Paraoxonase-2 Reduces Oxidative Stress in Vascular Cells and Decreases Endoplasmic Reticulum Stress–Induced Caspase Activation

Horke, Sven; Witte, Ines; Wilgenbus, Petra; Krüger, Maximilian; Strand, Dennis; Förstermann, Ulrich

doi:10.1161/circulationaha.106.681700

Cited by 230 publications

(273 citation statements)

References 36 publications

Supporting

Mentioning

253

Contrasting

Unclassified

Order By: Relevance

“…The finding that ER stress pathways are all reduced following δPKC inhibition at the onset of reperfusion strongly supports this hypothesis. The involvement of oxidative stress in ER dysfunction has been well documented [42,43]. One possibility may be that δV1-1 reduces ER stress-induced oxidative stress, which subsequently initiates ER stress response pathways.…”

Section: Discussionmentioning

confidence: 99%

δPKC participates in the endoplasmic reticulum stress-induced response in cultured cardiac myocytes and ischemic heart

Vallentin

Churchill

et al. 2007

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

The cellular response to excessive endoplasmic reticulum (ER) stress includes the activation of signaling pathways, which lead to apoptotic cell death. Here we show that treatment of cultured cardiac myocytes with tunicamycin, an agent that induces ER stress, causes the rapid translocation of δPKC to the ER. We further demonstrate that inhibition of δPKC using the δPKC-specific antagonist peptide, δV1-1, reduces tunicamycin-induced apoptotic cell death, and inhibits expression of specific ER stress response markers such as CHOP, GRP78 and phosphorylation of JNK. The physiological importance of δPKC in this event is further supported by our findings that the ER stress response is also induced in hearts subjected to ischemia and reperfusion injury and that this response also involves δPKC translocation to the ER. We found that the levels of the ER chaperone, GRP78, the spliced XBP-1 and the phosphorylation of JNK are all increased following ischemia and reperfusion and that δPKC inhibition by δV1-1 blocks these events. Therefore, ischemia-reperfusion injury induces ER stress in the myocardium in a mechanism that requires δPKC activity. Taken together, our data show for the first time that δPKC activation plays a critical role in the ER stressmediated response and the resultant cell death.

show abstract

Section: Discussionmentioning

confidence: 99%

δPKC participates in the endoplasmic reticulum stress-induced response in cultured cardiac myocytes and ischemic heart

Vallentin

Churchill

et al. 2007

Journal of Molecular and Cellular Cardiology

View full text Add to dashboard Cite

show abstract

“…Highly expressed in this group of patients with the worst outcome were genes (BMPR1B, CTGF [CCN2], TTYH2, IGJ, PON2, CD73, CDC42EP3, TSPAN7, and SEMA6A) involved in adaptive cell signaling responses to transforming growth factor ␤, stem cell function, B-cell development and differentiation, and the regulation of tumor growth. [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] These highest risk cases lacked expression of the genes (NR4A3, BTG3, RGS1, and RGS2) whose relatively high expression characterized the ALL cases with the best outcome. Not surprisingly, given that all cases with an activated kinase signature were assigned to the highest risk group with the combined classifier, 6 of the genes associated with our kinase signature (BMPR1B, ECM1, IGJ, PON2, SEMA6A, and TSPAN7) were contained within our gene expression classifier for RFS.…”

Section: Discussionmentioning

confidence: 99%

Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia

Kang

Chen

Wilson

et al. 2010

Blood

186

191

View full text Add to dashboard Cite

To determine whether gene expression profiling could improve outcome prediction in children with acute lymphoblastic leukemia (ALL) at high risk for relapse, we profiled pretreatment leukemic cells in 207 uniformly treated children with highrisk B-precursor ALL. A 38-gene expression classifier predictive of relapse-free survival (RFS) could distinguish 2 groups with differing relapse risks: low (4-year RFS, 81%, n ‫؍‬ 109) versus high (4-year RFS, 50%, n ‫؍‬ 98; P < .001). In multivariate analysis, the gene expression classifier (P ‫؍‬ .001) and flow cytometric measures of minimal residual disease (MRD; P ‫؍‬ .001) each provided independent prognostic information. Together, they could be used to classify children with high-risk ALL into low-(87% RFS), intermediate-(62% RFS), or high-(29% RFS) risk groups (P < .001). A 21-gene expression classifier predictive of end-induction MRD effectively substituted for flow MRD, yielding a combined classifier that could distinguish these 3 risk groups at diagnosis (P < .001). These classifiers were further validated on an independent highrisk ALL cohort (P ‫؍‬ .006) and retained independent prognostic significance (P < .001) in the presence of other recently described poor prognostic factors (IKAROS/IKZF1 deletions, JAK mutations, and kinase expression signatures

show abstract

“…Proteinase K treatment was carried out as described by Horke et al [16]. Briefly cells were cultured in six-well plates and treated with proteinase K (25 μg/ml, 37°C, 15 min) in PBS before addition of phenylmethylsulfonyl fluoride (5 mM) and lysis buffer.…”

Section: Proteinase K Treatmentmentioning

confidence: 99%

HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress

Deakin

Bioletto

Bochaton‐Piallat

et al. 2011

Free Radical Biology and Medicine

View full text Add to dashboard Cite

a b s t r a c t a r t i c l e i n f oParaoxonase-1 (PON1) is a high-density lipoprotein (HDL)-associated serum enzyme thought to make a major contribution to the antioxidant capacity of the lipoprotein. In previous studies, we proposed that HDL promoted PON1 secretion by transfer of the enzyme from its plasma membrane location to HDL transiently anchored to the hepatocyte. This study examined whether PON1 can be transferred into cell membranes and retain its enzymatic activities and functions. Using Chinese hamster ovary and human endothelial cells, we found that recombinant PON1 as well as PON1 associated with purified human HDL was freely exchanged between the external medium and the cell membranes. Transferred PON1 was located in the external face of the plasma membrane of the cells in an enzymatically active form. The transfer of PON1 led to a gain of function by the target cells, as revealed by significantly reduced susceptibility to oxidative stress and significantly increased ability to neutralize the bacterial virulence agent 3-oxo-C 12 -homoserine lactone. The data demonstrate that PON1 is not a fixed component of HDL and suggest that the enzyme could also exert its protective functions outside the lipoprotein environment. The observations may be of relevance to tissues exposed to oxidative stress and/or bacterial infection.

show abstract

Paraoxonase-2 Reduces Oxidative Stress in Vascular Cells and Decreases Endoplasmic Reticulum Stress–Induced Caspase Activation

Cited by 230 publications

References 36 publications

δPKC participates in the endoplasmic reticulum stress-induced response in cultured cardiac myocytes and ischemic heart

δPKC participates in the endoplasmic reticulum stress-induced response in cultured cardiac myocytes and ischemic heart

Gene expression classifiers for relapse-free survival and minimal residual disease improve risk classification and outcome prediction in pediatric B-precursor acute lymphoblastic leukemia

HDL-associated paraoxonase-1 can redistribute to cell membranes and influence sensitivity to oxidative stress

Contact Info

Product

Resources

About