Lysophosphatidylcholine suppresses apoptosis and induces neurite outgrowth in PC12 cells through activation of phospholipase D2

Yun, Doo Hee; Jeon, Eun-Ju; Sung, Sang-Min; Ryu, Sung Ho; Kim, Jae Ho

doi:10.1038/emm.2006.44

Cited by 20 publications

(8 citation statements)

References 40 publications

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“…It activates multiple molecular targets, including six G protein-coupled receptors, which in turn stimulate various signaling pathways 63,64 . In the present study, we identified that LPC, but not LPA, promoted morphological change in vitro, consistent with a previous report which demonstrated that LPC induces morphological change in PC12 cells by activating phospholipase D 2 65 . Interestingly, the ATX inhibitor BI-2545 also significantly promoted morphological change in BV-2 and SIM-A9 cells, which suggests that LPC may promote morphological change by inhibiting ATX.…”

Section: Discussionsupporting

confidence: 93%

Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro

Tsukahara

Haniu

Uemura

et al. 2020

Sci Rep

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cognitive impairments such as dementia are common in later life, and have been suggested to occur via a range of mechanisms, including oxidative stress, age-related changes to cellular metabolism, and a loss of phospholipids (pLs) from neuronal membranes. pLs are a class of amphipathic lipids that form plasma membrane lipid bilayers, and that occur at high concentrations in neuronal membranes. our previous study suggested that a porcine liver decomposition product (pLDp) produced via protease treatment may improve cognitive function at older ages, by acting as a rich source of pLs and lysophospholipids (LPLs); however, its specific composition remains unclear. Thus, the present study used a novel liquid chromatography electrospray ionization tandem mass spectrometric (Lc-MS/MS) protocol to identify the major PLs and LPLs in PLDP. Furthermore, it assessed the effect of identified LPLs on microglial activation in vitro, including cell shape, proliferation, and cell morphology. the results of the conducted analyses showed that pLDp and pLDp-derived LpLs concentrationdependently modulate microglial activation in vitro. in particular, lysophosphatidylcholine (Lpc) concentration-dependently promotes cell morphology, likely via effects mediated by the enzyme autotaxin (AtX), since inhibiting AtX also promoted cell morphology, while conversely, increasing AtX production (via treatment with high levels of LPC) abolished this effect. These findings suggest that Lpc is likely neuroprotective, and thus, support the importance of further research to assess its use as a therapeutic target to treat age-related cognitive impairments, including dementia.Rapid population aging and age-related disease represent an increasing global health-care burden. Dementias are the most common cause of significant late-onset cognitive decline, and affect approximately 50 million people worldwide, with nearly 10 million new cases diagnosed annually 1 . There are many different forms of dementia; for example, Alzheimer's disease is the most common form, and contributes to 60-70% of cases. Other major forms include vascular and Lewy body dementia, and a group of diseases that together comprise frontotemporal dementia 2 . Patients with mild cognitive impairment (MCI) are at risk of developing dementia; however, in some individuals, MCI reverts to normal cognition or remains stable. While clinical studies are currently being conducted to identify novel treatments to improve symptoms and/or prevent or delay the progression of MCI to dementia, no drugs or other treatments have yet been specifically approved for MCI. Lipids are increasingly recognized for their roles in neuronal function in the brain 3,4 ; for example, the lipid fraction of mammalian membranes consists of glycerophospholipids, sphingolipids, and cholesterol 4 . We previously reported that a porcine liver decomposition product (PLDP) induces a significant increase in the Hasegawa's Dementia Scale-Revised (HDS-R) score in a randomized, double-blind, placebo-controlled study in healthy hu...

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Section: Discussionsupporting

confidence: 93%

Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro

Tsukahara

Haniu

Uemura

et al. 2020

Sci Rep

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“…2004). Furthermore, a recent study showed that lysophosphatidylcholine promotes neurotrophic effects, such as anti‐apoptosis and neurite outgrowth, through activation of PLD2 (Yun et al. 2006).…”

Section: Discussionmentioning

confidence: 99%

“…2001; Watanabe et al. 2004) and PLD2 enhances lysophosphatidylcholine‐induced neurite outgrowth (Yun et al. 2006).…”

mentioning

confidence: 99%

Depolarization‐induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway

Banno

Nemoto

Murakami

et al. 2007

Journal of Neurochemistry

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The present study examined the role of phospholipase D2 (PLD2) in the regulation of depolarization-induced neurite outgrowth and the expression of growth-associated protein-43 (GAP-43) and synapsin I in rat pheochromocytoma (PC12) cells. Depolarization of PC12 cells with 50 mmol/L KCl increased neurite outgrowth and elevated mRNA and protein expression of GAP-43 and synapsin I. These increases were suppressed by inhibition of Ca 2+ -calmodulin-dependent protein kinase II (CaMKII), PLD, or mitogen-activated protein kinase kinase (MEK). Knockdown of PLD2 by small interfering RNA (siRNA) suppressed the depolarization-induced neurite outgrowth, and the increase in GAP-43 and synapsin I expression. Depolarization evoked a Ca 2+ rise that activated various signaling enzymes and the cAMP response element-binding protein (CREB). Silencing CaMKIId by siRNA blocked KCl-induced phosphorylation of proline-rich protein tyrosine kinase 2 (Pyk2), Src kinase, and extracellular signal-regulated kinase (ERK). Inhibition of Src or MEK abolished phosphorylation of ERK and CREB. Furthermore, phosphorylation of Pyk2, ERK, and CREB was suppressed by the PLD inhibitor, 1-butanol and transfection of PLD2 siRNA, whereas it was enhanced by overexpression of wild-type PLD2. Depolarization-induced PLD2 activation was suppressed by CaMKII and Src inhibitors, but not by MEK or protein kinase A inhibitors. These results suggest that the signaling pathway of depolarization-induced PLD2 activation was downstream of CaMKIId and Src, and upstream of Pyk2(Y881) and ERK/CREB, but independent of the protein kinase A. This is the first demonstration that PLD2 activation is involved in GAP-43 and synapsin I expression during depolarization-induced neuronal differentiation in PC12 cells.

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“…In vivo experiments showed that supplementation of exogenous LPCs could reduce mortality of shock rats and lessen organ damage . The hydrolysis of LPCs has two pathways: one is catalysed by phospholipase D (PLD) to generate PA, and PA can be further metabolized to diacylglycerol and LPA ; in the other pathway, lysophosphatidylcholine is directly converted into LPAs with the action of autotaxin (ATX), which possesses the function of PLD . As phospholipid molecules, LPAs possess diverse biological functions .…”

Section: Discussionmentioning

confidence: 99%

Cross‐sectional and dynamic change of serum metabolite profiling for Hepatitis B‐related acute‐on‐chronic liver failure by UPLC/MS

Nie

Han

Zhang

et al. 2013

Journal of Viral Hepatitis

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Summary Acute-on-chronic liver failure(ACLF) is an increasingly recognized entity encompassing an acute deterioration of liver function and results in the failure of one or more organs with high short-term mortality. The focus of this study was to discover noninvasive and reliable biomarkers for the diagnosis and prognosis of hepatitis B-related ACLF. Ultra-performance liquid chromatography-mass spectrometry (UPLC/MS) was used to analyse serum metabolites of 28 patients with hepatitis B-related ACLF, 35 patients with Child-Pugh A cirrhosis, 30 patients with chronic hepatitis B and 35 healthy volunteers (HS). Characteristic metabolites were screened, identified and dynamically tracked to investigate their value for diagnosis and prognosis. After comparing serum metabolic profile of hepatitis B-related ACLF and Child-Pugh A cirrhosis, 99 characteristic metabolites were selected, and 38 of them were identified. Dynamic tracking model demonstrated that 17 metabolites were related to prognosis of hepatitis B-related ACLF, and there were also 11 metabolites which improved with treatment in the survival group. The correlations between these characteristic metabolites and the model for end-stage liver disease score were strong. These observations contributed to the investigation of the mechanisms of hepatitis B-related ACLF manifestation and progression on the metabolic level, and they provided information for the identification of biomarkers for the diagnosis and prognosis of hepatitis B-related ACLF.

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Lysophosphatidylcholine suppresses apoptosis and induces neurite outgrowth in PC12 cells through activation of phospholipase D2

Abstract: Lysophosphatidylcholine (LPC) is a bioactive lipid generated by phospholipase A2-mediated hydrolysis of phosphatidylcholine. In the present study, we demonstrate that LPC stimulates phospholipase D2 (PLD2) activity in rat pheochromocytoma PC12 cells.

Cited by 20 publications

References 40 publications

Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro

Porcine liver decomposition product-derived lysophospholipids promote microglial activation in vitro

Depolarization‐induced differentiation of PC12 cells is mediated by phospholipase D2 through the transcription factor CREB pathway

Cross‐sectional and dynamic change of serum metabolite profiling for Hepatitis B‐related acute‐on‐chronic liver failure by UPLC/MS

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