Hyperoxia Increases Protein Mass of 5-Lipoxygenase and Its Activating Protein, Flap, and Leukotriene B 4 Output in Newborn Rat Lungs

Hosford, Gayle E.; Koyanagi, Kim Shigeko.; Leung, Wynne I.; Olson, David M.

doi:10.1080/01902140260426751

Cited by 6 publications

(3 citation statements)

References 19 publications

(16 reference statements)

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“…Most LMs are produced by the combined reactions of regio‐ and stereo‐specific LOXs determined by the oxygen migration in the protein matrix (Coffa & Brash, 2004; Mishra & Mishra, 2019, 2020; Saam et al, 2007). LOXs were discovered as 5 S ‐ (Gilbert et al, 2011; Hosford et al, 2002), 8 S / R ‐ (Gilbert et al, 2018; Okazaki et al, 2002), 11 S/R ‐ (An et al, 2018; Mortimer et al, 2006), 12 S / R ‐ (Deng et al, 2014; Horn et al, 2013; Jobard et al, 2002), and 15 S/R ‐types (Hamberg et al, 1998; Zhao et al, 2011) on ARA in animals and plants, but rarely in microorganisms.…”

Section: Introductionmentioning

confidence: 99%

Biocatalytic synthesis of dihydroxy fatty acids as lipid mediators from polyunsaturated fatty acids by double dioxygenation of the microbial 12S‐lipoxygenase

Liu

Kim

2021

Biotech & Bioengineering

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Leukotrienes (LTs) and maresins (MaRs) are human lipid mediators (LMs) involved in immune response and anti-inflammation, respectively. These compounds and their isomers are generated in trace amounts by lipoxygenases (LOXs) in human macrophages and neutrophils. These LMs have been synthesized using nonenvironmentally benign synthetic protocols, which are expensive. 8S-and 15S-LOXs with double dioxygenating activities have previously been reported, whereas 12S-LOX with double dioxygenating activity have not been reported to date. Here, we discovered a wild-type 12S-LOX with double dioxygenating activity from the bacterium Endozoicomonas numazuensis, which produced dihydroxy fatty acids (DiHFAs) as LMs from polyunsaturated fatty acids via double dioxygenation. The enzyme activity for producing DiHFA was approximately 550-fold higher than that of mammalian LOX with double dioxygenating activity. The microbial 12S-LOX converted 3.00 mM of arachidonic acid, eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid to 2.37 mM (797 mg/L) 6-trans-8-cis-12S-epimer of LTB4, 1.59 mM (532 mg/L) 6-trans-8-cis-12S-epimer of LTB5, 1.35 mM (498 mg/L) 10-cis-12-trans-7S-epimer of MaR1 n-3 DPA , and 1.54 mM (555 mg/L) 10-cis-12-trans-7Sepimer of MaR1 within 2 h, which were 5.3-, 7.6-, 3.1-, and 5.5-fold higher than those biosynthesized by the previously reported microbial engineered 12S-LOX with double dioxygenating activity, respectively. These findings contribute to the efficient and environmentally friendly biosynthesis of LMs and stimulate physiological study on LMs.

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Section: Introductionmentioning

confidence: 99%

Biocatalytic synthesis of dihydroxy fatty acids as lipid mediators from polyunsaturated fatty acids by double dioxygenation of the microbial 12S‐lipoxygenase

Liu

Kim

2021

Biotech & Bioengineering

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“…Little is known about the effect of ROI on the expression of 5-LO. Other investigators examined the effect of hyperoxia on 5-LO expression in the lungs of newborn rat lung tissue [43]. LT synthesis and total lung expression of 5-LO were increased in animals treated with hyperoxia.…”

Section: Discussionmentioning

confidence: 99%

NADPH oxidase deficiency results in reduced alveolar macrophage 5-lipoxygenase expression and decreased leukotriene synthesis

Coffey

Serezani

Phare

et al. 2007

Journal of Leukocyte Biology

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Reactive oxygen intermediates (ROI) play an important role in cell signaling in addition to their role in microbial killing. We have shown previously that exogenous ROI regulate activity of the enzyme 5-lipoxygenase (5-LO) in alveolar macrophages (AM). Here, we examined the role of endogenous ROI, specifically generated by NADPH oxidase, in the regulation of leukotriene (LT) synthetic capacity in AM, which from NADPH oxidase knockout (KO) mice, was significantly less than that from wild-type (WT) AM. The decrease in LT synthesis could not be explained by reduced release of the substrate for 5-LO, arachidonic acid. However, the expression of 5-LO was reduced approximately 50% in AM from NADPH oxidase KO mice compared with WT mice. Reduced 5-LO expression could be reproduced by treating WT AM with ROI scavengers and with selective pharmacologic inhibitors of NADPH oxidase. Furthermore, conditioned media from WT AM augmented 5-LO metabolism in AM from NADPH oxidase KO mice. This decrease in 5-LO expression in NADPH oxidase KO cells was associated with decreased expression of the transcription factors, specificity protein-1 and early growth response-1, both of which are known to regulate 5-LO mRNA expression. These data reveal a previously unrecognized influence of endogenous ROI generated by NADPH oxidase on expression of the key LT biosynthetic protein, 5-LO. In view of the antimicrobial actions of LT, a reduction in LT synthetic capacity by AM from NADPH oxidase KO mice may contribute to the susceptibility of these animals to infection.

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“…As products of cyclooxygenase and lipoxygenase, these oxylipins may result in abnormal inflammatory responses in infants who develop BPD. Indeed, hyperoxia increased the activity and levels of cyclooxygenase and lipoxygenase in newborn rat lungs, and deficiency of cyclooxygenase 2 attenuated hyperoxia-induced lung inflammatory responses [ 82 , 83 ]. Therefore, reducing lipid peroxidation and oxylipins could be a potential therapy to prevent or mitigate the development of BPD.…”

Section: Dysregulated Lipid Metabolism In Bpdmentioning

confidence: 99%

Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches

Dennery

et al. 2021

Redox Biology

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Bronchopulmonary dysplasia (BPD) is a common chronic lung disease in premature infants. Accumulating evidence shows that dysregulated metabolism of glucose, lipids and amino acids are observed in premature infants. Animal and cell studies demonstrate that abnormal metabolism of these substrates results in apoptosis, inflammation, reduced migration, abnormal proliferation or senescence in response to hyperoxic exposure, and that rectifying metabolic dysfunction attenuates neonatal hyperoxia-induced alveolar simplification and vascular dysgenesis in the lung. BPD is often associated with several comorbidities, including pulmonary hypertension and neurodevelopmental abnormalities, which significantly increase the morbidity and mortality of this disease. Here, we discuss recent progress on dysregulated metabolism of glucose, lipids and amino acids in premature infants with BPD and in related in vivo and in vitro models. These findings suggest that metabolic dysregulation may serve as a biomarker of BPD and plays important roles in the pathogenesis of this disease. We also highlight that targeting metabolic pathways could be employed in the prevention and treatment of BPD.

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Hyperoxia Increases Protein Mass of 5-Lipoxygenase and Its Activating Protein, Flap, and Leukotriene B 4 Output in Newborn Rat Lungs

Cited by 6 publications

References 19 publications

Biocatalytic synthesis of dihydroxy fatty acids as lipid mediators from polyunsaturated fatty acids by double dioxygenation of the microbial 12S‐lipoxygenase

Biocatalytic synthesis of dihydroxy fatty acids as lipid mediators from polyunsaturated fatty acids by double dioxygenation of the microbial 12S‐lipoxygenase

NADPH oxidase deficiency results in reduced alveolar macrophage 5-lipoxygenase expression and decreased leukotriene synthesis

Metabolic dysregulation in bronchopulmonary dysplasia: Implications for identification of biomarkers and therapeutic approaches

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