Paraoxonase 2 prevents the development of heart failure

Li, Wei; Kennedy, David J.; Shao, Zhili; Wang, Xi; Kamdar, Andre Klaassen; Weber, Malory; Mislick, Kayla; Kiefer, Kathryn; Morales, Rommel; Agatisa-Boyle, Brendan; Shih, Diana M.; Reddy, Srinivasa T.; Moravec, Christine S.; Tang, W.H. Wilson

doi:10.1016/j.freeradbiomed.2018.04.583

Cited by 22 publications

(21 citation statements)

References 41 publications

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“…In addition to the overall high OXPHOS scores, the stem-like signature was associated with enhanced expression of OXR1 and PON2 . Being essential for protection against oxidative stress, these genes may counteract higher reactive oxygen species (ROS) levels resulting from enhanced OXPHOS rates [ 34 , 35 ]. Another gene included in the stem-like signature is MAP2K6 —an essential p38 signaling component [ 36 ] known to be associated with high OXPHOS levels in intestinal stem cells [ 23 ] ( Figure S1f , Table S1 ).…”

Section: Resultsmentioning

confidence: 99%

Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer

Zowada

Tirier

Dieter

et al. 2021

Cancers

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Intra-tumor heterogeneity of tumor-initiating cell (TIC) activity drives colorectal cancer (CRC) progression and therapy resistance. Here, we used single-cell RNA-sequencing of patient-derived CRC models to decipher distinct cell subpopulations based on their transcriptional profiles. Cell type-specific expression modules of stem-like, transit amplifying-like, and differentiated CRC cells resemble differentiation states of normal intestinal epithelial cells. Strikingly, identified subpopulations differ in proliferative activity and metabolic state. In summary, we here show at single-cell resolution that transcriptional heterogeneity identifies functional states during TIC differentiation. Furthermore, identified expression signatures are linked to patient prognosis. Targeting transcriptional states associated to cancer cell differentiation might unravel novel vulnerabilities in human CRC.

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Section: Resultsmentioning

confidence: 99%

Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer

Zowada

Tirier

Dieter

et al. 2021

Cancers

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“…From 2010 it was highlighted PON2's ability to reduce oxidative stress in mitochondria and to prevent apoptosis in the endoplasmic reticulum [1-4] with a still unclarified mechanism suggested to be independent from the lactonase activity [1]. From here on scientists explored PON2 antioxidant effects, its role in preventing heart failure [5] and its involvement in any type of tumor [6].…”

Section: Introductionmentioning

confidence: 99%

Human Paraoxonase-2 (PON2): Protein Functions and Modulation

2021

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PON1, PON2, and PON3 belong to a family of lactone hydrolyzing enzymes endowed with various substrate specificities. Among PONs, PON2 shows the highest hydrolytic activity toward many acyl-homoserine lactones (acyl-HL) involved in bacterial quorum-sensing signaling. Accordingly, defense against pathogens, such as Brevundimonas aeruginosa (B. aeruginosa), was postulated to be the principal function of PON2. However, recent findings have highlighted the importance of PON2 in oxidative stress control, inhibition of apoptosis, and the progression of various types of malignancies. This review focuses on all of these aspects of PON2.

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“…As for PON1, we show for the first time that injection of rePON1 to mice decreases aortic cholesterol and TAG contents. Although PON1 is associated with HDL in the circulation, PON2 is expressed in various major organs as an intracellular enzyme, and is known for its atheroprotective and cardioprotective roles (Li et al, ; Ng et al, ; Rom and Aviram, ). Here, we found that rePON1 injection upregulated PON2 in the aorta, whereas both PJ consumption and rePON1 injection reduced Dgat1 expression, the key enzyme that catalyzes the final step in TAG biosynthesis by attaching a long‐chain fatty acyl‐CoA to diacylglycerol (Yen et al, ).…”

Section: Discussionmentioning

confidence: 99%

Exogenous (Pomegranate Juice) or Endogenous (Paraoxonase1) Antioxidants Decrease Triacylglycerol Accumulation in Mouse Cardiovascular Disease‐Related Tissues

Rom

Volkova

Jeries

et al. 2018

Lipids

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The polyphenol‐rich pomegranate juice (PJ) and the high‐density lipoprotein (HDL)‐associated paraoxonase1 (PON1) are known as potent atheroprotective antioxidants, but their effects on other tissues related to cardiovascular disease (CVD) remain unknown. The current study aimed to investigate the effects of treating mice with PJ or recombinant PON1 (rePON1) on the oxidation and lipid status of CVD‐related tissues: serum, aorta, heart, liver, kidney, visceral, and subcutaneous adipose tissues (VAT and SAT). Both PJ consumption and rePON1 injection decreased the serum levels of thiobarbituric acid‐reactive substances (16% and 19%) and triacylglycerols (TAG, 24% and 27%), while only rePON1 increased the levels of thiol groups (35%) and decreased serum cholesterol (15%). Both PJ and rePON1 significantly decreased aortic cholesterol (38% and 32%) and TAG (62% and 58%) contents in association with downregulation of the key TAG biosynthetic enzyme diacylglycerol O‐acyltransferase 1 (DGAT1, 71% and 65%), while only PJ decreased aortic lipid peroxides (47%). Substantial TAG‐lowering effects of both PJ and rePON1 were observed also in the heart (31% and 42%), liver (34% and 42%), and kidney (42% and 57%). In both VAT and SAT, rePON1 decreased the levels of lipid peroxides (28% and 25%), while PJ decreased the TAG content (22% and 18%). Ex vivo incubation of SAT with serum derived from mice that consumed PJ or injected with rePON1 decreased SAT lipid peroxides (35% or 28%) and TAG mass (12% or 10%). These novel findings highlight potent TAG‐lowering properties of exogenous (PJ) and endogenous (PON1) antioxidants in tissues associated with CVD.

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Paraoxonase 2 prevents the development of heart failure

Abstract: Our study suggests a cardioprotective role for PON2 in both experimental and human heart failure, which may be associated with the ability of PON2 to improve mitochondrial function and diminish ROS generation.

Cited by 22 publications

References 41 publications

Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer

Functional States in Tumor-Initiating Cell Differentiation in Human Colorectal Cancer

Human Paraoxonase-2 (PON2): Protein Functions and Modulation

Exogenous (Pomegranate Juice) or Endogenous (Paraoxonase1) Antioxidants Decrease Triacylglycerol Accumulation in Mouse Cardiovascular Disease‐Related Tissues

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