Molecular mechanisms of fMLP-induced superoxide generation and degranulation in mouse neutrophils

Kanaho, Yasunori; Sato, Takanobu; Hongu, Tsunaki; Funakoshi, Yuji

doi:10.1016/j.jbior.2012.09.001

Cited by 10 publications

(3 citation statements)

References 59 publications

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“…Indeed, inhibition of EGF-stimulated PITPnm1 redistribution to the plasma membrane was observed. However, use of primary alcohols as inhibitors of PLD-mediated PtdOH production is not a rigorous approach (262)(263)(264)(265)(266). With the availability of isoformspecific PLD inhibitors, the issue can now be revisited in a more rigorous way (267)(268)(269)(270).…”

Section: Class II Pitps and Receptor Tyrosine Kinase Signaling: The Cmentioning

confidence: 99%

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

Grabon

Bankaitis

McDermott

2019

Journal of Lipid Research

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P 3 ]. Yeasts (Saccharomyces) synthesize all of these except PtdIns(3,4)P 2 and PtdIns(3,4,5)P 3. This cohort of molecules is produced by a series of reversible phosphorylation and dephosphorylation reactions catalyzed by phosphoinositide kinases (PIKs) and phosphatases, respectively, that target the inositol headgroup at positions C3, C4, and C5 (1, 2). These chemically distinct lipids, although small in number, control an impressively large set of intracellular activities. How is such diversification of biological function achieved? Current views for how PtdIns and phosphoinositide signaling are diversified focus on regulatory mechanisms that include: the regulation and localization of the enzymes that produce, degrade, or sequester phosphoinositides; the identities of the effector proteins that recognize these Abstract Phosphoinositides are key regulators of a large number of diverse cellular processes that include membrane trafficking, plasma membrane receptor signaling, cell proliferation, and transcription. How a small number of chemically distinct phosphoinositide signals are functionally amplified to exert specific control over such a diverse set of biological outcomes remains incompletely understood. To this end, a novel mechanism is now taking shape, and it involves phosphatidylinositol (PtdIns) transfer proteins (PITPs). The concept that PITPs exert instructive regulation of PtdIns 4-OH kinase activities and thereby channel phosphoinositide production to specific biological outcomes, identifies PITPs as central factors in the diversification of phosphoinositide signaling. There are two evolutionarily distinct families of PITPs: the Sec14-like and the StAR-related lipid transfer domain (START)-like families. Of these two families, the START-like PITPs are the least understood. Herein, we review recent insights into the biochemical, cellular, and physiological function of both PITP families with greater emphasis on the START-like PITPs, and we discuss the underlying mechanisms through which these proteins regulate phosphoinositide signaling and how these actions translate to human health and disease.-Grabon, A., V. A. Bankaitis, and M. I. McDermott. The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes.

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Section: Class II Pitps and Receptor Tyrosine Kinase Signaling: The Cmentioning

confidence: 99%

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

Grabon

Bankaitis

McDermott

2019

Journal of Lipid Research

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“…Awareness of problems with this method grew over the past decade, though, with the observation that the amounts of alcohol required to substantially block PA production by PLD caused substantial cellular toxicity, whereas the lower amounts used in most studies were only modestly affecting PA generation [22, 23]. With the introduction of RNAi (2003) and then small molecule inhibitors (2009), discrepancies between the different inhibitory approaches began to be noted, and a final, definitive report was presented by Kanaho and colleagues in 2013 [24]: By this time, more than 100 articles had been published on the topic of a requisite role for PLD in fMLP peptide signaling-activated superoxide production and degranulation in neutrophils, most if not all based on the use of primary alcohols to block PLD-mediated production of PA [25]. Unexpectedly, however, Sato et al [24] found that neither pharmacological inhibition of PLD1/2 using the modern small molecule inhibitor FIPI nor genetic deletion of both PLD1 and PLD2 had any effect on superoxide production and degranulation or even PA production; rather, the PA observed with fMLP stimulation was generated by DGK phosphorylation of DAG that in turn had been generated though activation of Phospholipase C (PLC).…”

Section: Pld1 and Pld2 The Signaling-activated Enzymesmentioning

confidence: 99%

The phospholipase D superfamily as therapeutic targets

Frohman

2015

Trends in Pharmacological Sciences

173

177

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The Phospholipase D (PLD) lipid-signaling enzyme superfamily has long been studied for its roles in cell communication and a wide range of cell biological processes. With the advent of loss-of-function genetic mouse models that have revealed that PLD1 and PLD2 ablation is overtly tolerable, small molecule PLD1/2 inhibitors that do not cause unacceptable clinical toxicity, a PLD2 polymorphism that has been linked to altered physiology, and growing delineation of processes subtly altered in mice lacking PLD1/2 activity, the stage is being set for assessment of PLD1/2 inhibition for therapeutic purposes. Based on findings to date, PLD1/2 inhibition may be of more utility in acute rather than chronic settings, although this generalization will depend on the specific risks and benefits in each disease setting.

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“…Так, в ряде исследований было показано, что PLD необходима для образования нейтрофилами супероксидного анион-радикала при их стимуляции бактериальным трипептидом fMLP (N-formylmethionyl-leucyl-phenylalanin) и для дегрануляции нейтрофилов, в то время как ингибирование PLD при помощи этанола или н-бутанола подавляло данные процессы [45][46][47]. Однако в 2013 году в нескольких исследованиях [48,49] было доказано, что фармакологическое ингибирование PLD1 и PLD2 при помощи FIPI и нокаут генов PLD1 и PLD2 у мышей PLD -/не влияют на образование супероксида и дегрануляцию нейтрофилов в присутствии fMLP. Следовательно, именно спирты, а не ингибированные PLD влияли на функции нейтрофилов.…”

Section: ингибиторы активности Pldunclassified

Phospholipase D: its role in metabolism processes and disease development

2018

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Phospholipase D (PLD) is one of the key enzymes that catalyzes the hydrolysis of cell membrane phospholipids. In this review current knowledge about six human PLD isoforms, their structure and role in physiological and pathological processes is summarized. Comparative analysis of PLD isoforms structure is presented. The mechanism of the hydrolysis and transphosphatidylation performed by PLD is described. The PLD1 and PLD2 role in the pathogenesis of some cancer, infectious, thrombotic and neurodegenerative diseases is analyzed. The prospects of PLD isoform-selective inhibitors development are shown in the context of the clinical usage and the already-existing inhibitors are characterized. Moreover, the formation of phosphatidylethanol (PEth), the alcohol abuse biomarker, as the result of PLD-catalyzed phospholipid transphosphatidylation is considered.

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Molecular mechanisms of fMLP-induced superoxide generation and degranulation in mouse neutrophils

Cited by 10 publications

References 59 publications

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

The interface between phosphatidylinositol transfer protein function and phosphoinositide signaling in higher eukaryotes

The phospholipase D superfamily as therapeutic targets

Phospholipase D: its role in metabolism processes and disease development

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