Complement-mediated Activation of Calcium-independent Phospholipase A2γ

Elimam, Hanan; Papillon, Joan; Takano, Tomoko; Cybulsky, Andrey V.

doi:10.1074/jbc.m112.396614

Cited by 29 publications

(39 citation statements)

References 59 publications

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“…The purity of glomeruli obtained from the isolation was consistently ϳ70 -80%. Isolated glomeruli were seeded on type I collagencoated culture dishes for 5 days in K1 medium (11). A week after the first epithelial cell outgrowth, the cells were immortalized by infection with retrovirus carrying the temperature-sensitive SV40 large T antigen, which was performed by adding retrovirus-containing supernatants from 293T packaging cells (22,26).…”

Section: Methodsmentioning

confidence: 99%

“…(R)-Bromoenol lactone (R-BEL) was from Cayman Chemical (Ann Arbor, MI). Wild type (WT), M4, and S511A/S515A GFP-iPLA 2 ␥ cDNAs were described previously (11). Plasmids 5xATF6-GL3, pCGN-ATF6(1-373)m1, and low density lipoprotein receptor (LDLR) promoter-luciferase were from Addgene (Cambridge, MA) (20,21).…”

Section: Methodsmentioning

confidence: 99%

“…Cell Culture and Transfection-Rat GECs were derived from glomerular explants, and the methods for culture and characterization have been described previously (11,12,23). GECs were maintained in K1 medium on plastic substratum.…”

Section: Methodsmentioning

confidence: 99%

“…GECs were maintained in K1 medium on plastic substratum. Rat GECs stably transfected with GFP-iPLA 2 ␥ and control GECs were described previously (11). 293T and COS-1 cells were cultured in Dulbecco's modified Eagle's medium (DMEM) supplemented with 10% fetal bovine serum.…”

Section: Methodsmentioning

confidence: 99%

“…Various forms of glomerulonephritis are associated with podocyte injury, which leads to impaired glomerular permselectivity (proteinuria). We reported previously that complement C5b-9 activates iPLA 2 ␥ in GECs in a protein kinase-dependent manner (11) and that overexpression of iPLA 2 ␥ is protective against complement-dependent GEC injury (12). In GECs, iPLA 2 ␥ is localized at the ER and mitochondria, and this localization is dependent on the N-terminal region of iPLA 2 ␥ (11).…”

mentioning

confidence: 99%

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Calcium-independent Phospholipase A2γ Enhances Activation of the ATF6 Transcription Factor during Endoplasmic Reticulum Stress

Elimam

Papillon

Takano

et al. 2015

Journal of Biological Chemistry

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Background: Calcium-independent PLA 2 ␥ (iPLA 2 ␥) is a membrane-bound enzyme that localizes at the endoplasmic reticulum (ER). Results: iPLA 2 ␥ amplified activation of the ATF6 pathway of the unfolded protein response, resulting in up-regulation of ER chaperones and cytoprotection. Conclusion: iPLA 2 ␥ enhances activation of ATF6. Significance: Modulating iPLA 2 ␥ activity may provide opportunities for pharmacological intervention in glomerular diseases associated with ER stress.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Calcium-independent Phospholipase A2γ Enhances Activation of the ATF6 Transcription Factor during Endoplasmic Reticulum Stress

Elimam

Papillon

Takano

et al. 2015

Journal of Biological Chemistry

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Cytoprotective activity of mitochondrial uncoupling protein‐2 in lung and spleen

Jabůrek

Ježek

2018

FEBS Open Bio

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Mitochondrial uncoupling protein‐2 (UCP2) mediates free fatty acid (FA)‐dependent H+ translocation across the inner mitochondrial membrane (IMM), which leads to acceleration of respiration and suppression of mitochondrial superoxide formation. Redox‐activated mitochondrial phospholipase A2 (mt‐iPLA2γ) cleaves FAs from the IMM and has been shown to acts in synergy with UCP2. Here, we tested the mechanism of mt‐iPLA2γ‐dependent UCP2‐mediated antioxidant protection using lipopolysaccharide (LPS)‐induced pro‐inflammatory and pro‐oxidative responses and their acute influence on the overall oxidative stress reflected by protein carbonylation in murine lung and spleen mitochondria and tissue homogenates. We provided challenges either by blocking the mt‐iPLA2γ function by the selective inhibitor R‐bromoenol lactone (R‐BEL) or by removing UCP2 by genetic ablation. We found that the basal levels of protein carbonyls in lung and spleen tissues and isolated mitochondria were higher in UCP2‐knockout mice relative to the wild‐type (wt) controls. The administration of R‐BEL increased protein carbonyl levels in wt but not in UCP2‐knockout (UCP2‐KO) mice. LPS further increased the protein carbonyl levels in UCP2‐KO mice, which correlated with protein carbonyl levels determined in wt mice treated with R‐BEL. These results are consistent with the UCP2/mt‐iPLA2γ antioxidant mechanisms in these tissues and support the existence of UCP2‐synergic mt‐iPLA2γ‐dependent cytoprotective mechanism in vivo.

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Profile of the unfolded protein response in rat cerebellar cortical development

Naughton

McMahon

Healy

et al. 2019

J of Comparative Neurology

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The unfolded protein response (UPR) has been reported during normal development of cortical neurons and cerebellar white matter and may also contribute to the pathogenesis of neurological conditions, such as Marinesco‐Sjogren syndrome and Borna virus infection, which result in cerebellar defects. The UPR is initiated when the processing capacity of the endoplasmic reticulum (ER) is overwhelmed. Misfolded proteins accumulate and can activate ER stress sensors; PKR‐like endoplasmic reticulum kinase (PERK), inositol‐requiring enzyme 1 (IRE1), activated transcription factor 6 (ATF6) and their downstream targets glucose‐regulated protein 78 (GRP78), glucose‐regulated protein 94 (GRP94) and protein disulfide isomerase (PDI). In order to provide a fuller appreciation of the possible importance of ER stress‐associated proteins in the context of cerebellar disease, we have profiled the expression of ER stress sensors and their downstream targets in the developing cerebellar cortex in postnatal rat. Activation of PERK and IRE1 stress sensors was observed for the first time in normally developing granule cell precursors. A second proliferative pPERK‐positive population was also detected in the internal granular layer (IGL). In general, the density of UPR protein‐positive cells was found to decrease significantly when profiles in early and late postnatal ages were compared. These data may be relevant to studies of medulloblastoma and warrant further investigation.

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Complement-mediated Activation of Calcium-independent Phospholipase A2γ

Cited by 29 publications

References 59 publications

Calcium-independent Phospholipase A2γ Enhances Activation of the ATF6 Transcription Factor during Endoplasmic Reticulum Stress

Calcium-independent Phospholipase A2γ Enhances Activation of the ATF6 Transcription Factor during Endoplasmic Reticulum Stress

Cytoprotective activity of mitochondrial uncoupling protein‐2 in lung and spleen

Profile of the unfolded protein response in rat cerebellar cortical development

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