Release of lysophospholipid ‘find-me’ signals during apoptosis requires the ATP-binding cassette transporter A1

Peter, Christoph; Waibel, Michaela; Keppeler, Hildegard; Lehmann, Rainer; Xu, Guowang; Halama, Anna; Adamski, Jerzy; Schulze‐Osthoff, Klaus; Wesselborg, Sebastian; Lauber, Kirsten

doi:10.3109/08916934.2012.719947

Cited by 47 publications

(36 citation statements)

References 21 publications

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“…Furthermore, our results demonstrate that pretreatment with the AMPK inhibitor compound C or a specific siRNA approach to knock down AMPK expression diminished the migration of macrophages toward lyso-PC find me signaling. Although lyso-PC is a naturally occurring bioactive lipid molecule thought to be important in the pathophysiology of atherosclerosis (48,49), lyso-PC is also produced and released from dying cells (50,51). In particular, during apoptosis, the calcium-independent phospholipase A2 (iPLA2) is activated and, in turn, hydrolyzes phosphatidylcholine to lyso-PC, which is subsequently externalized and released (51).…”

Section: Discussionmentioning

confidence: 99%

Mitochondria and AMP-activated Protein Kinase-dependent Mechanism of Efferocytosis

Jiang¹,

Park

Stigler³

et al. 2013

Journal of Biological Chemistry

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Background: Billions of cells undergo apoptosis in the human body every day, and the removal of dying cells (efferocytosis) is essential for tissue homeostasis. Results: Energy demand during efferocytosis results in AMPK activation followed by enhancement of macrophage chemokinesis and efferocytosis. Conclusion: The AMPK pathway is intimately linked to cellular bioenergetics and efferocytosis. Significance: A novel mechanism of mitochondria and AMPK-dependent stimulation of efferocytosis is proposed.

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Section: Discussionmentioning

confidence: 99%

Mitochondria and AMP-activated Protein Kinase-dependent Mechanism of Efferocytosis

Jiang¹,

Park

Stigler³

et al. 2013

Journal of Biological Chemistry

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“…It might be speculated that suppression of PGE 2 or other COX/ LO-derived metabolite ( 278 ) generation can prevent the spread of ␤ -cell apoptosis. Further, lysolipids and eicosanoids act as "chemoattractants" ( 230,(279)(280)(281), and increased generation of these could promote migration of immune cells toward the islet and subsequent infi ltration, raising the possibility that in vivo inhibition of iPLA 2 ␤ could mitigate immune responses leading to T1D. Autoimmune insulitis is marked by degradation of the islet basement membrane, which presents a physical barrier to infi ltrating leukocytes ( 282 ).…”

Section: Ipla 2 ␤ and Diseasesmentioning

confidence: 99%

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Ramanadham

Ali

Ashley

et al. 2015

Journal of Lipid Research

158

170

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The Ca 2+ -independent phospholipases A 2 (iPLA 2 s) are part of a diverse family of PLA 2 s that hydrolyze the sn -2 substituent from membrane phospholipids to release a free fatty acid and a lysolipid ( 1, 2 ). These enzymes are ubiquitously expressed, and in contrast to secretory PLA 2 s (sPLA 2 s) and cytosolic PLA 2 s (cPLA 2 s), do not require Ca 2+ for either translocation or activity. Some of the fi rst descriptions of iPLA 2 activity were in the mid-to late-1980s with the identifi cation of a plasmalogen-selective PLA 2 in Abstract Among the family of phospholipases A 2 (PLA 2 s) are the Ca 2+ -independent PLA 2 s (iPLA 2 s) and they are designated group VI iPLA 2 s. In relation to secretory and cytosolic PLA 2 s, the iPLA 2 s are more recently described and details of their expression and roles in biological functions are rapidly emerging. The iPLA 2 s or patatin-like phospholipases (PNPLAs) are intracellular enzymes that do not require Ca 2+ for activity, and contain lipase (GXSXG) and nucleotide-binding (GXGXXG) consensus sequences. Though nine PNPLAs have been recognized, PNPLA8 (membraneassociated iPLA 2 ␥ ) and PNPLA9 (cytosol-associated iPLA 2 ␤ ) are the most widely studied and understood. The iPLA 2 s manifest a variety of activities in addition to phospholipase, are ubiquitously expressed, and participate in a multitude of biological processes, including fat catabolism, cell differentiation, maintenance of mitochondrial integrity, phospholipid remodeling, cell proliferation, signal transduction, and cell death. As might be expected, increased or decreased expression of iPLA 2 s can have profound effects on the metabolic state, CNS function, cardiovascular performance, and cell survival; therefore, dysregulation of iPLA 2 s can be a critical factor in the development of many diseases. This review is aimed at providing a general framework of the current understanding of the iPLA 2 s and discussion of the potential mechanisms of action of the iPLA 2 s and related involved lipid mediators. -Ramanadham, S

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“…The following oligonucleotides were used: MFG-E8 nt63: 5 0 -CGUCGCCCUGGAUAUCUGUUC CAAA-3 0 , scramble: 5 0 -CGUUCCCUAGGUCUACUUGCGCAAA-3 0 . Electroporation of 5 Â 10 6 THP-1 cells with 2 mM siRNA oligo in 500 ml OptiMEM (Invitrogen) was performed as described 45,46 At 24 h before PKH67 staining and PMA-induced differentiation into macrophages, electroporation of 5 Â 10 6 primary monocytes with 2 mM siRNA oligo in 500 ml OptiMEM (Invitrogen) was performed as described 45,46 on d0, d1 and d4 after preparation before PKH67 staining and differentiation with 20 ng/ml M-CSF into macrophages on d1. Dex treatment was applied on d4 for 24 h and all other assays (qRT-PCR and phagocytosis assays) were performed on d5.…”

Section: Irradiation-induced Thymus Atrophy C57bl/6 Mice and Mfg-e8mentioning

confidence: 99%

“…For immunoblot detection of MFG-E8 in cellular lysates, secretion was blocked by addition of 10 mg/ml Brefeldin A (Sigma) during the last 4 h of incubation. Non-reducing gradient SDS-PAGE and western blot analyses of whole cell lysates were performed as described previously 46,52 with 100 mg protein extract per lane and monoclonal mouse antibodies against human MFG-E8 (clone 1-H3) 44 and vinculin (Sigma) followed by ECL detection (GE Healthcare).…”

Section: Irradiation-induced Thymus Atrophy C57bl/6 Mice and Mfg-e8mentioning

confidence: 99%

Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids

et al. 2013

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The phagocytic clearance of apoptotic cells is essential to prevent chronic inflammation and autoimmunity. The phosphatidylserine-binding protein milk fat globule-EGF factor 8 (MFG-E8) is a major opsonin for apoptotic cells, and MFG-E8 À / À mice spontaneously develop a lupus-like disease. Similar to human systemic lupus erythematosus (SLE), the murine disease is associated with an impaired clearance of apoptotic cells. SLE is routinely treated with glucocorticoids (GCs), whose anti-inflammatory effects are consentaneously attributed to the transrepression of pro-inflammatory cytokines. Here, we show that the GC-mediated transactivation of MFG-E8 expression and the concomitantly enhanced elimination of apoptotic cells constitute a novel aspect in this context. Patients with chronic inflammation receiving high-dose prednisone therapy displayed substantially increased MFG-E8 mRNA levels in circulating monocytes. MFG-E8 induction was dependent on the GC receptor and several GC response elements within the MFG-E8 promoter. Most intriguingly, the inhibition of MFG-E8 induction by RNA interference or genetic knockout strongly reduced or completely abolished the phagocytosis-enhancing effect of GCs in vitro and in vivo. Thus, MFG-E8-dependent promotion of apoptotic cell clearance is a novel anti-inflammatory facet of GC treatment and renders MFG-E8 a prospective target for future therapeutic interventions in SLE.

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Release of lysophospholipid ‘find-me’ signals during apoptosis requires the ATP-binding cassette transporter A1

Cited by 47 publications

References 21 publications

Mitochondria and AMP-activated Protein Kinase-dependent Mechanism of Efferocytosis

Mitochondria and AMP-activated Protein Kinase-dependent Mechanism of Efferocytosis

Calcium-independent phospholipases A2 and their roles in biological processes and diseases

Milk fat globule-EGF factor 8 mediates the enhancement of apoptotic cell clearance by glucocorticoids

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