Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates lipopolysaccharide-induced tissue factor expression in pulmonary microvasculature

Mizumura, Kenji; Gon, Yasuhiro; Kumasawa, Fumio; Onose, Akira; Maruoka, Shuichiro; Matsumoto, Ken; Hayashi, S.; Kobayashi, Tomoko; Hashimoto, Shigeo

doi:10.1016/j.intimp.2010.06.006

Cited by 20 publications

(13 citation statements)

References 33 publications

(41 reference statements)

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“…The other two subfamilies of MAPK family (ERK1/2 and JNK1/2) have been implicated in inflammatory response and apoptosis under septic conditions [31, 44]. We show that incubation with LPS for 24 h increased the levels of phosphorylated JNK1/2 but not ERK1/2 in LPS-stimulated PMECs.…”

Section: Discussionmentioning

confidence: 59%

Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling

et al. 2016

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Pulmonary microvascular endothelial cells (PMECs) injury including apoptosis plays an important role in the pathogenesis of acute lung injury during sepsis. Our recent study has demonstrated that calpain activation contributes to apoptosis in PMECs under septic conditions. This study investigated how calpain activation mediated apoptosis and whether heat stress regulated calpain activation in lipopolysaccharides (LPS)-stimulated PMECs. In cultured mouse primary PMECs, incubation with LPS (1 µg/ml, 24 h) increased active caspase-3 fragments and DNA fragmentation, indicative of apoptosis. These effects of LPS were abrogated by pre-treatment with heat stress (43 °C for 2 h). LPS also induced calpain activation and increased phosphorylation of p38 MAPK. Inhibition of calpain and p38 MAPK prevented apoptosis induced by LPS. Furthermore, inhibition of calpain blocked p38 MAPK phosphorylation in LPS-stimulated PMECs. Notably, heat stress decreased the protein levels of calpain-1/2 and calpain activities, and blocked p38 MAPK phosphorylation in response to LPS. Additionally, forced up-regulation of calpain-1 or calpain-2 sufficiently induced p38 MAPK phosphorylation and apoptosis in PMECs, both of which were inhibited by heat stress. In conclusion, heat stress prevents LPS-induced apoptosis in PMECs. This effect of heat stress is associated with down-regulation of calpain expression and activation, and subsequent blockage of p38 MAPK activation in response to LPS. Thus, blocking calpain/p38 MAPK pathway may be a novel mechanism underlying heat stress-mediated inhibition of apoptosis in LPS-stimulated endothelial cells.

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Section: Discussionmentioning

confidence: 59%

Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling

et al. 2016

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“…22) LPS-induced tissue factor (TF) expression also requires ASK1. 99) Pulmonary microvascular expression of TF is suggested to initiate the activation of the blood coagulation cascade, resulting in acute lung injury by LPS.…”

Section: Ask1 In Diseasesmentioning

confidence: 99%

Therapeutic targets in the ASK1-dependent stress signaling pathways

Hayakawa

Takeda

et al. 2012

Proceedings of the Japan Academy. Ser. B: Physical and Biologic

106

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Apoptosis signal-regulating kinase 1 (ASK1) is a member of the mitogen-activated protein kinase kinase kinase (MAP3K) family that activates downstream MAP kinases (MAPKs), c-Jun N-terminal kinases (JNKs) and p38 MAPKs, in response to various stresses, such as reactive oxygen species (ROS), endoplasmic reticulum (ER) stress, lipopolysaccharide, and calcium overload. Activation of the JNK and p38 pathways induces stress responses such as cell death, differentiation, and the production of inflammatory cytokines. A series of studies using ASK1-deficient mice have indicated that ASK1 plays important roles in many stress-related diseases, including cardiovascular and neurodegenerative diseases, suggesting that small compounds that inhibit ASK1 activity could possibly be used for the amelioration of the development and/or progression of these diseases. In this review, we provide an overview of the pathophysiological roles of ASK1-dependent signaling pathways and discuss the mechanistic basis for how these could serve as potential therapeutic targets.

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“…Hydrogen sulfide (H 2 S), which is known as a toxic gas, is endogenously generated from cysteine and homocysteine in many, if not all, tissues by two cytosolic enzymes, cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) (Mizumura et al 2010;You et al 2011). Furthermore, it has also been shown that mitochondrial, 3-mercaptopyruvate sulfurtransferase (3-MPST) plays an important role in the synthesis of sulfide (Wang 2002;Moore et al 2003;Olson 2011).…”

mentioning

confidence: 99%

Psoriasis Is Associated with Low Serum Levels of Hydrogen Sulfide, a Potential Anti-inflammatory Molecule

Alshorafa

Guo

Zeng

et al. 2012

Tohoku J. Exp. Med.

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Psoriasis, characterized by circumscribed, red, thickened plaques with an overlying silver-white scale, is a common T-cell-mediated chronic inflammatory skin disease. Although hydrogen sulfide (H 2 S) has been shown to be a signaling molecule with both pro-or anti-inflammatory effects, its relationship with psoriasis has not been elucidated. In the present study, 15 patients with chronic progressive psoriasis and 15 healthy volunteers were investigated. Serum H 2 S levels in psoriasis patients were significantly lower than those of healthy controls (16.69 ± 5.47 μM vs. 34.5 ± 6.39 μM). In contrast, serum levels of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) were significantly higher in psoriasis patients than healthy controls (22.88 ± 6.24 pg/ml vs. 12.07 ± 3.68 pg/ml; 61.47 ± 8.21 pg/ml vs. 31.54 ± 13.73 pg/ml; and 39.43 ± 8.56 pg/ml vs. 20.55 ± 6.45 pg/ml, respectively). The serum H 2 S levels negatively correlated with clinical disease severity. Furthermore, treatment of HaCaT human keratinocytes with TNF-α increased the levels of nitric oxide (NO), IL-6 and IL-8 (32.21 ± 5.71 μM vs. 3.22 ± 0.98 μM; 203.96 ± 13.16 pg/ml vs. 13.57 ± 3.75 pg/ml; and 301.24 ± 30.17 pg/ml vs. 29.06 ± 10.91 pg/ml, respectively) in the culture media. Exogenous H 2 S inhibited the TNF-α -mediated upregulation of NO, IL-6 and IL-8 in a dosedependent manner. In addition, H 2 S inhibited TNF-α-mediated activation of p38, extracellular-signalregulated kinase and nuclear factor kappa B. In conclusion, H 2 S may play a protective role in the pathogenesis of psoriasis. H 2 S-releasing agents may be promising therapeutics for psoriasis.

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Apoptosis signal-regulating kinase 1-mediated signaling pathway regulates lipopolysaccharide-induced tissue factor expression in pulmonary microvasculature

Cited by 20 publications

References 33 publications

Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling

Heat stress prevents lipopolysaccharide-induced apoptosis in pulmonary microvascular endothelial cells by blocking calpain/p38 MAPK signalling

Therapeutic targets in the ASK1-dependent stress signaling pathways

Psoriasis Is Associated with Low Serum Levels of Hydrogen Sulfide, a Potential Anti-inflammatory Molecule

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