Activation of group IVC phospholipase A2 by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells

Tithof, Patricia K.; Richards, Sean; Elgayyar, Mona; Menn, Fu-Minn; Vulava, Vijay M.; McKay, Larry D.; Sanseverino, John; Sayler, Gary S.; Tucker, Dawn E.; Leslie, Christina C.; Lu, Kim P.; Ramos, Kenneth S.

doi:10.1007/s00204-010-0614-9

Cited by 7 publications

(3 citation statements)

References 38 publications

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“…Thus there are myriad opportunities to assess the effects of toxins such as heavy metals at (by definition) physiologically relevant levels on development. Not surprisingly, higher levels of abnormalities have been found in such animals relative to animals in nearby uncontaminated sites …”

Section: Effects Of Exogenous Agents On Developmentmentioning

confidence: 96%

Peromyscus (deer mice) as developmental models

Vrana

Shorter

Szalai

et al. 2013

WIREs Developmental Biology

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Deer mice (Peromyscus) are the most common native North American mammals, and exhibit great natural genetic variation. Wild-derived stocks from a number of populations are available from the Peromyscus Genetic Stock Center (PGSC). The PGSC also houses a number of natural variants and mutants (many of which appear to differ from Mus). These include metabolic, coat-color/pattern, neurological, and other morphological variants/mutants. Nearly all these mutants are on a common genetic background, the Peromyscus maniculatus BW stock. Peromyscus are also superior behavior models in areas such as repetitive behavior and pair-bonding effects, as multiple species are monogamous. While Peromyscus development generally resembles that of Mus and Rattus, prenatal stages have not been as thoroughly studied, and there appear to be intriguing differences (e.g., longer time spent at the two-cell stage). Development is greatly perturbed in crosses between P. maniculatus (BW) and Peromyscus polionotus (PO). BW females crossed to PO males produce growth-restricted, but otherwise healthy, fertile offspring which allows for genetic analyses of the many traits that differ between these two species. PO females crossed to BW males produce overgrown but severely dysmorphic conceptuses that rarely survive to late gestation. There are likely many more uses for these animals as developmental models than we have described here. Peromyscus models can now be more fully exploited due to the emerging genetic (full linkage map), genomic (genomes of four stocks have been sequenced) and reproductive resources.

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Section: Effects Of Exogenous Agents On Developmentmentioning

confidence: 96%

Peromyscus (deer mice) as developmental models

Vrana

Shorter

Szalai

et al. 2013

WIREs Developmental Biology

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“…Yapılan bir çalışmada sigara dumanının NADPH oksidaz enziminin aktivitesini indükleyerek hücre içi süperoksit radikallerinin üretimini arttırdığı ve bu artışın da sitozolik fosfolipaz A2 enzim düzeyini yükselttiği gösterilmiştir. Bu artışın proinflamatuar gen transkripsiyonunu aktifleyen MAPKs yolağı, NF-kB, ve AP-1 faktörlerinden kaynaklandığı gösterilmiştir (25). Yapılan bir başka çalışmada da benzer şekilde sigara dumanının siklooksijenaz-2 enzimini arttırdığı ortaya konmuştur.…”

Section: şEkilunclassified

Si̇gara Dumaninin Neden Olduğu Akci̇ğer İnflamasyonuna Karşi Alfa-Li̇noleni̇k Asi̇ti̇n Koruyucu Rolü

Kaplan¹,

Doran²

2016

Mustafa Kemal Üniversitesi Tıp Dergisi

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Amaç: Yapılan çalışmalar keten yağında bolca bulunan ve omega 3 yağ asitlerinden biri olan alfa-linolenik asitin antioksidan ve anti inflamatuar etkinliğini göstermiştir. Sigara dumanı birçok zararlı bileşeni içerdiğinden akceğerlerde hasara neden olmaktadır. Bu nedenle alfa-linolenik asitin sigara dumanı maruziyetine bağlı akciğer hasarına karşı koruyucu etkinliği olup olmayacağını planladık.Gereç ve Yöntem: Bu amaçla ferelere 2 ay boyunca sigara dumanı ve 200 mg/kg alfa-linolenik asit verildi. ve akciğerlerindeki siklooksijenaz-2, fosfolipaz A2 ve indüklenebilir nitrik oksit sentaz (iNOS) enzimleri ELISA yöntemiyle analiz edildi. Bulgular:Farelere gentamisin uygulaması akciğerlerde siklooksijenaz-2(COX-2), fosfolipaz A2 ve iNOS enzimlerinin ekpresyonlarını arttırdı. Sigara dumanına maruz bırakılan farelere alfa-linolenik asit verilmesi bu enzimlerdeki artışı geri çevirdi.Sonuç: Çalışmamız sigaranın neden olduğu akciğer hasarına karşı alfa-linolenik asit kullanılmasının yararlı olacağını göstermiştir.

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“…However, few studies have explored the direct impact of tar on atherosclerosis progression. Certain polycyclic aromatic hydrocarbons in tar have been found to activate phospholipase A2 in human coronary artery endothelial cells, leading to apoptosis as well as inducing a proinflammatory state in macrophages [7][8][9]. Despite the reported association of certain components of tar with atherosclerosis, the underlying mechanisms of the pro-atherosclerotic effects of tar remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Cigarette tar accelerates atherosclerosis progression via RIPK3-dependent necroptosis mediated by endoplasmic reticulum stress in vascular smooth muscle cells

Bai,

Wang,

Luo

et al. 2024

Cell Commun Signal

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Background Tar is the main toxic of cigarettes, and its effect on atherosclerosis progression and the underlying mechanisms remain largely unknown. Vascular smooth muscle cells (VSMCs) play a key role in atherogenesis and plaque vulnerability. The present study sought to investigate the mechanism of atherosclerosis progression through tar-induced VSMC necroptosis, a recently described form of necrosis. Methods The effect of tar on atherosclerosis progression and VSMC necroptosis was examined in ApoE−/− mice and cultured VSMCs. The role of necroptosis in tar-induced plaque development was evaluated in RIPK3-deletion mice (ApoE−/−RIPK3−/−). The key proteins of necroptosis in carotid plaques of smokers and non-smokers were also examined. Quantitative proteomics of mice aortas was conducted to further investigate the underlying mechanism. Pharmacological approaches were then applied to modulate the expression of targets to verify the regulatory process of tar-induced necroptosis. Results Tar administration led to increased atherosclerotic plaque area and reduced collagen and VSMCs in ApoE−/− mice. The expression of RIPK1、RIPK3、and MLKL in VSMCs of plaques were all increased in tar-exposed mice and smokers. RIPK3 deletion protected against VSMC loss and plaque progression stimulated by tar. In mechanistic studies, quantitative proteomics analysis of ApoE−/− mice aortas suggested that tar triggered endoplasmic reticulum (ER) stress. PERK-eIF2α-CHOP axis was activated in tar-treated VSMCs and atherosclerotic plaque. Inhibition of ER stress using 4PBA significantly reduced plaque progression and VSMC necroptosis. Further study revealed that ER stress resulted in calcium (Ca2+) release into mitochondria and cytoplasm. Elevated Ca2+ levels lead to mitochondrial dysfunction and excessive reactive oxygen species (ROS) production, which consequently promote RIPK3-dependent necroptosis. In addition, Ca2+/calmodulin-dependent protein kinase II (CaMKII) activated by cytosolic Ca2+ overload binds to RIPK3, accounting for necroptosis. Conclusion The findings revealed that cigarette tar promoted atherosclerosis progression by inducing RIPK3-dependent VSMC necroptosis and identified novel avenues of ER stress and Ca2+ overload.

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Activation of group IVC phospholipase A2 by polycyclic aromatic hydrocarbons induces apoptosis of human coronary artery endothelial cells

Cited by 7 publications

References 38 publications

Peromyscus (deer mice) as developmental models

Peromyscus (deer mice) as developmental models

Si̇gara Dumaninin Neden Olduğu Akci̇ğer İnflamasyonuna Karşi Alfa-Li̇noleni̇k Asi̇ti̇n Koruyucu Rolü

Cigarette tar accelerates atherosclerosis progression via RIPK3-dependent necroptosis mediated by endoplasmic reticulum stress in vascular smooth muscle cells

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