PON1 lactonase activity and its association with cardiovascular disease

Murillo-González, F.E.; Ponce-Ruíz, N.; Rojas-García, Aurora Elizabeth; Rothenberg, Stephen J.; Bernal-Hernández, Yael Yvette; Cerda‐Flores, Ricardo M.; Mackness, Mike; Barrón-Vivanco, Briscia Socorro; González-Arias, Cyndia Azucena; Ponce-Gallegos, J.; Medina-Díaz, Irma Martha

doi:10.1016/j.cca.2019.09.016

Cited by 16 publications

(18 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Srećković et al have shown [18]. However, in the opinion of authors we agree with these later findings as metabolic risk clustering with emerging evidence is ever evolving field and more and newer CVD biomarkers depictive of underlying inflammation and atherosclerotic plaque behavior are now entering clinical market [19]. Moreover, the role of genetics and epigenetics in the absence or presence of metabolic syndrome label, as per the newer evidence is probably more informative in risk prediction than simply quantifying biochemical risk predictor [20] [21].…”

Section: Discussionsupporting

confidence: 81%

Mathematical Translation of Metabolic Syndrome: Assessment of siMS Score for Metabolic Syndrome and Biochemical Risks

Khan¹,

Khan²,

Hashmat³

et al. 2020

OJEMD

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 81%

Mathematical Translation of Metabolic Syndrome: Assessment of siMS Score for Metabolic Syndrome and Biochemical Risks

Khan¹,

Khan²,

Hashmat³

et al. 2020

OJEMD

View full text Add to dashboard Cite

show abstract

“…We chose to analyze PON1 lactonase activity (by hydrolysis of 5-thiobutyl butyrolactone [TBBL]) ( 33 ) rather than PON1 arylesterase and phosphotriesterase activity because lactonase activity was reported to more accurately reflect serum PON1 activity associated with HDL than paraoxonase or arylesterase activity ( 34 ). Reductions in PON1 lactonase activity have been shown to be better biomarkers of cardiovascular disease than reductions in arylesterase and phosphotriesterase activity ( 11 ).…”

Section: Resultsmentioning

confidence: 99%

“…Individuals with atherosclerotic cardiovascular disease consistently show reduced circulating PON1 activity ( 11 , 12 , 13 , 38 , 39 ). Association of MPO with HDL has previously been shown to reduce the PON1 activity of HDL ( 21 , 26 ) and to correlate with increased atherosclerosis ( 40 ).…”

Section: Discussionmentioning

confidence: 99%

“…Our studies with IsoLG focused exclusively on PON1 lactonase and antiperoxidation activities. Multiple substrates have previously been used to measure PON1 activity and its relationship to disease ( 3 , 5 , 11 , 12 , 13 , 14 , 15 , 16 , 44 , 45 ). In addition to its lactonase and antiperoxidation activity, PON1 exerts arylesterase activity ( e.g.…”

Section: Discussionmentioning

confidence: 99%

“…Structure–activity relationship studies and directed evolution studies support the notion that the lactonase activity is PON1’s primary native activity ( 2 , 3 , 4 , 5 , 6 , 7 ). Furthermore, lactonase activity appears to be a better biomarker of cardiovascular disease than arylesterase and phosphotriesterase activity ( 11 ). That PON1’s antiatherosclerotic activities are primarily due to its lactonase, and antiperoxidation activity is further supported by studies with PON3, which lacks paraoxonase and arylesterase activity while retaining similar lactonase and antiperoxidation activity to PON1 ( 46 ).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Myeloperoxidase-induced modification of HDL by isolevuglandins inhibits paraoxonase-1 activity

Aggarwal

May-Zhang

Yermalitsky

et al. 2021

Journal of Biological Chemistry

View full text Add to dashboard Cite

Reduced activity of paraoxonase 1 (PON1), a high-density lipoprotein (HDL)-associated enzyme, has been implicated in the development of atherosclerosis. Post-translational modifications of PON1 may represent important mechanisms leading to reduced PON1 activity. Under atherosclerotic conditions, myeloperoxidase (MPO) is known to associate with HDL. MPO generates the oxidants hypochlorous acid and nitrogen dioxide, which can lead to post-translational modification of PON1, including tyrosine modifications that inhibit PON1 activity. Nitrogen dioxide also drives lipid peroxidation, leading to the formation of reactive lipid dicarbonyls such as malondialdehyde and isolevuglandins, which modify HDL and could inhibit PON1 activity. Because isolevuglandins are more reactive than malondialdehyde, we used in vitro models containing HDL, PON1, and MPO to test the hypothesis that IsoLG formation by MPO and its subsequent modification of HDL contributes to MPO-mediated reductions in PON1 activity. Incubation of MPO with HDL led to modification of HDL proteins, including PON1, by IsoLG. Incubation of HDL with IsoLG reduced PON1 lactonase and antiperoxidation activities. IsoLG modification of recombinant PON1 markedly inhibited its activity, while irreversible IsoLG modification of HDL before adding recombinant PON1 only slightly inhibited the ability of HDL to enhance the catalytic activity of recombinant PON1. Together, these studies support the notion that association of MPO with HDL leads to lower PON1 activity in part via IsoLG-mediated modification of PON1, so that IsoLG modification of PON1 could contribute to increased risk for atherosclerosis, and blocking this modification might prove beneficial to reduce atherosclerosis.

show abstract

Evaluation of Naphthalenylmethylen Hydrazine Derivatives as Potent Inhibitors on, Antiatherogenic Enzymes, Paraoxonase I and Acetylcholinesterase Activities

2022

View full text Add to dashboard Cite

Acetylcholinesterase (AChE) and paraoxonase 1 (PON1) are two important serum ester hydrolases that have antiatherosclerotic effect by inhibiting the oxidation of lipid peroxides. In addition, AChE inhibitors are target molecules for the treatment of Alzheimer's. Naphthalene derivatives are important molecules in the field of pharmacology due to their wide range of biological activities. In this study, the inhibition effects of naphthalenylmethylen hydrazine derivatives on these two metabolic enzymes were investigated. IC 50 values of these molecules were determined in the range of 0.158 μM to 6.862 μM against PON1, 0.0214 μM to 0.675 μM against AChE. As a result, naphthalenylmethylen hydrazine derivatives had strong inhibition effect on both enzymes. In this context, we hope that the results obtained in this study contribute to the determination of the side effects of current and new naphthalene-based pharmacological compounds to be developed. And also be effective in the synthesis studies of new AChE inhibitors.

show abstract

PON1 lactonase activity and its association with cardiovascular disease

Cited by 16 publications

References 43 publications

Mathematical Translation of Metabolic Syndrome: Assessment of siMS Score for Metabolic Syndrome and Biochemical Risks

Mathematical Translation of Metabolic Syndrome: Assessment of siMS Score for Metabolic Syndrome and Biochemical Risks

Myeloperoxidase-induced modification of HDL by isolevuglandins inhibits paraoxonase-1 activity

Evaluation of Naphthalenylmethylen Hydrazine Derivatives as Potent Inhibitors on, Antiatherogenic Enzymes, Paraoxonase I and Acetylcholinesterase Activities

Contact Info

Product

Resources

About