotic disease in patients with sitosterolemia.

show abstract

Phorbol Myristate Acetate Induces Neutrophil Death through Activation of p38 Mitogen-Activated Protein Kinase That Requires Endogenous Reactive Oxygen Species Other Than HOCl

Cited by 17 publications

References 28 publications

Citrus fruit flavonoids influence on neutrophil apoptosis and oxidative metabolism

Citrus fruit flavonoids influence on neutrophil apoptosis and oxidative metabolism

Severe neutrophil-mediated lung inflammation in myeloperoxidase-deficient mice exposed to zymosan

Sitosterol-containing Lipoproteins Trigger Free Sterol-induced Caspase-independent Death in ACAT-competent Macrophages

Contact Info

Product

Resources

About