Paraoxonases function as unique protectors against cardiovascular diseases and diabetes: Updated experimental and clinical data

Abstract

Paraoxonase (PON) refers to a family of three enzymes, namely PON1, PON2, and PON3. PON1 and PON3 are found in circulation bound to high-density lipoprotein, whereas PON2 is an intracellular protein. PON1 was first discovered as an enzyme to hydrolyze the organophosphate pesticide paraoxon, an activity that both PON2 and PON3 lack. All three PON enzymes are able to degrade oxidized lipids and protect against oxidative stress. PON enzymes also act to suppress inflammation. Animal studies show a critical role for PON enzymes, especially PON1 in protecting against cardiovascular diseases and related disorders, including diabetes and metabolic syndrome. In line with the findings in experimental animals, accumulating evidence from clinical research also indicates that PON enzymes function as potential protectors in human cardiovascular diseases and related disorders. Identification of PON enzymes as important players in cardiovascular health will facilitate the development of novel preventive and therapeutic modalities targeting PON enzymes to combat cardiovascular diseases and related disorders, which collectively constitute the chief contributors to the global burden of disease. This review describes the biochemical properties and molecular regulation of PON and summarizes the major recent findings on the functions of PON in protecting against cardiovascular diseases and related disorders.

Paraoxonase 2 protects against oxygen-glucose deprivation/reoxygenation-induced neuronal injury by enhancing Nrf2 activation via GSK-3β modulation

“…11 PON2 dysregulation has been implicated in a large number of diseases, including cancers, diabetes, and coronary artery diseases. [12][13][14] A growing body of evidence suggests that this protein functions as a powerful antioxidant. 9,15,16 PON2 can retard atherosclerosis progression by slowing foam cell formation through oxidative stress reduction.…”

Association between oxidative stress biomarkers and PON and GST polymorphisms as a predictor for susceptibility to the effects of pesticides

“…PON2 has also been suggested as an alternative potential treatment for Parkinson's disease, functioning as an endogenous antioxidant system (38), or playing a role in the etiology of noise-induced hearing loss (39). The antioxidant properties of PONs seem to be useful in the prevention and treatment of cardiovascular diseases and related disorders, as PON2 reduces oxidative stress in vascular cells protecting against cell-mediated oxidation of LdL (40). Others also have investigated the role of PON2, although with weak results (41).…”

From Gut to Brain: Uncovering Potential Serum Biomarkers Connecting Inflammatory Bowel Diseases to Neurodegenerative Diseases

“…They encompass three isoforms, namely PON1, PON2 and PON3. PON1 is the most extensively studied member of the family and is known for its ability to hydrolyze the organophosphate pesticide paraoxon [240][241][242]. These enzymes are primarily associated with HDLcholesterol and have been implicated in protection against oxidative stress, inflammation, and cardiovascular diseases.…”