Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection

Loke, Wai Mun; Chow, Angelia; Sing, Karen Lam Mok; Lee, Jetty Chung‐Yung; Halliwell, Barry; Lim, Erle C.H.; Quek, Amy M.L.; Ooi, Eng Eong; Seet, Raymond C.S.

doi:10.1186/1743-422x-10-322

Cited by 14 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…reported that in rat aortic vascular smooth muscle cells, angiotensin II involves 5‐LOX to produce leukotriene B 4 from arachidonic acid 2.5 min after treatment; whereas, inhibition of 5‐LOX by MK886 attenuates angiotensin II‐induced leukotriene B 4 production, suggesting that 5‐LOX is involved early in the production of leukotriene B 4. In contrast, exposure of human neutrophils to dengue virus induces 5‐LOX expression 7 h after exposure to dengue virus, and augments leukotriene B 4 production . In our current study, dexmedetomidine‐induced contraction involving 5‐LOX was rather acute; 5‐LOX and COX‐2 expression was upregulated at 10–60 min and 10–20 min after pretreatment with dexmedetomidine, respectively.…”

Section: Discussioncontrasting

confidence: 50%

Dexmedetomidine-induced contraction involves c-JunNH₂-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta

Byon

Jin

et al. 2014

Clin Exp Pharmacol Physiol

View full text Add to dashboard Cite

Vasoconstriction induced by dexmedetomidine, a highly selective alpha-2 adrenoceptor agonist, mainly involves c-Jun NH2 -terminal kinase (JNK) phosphorylation in the isolated endothelium-denuded aorta. We carried out an in vitro study to determine the main arachidonic acid metabolic pathway that is involved in dexmedetomidine-induced JNK activation. Cumulative dexmedetomidine concentration-contractile response curves were generated in the endothelium-denuded rat aorta in the presence or absence of the following inhibitors: the JNK inhibitor SP600125, the phospholipase A2 inhibitor quinacrine dihydrochloride, the non-specific lipoxygenase (LOX) inhibitor nordihydroguaiaretic acid, the 5-LOX inhibitor AA-861, the dual 5-LOX and cyclooxygenase (COX) inhibitor phenidone, the non-specific COX inhibitor indomethacin, the cytochrome p450 epoxygenase inhibitor fluconazole, the COX-1 inhibitor SC-560, and the COX-2 inhibitor NS-398. The effect of the alpha-2 adrenoceptor inhibitor rauwolscine and other inhibitors, such as quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, indomethacin and the protein kinase C inhibitor GF 109203X, on dexmedetomidine-induced JNK phosphorylation was investigated in rat aortic vascular smooth muscle cells with western blotting. The effect of dexmedetomidine on 5-LOX and COX-2 expression was investigated in vascular smooth muscle cells. SP600125, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone, rauwolscine and chelerythrine attenuated dexmedetomidine-induced contraction. Indomethacin slightly attenuated dexmedetomidine-induced contraction. Fluconazole and SC-560 had no effect on dexmedetomidine-induced contraction, whereas NS-398 attenuated contraction. SP600125, rauwolscine, quinacrine dihydrochloride, nordihydroguaiaretic acid, AA-861, phenidone and GF 109203X attenuated dexmedetomidine-induced JNK phosphorylation. 5-LOX and COX-2 were upregulated by dexmedetomidine. Thus, dexmedetomidine-induced alpha-2 adrenoceptor-mediated contraction is mediated mainly by 5-LOX and partially by COX-2, which leads to JNK phosphorylation.

show abstract

Section: Discussioncontrasting

confidence: 50%

Dexmedetomidine-induced contraction involves c-JunNH₂-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta

Byon

Jin

et al. 2014

Clin Exp Pharmacol Physiol

View full text Add to dashboard Cite

show abstract

“…In the presence of MK886 ( ALOX5 activating protein antagonist) the increase in leukotriene B4 biosynthesis is reduced indicating the relevance of the ALOX5 pathway in dengue virus infection. Consistent with this conclusion is the observation that in vivo plasma levels of leukotriene B4 were significantly elevated during the febrile stages of dengue infections [389]. …”

Section: Lipoxygenase Isoforms In Infectious Diseasessupporting

confidence: 55%

“…When human neutrophils are infected in vitro with the dengue virus (DENV-2), ALOX5 expression is upregulated and the cells biosynthesize significantly more leukotriene B4 [389]. In the presence of MK886 ( ALOX5 activating protein antagonist) the increase in leukotriene B4 biosynthesis is reduced indicating the relevance of the ALOX5 pathway in dengue virus infection.…”

Section: Lipoxygenase Isoforms In Infectious Diseasesmentioning

confidence: 99%

Mammalian lipoxygenases and their biological relevance

Kühn

Banthiya

Leyen

2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biolog

480

431

View full text Add to dashboard Cite

Lipoxygenases (LOXs) form a heterogeneous class of lipid peroxidizing enzymes, which have been implicated in cell proliferation and differentiation but also in the pathogenesis of various diseases with major public health relevance. As other fatty acid dioxygenases LOX oxidize polyunsaturated fatty acids to their corresponding hydroperoxy derivatives, which are further transformed to bioactive lipid mediators (eicosanoids and related substances). On the other hand, lipoxygenases are key players in regulation of the cellular redox homeostasis, which is an important element in gene expression regulation. Although the first mammalian lipoxygenases were discovered 40 years ago and although the enzymes have been well characterized with respect to their structural and functional properties the biological roles of the different lipoxygenase isoforms are not completely understood. This review is aimed at summarizing the current knowledge on the physiological roles of different mammalian LOX-isoforms and their patho-physiological function in inflammatory, metabolic, hyperproliferative, neurodegenerative and infectious disorders.

show abstract

“…Apart from being pro‐inflammatory mediators and potent chemoattractants, some are also known to increase vascular permeability and induce vascular leak . Increased activity of LTB4 has been observed in patients with acute dengue viral infection, and exposure of neutrophils to the DENV induced the production of LTB4 . In addition, in experimental dengue mouse models, treatment with leukotriene receptor antagonists resulted in a significant reduction in plasma leakage in dengue‐infected mice, suggesting that leukotrienes may be playing an important role in fluid leakage in dengue.…”

Section: Introductionmentioning

confidence: 99%

Pathogenesis of vascular leak in dengue virus infection

2017

View full text Add to dashboard Cite

SummaryEndothelial dysfunction leading to vascular leak is the hallmark of severe dengue. Vascular leak typically becomes clinically evident 3-6 days after the onset of illness, which is known as the critical phase. This critical phase follows the period of peak viraemia, and lasts for 24-48 hr and usually shows rapid and complete reversal, suggesting that it is likely to occur as a result of inflammatory mediators, rather than infection of the endothelium. Cytokines such as tumour necrosis factor-a, which are known to be elevated in the critical phase of dengue, are likely to be contributing factors. Dengue NS1, a soluble viral protein, has also been shown to disrupt the endothelial glycocalyx and thus contribute to vascular leak, although there appears to be a discordance between the timing of NS1 antigenaemia and occurrence of vascular leak. In addition, many inflammatory lipid mediators are elevated in acute dengue viral infection such as platelet activating factor (PAF) and leukotrienes. Furthermore, many other inflammatory mediators such as vascular endothelial growth factor and angiopoietin-2 have been shown to be elevated in patients with dengue haemorrhagic fever, exerting their action in part by inducing the activity of phospholipases, which have diverse inflammatory effects including generation of PAF. Platelets have also been shown to significantly contribute to endothelial dysfunction by production of interleukin-1b through activation of the NLRP3 inflammasome and also by inducing production of inflammatory cytokines by monocytes. Drugs that block down-stream immunological mediator pathways such as PAF may also be beneficial in the treatment of severe disease.

show abstract

Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection

Cited by 14 publications

References 38 publications

Dexmedetomidine-induced contraction involves c-JunNH₂-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta

Dexmedetomidine-induced contraction involves c-JunNH₂-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta

Mammalian lipoxygenases and their biological relevance

Pathogenesis of vascular leak in dengue virus infection

Contact Info

Product

Resources

About

Augmentation of 5-lipoxygenase activity and expression during dengue serotype-2 infection

Cited by 14 publications

References 38 publications

Dexmedetomidine-induced contraction involves c-JunNH2-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta

Dexmedetomidine-induced contraction involves c-JunNH2-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta

Mammalian lipoxygenases and their biological relevance

Pathogenesis of vascular leak in dengue virus infection

Contact Info

Product

Resources

About

Dexmedetomidine-induced contraction involves c-JunNH₂-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta

Dexmedetomidine-induced contraction involves c-JunNH₂-terminal kinase phosphorylation through activation of the 5-lipoxygenase pathway in the isolated endothelium-denuded rat aorta