Параоксоназа: универсальный фактор антиоксидантной защиты организма человека

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents.Параоксоназы – это семейство ферментов, представленное PON1, PON2 и PON3, которые обладают широкой специфичностью и каталитической универсальностью. PON1 и PON3 циркулируют в плазме в состоянии, связанном с липопротеинами высокой плотности, предотвращают окисление липропротеинов, уменьшают образование липидных пероксидов и снижают риск развития атеросклероза. PON2 является внутриклеточным ферментом и не обнаруживается в плазме.  PON2 обнаружена во многих тканях организма, включая печень, легкие, трахею, почки, сердце, поджелудочную железу, тонкий кишечник, мышцы, семенники и эндотелиальные клетки. PON2 также присутствует в дофаминергических областях головного мозга и в астроцитах. На субклеточном уровне, PON2 локализуется в митохондриях, где предотвращает накопление триглицеридов и развитие окислительного стресса. PON3 - последняя из открытых параоксоназ обладает более выраженной антиксидантной активностью. PON3 обнаружена в клетках кожи, слюнных железах, железистом эпителии желудка, кишечника, эндометрии, гепатоцитах,  клетках поджелудочной железы, сердце, жировой ткани и в легочном эпителии. PON3 недостаточно изучена, но доказано ее антиоксидантное, противовоспалительное и противомикробное действие  за счет блокирования кворум-зависимых систем бактерий. Избыточная экспрессия PON3 уменьшает образование атеросклеротических бляшек и препятствует развитию ожирения, количество PON3 увеличивается при онкологических заболеваниях, повышая сопротивление опухолевых клеток к оксидативному стрессу и апоптозу. В обзоре представлена информация о физиологической роди параоксоназ, а также их участии в развитии заболеваний, ассоциированных с окислительным стрессом (атеросклероз, эндометриоз, болезнь Паркинсона, цирроз печени, бактериальные и вирусные инфекции и опухолевые процессы)

Paraoxonase: The universal factor of antioxidant defense in Human Body

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents

The role of paraoxonases in the pathogenesis of inflammatory and infectious diseases and cancer

The paraoxonase (PON) gene family contains three members: PON1, PON2, and PON3. All the three members of the family possess antioxidant properties and lipo-lactonase activity, and play a role in the pathogenesis of many inflammatory diseases, including atherosclerosis, Alzheimer’s and Parkinson’s diseases, diabetes mellitus, and cancer. Recent studies have demonstrated that the intracellular paraoxonases PON2 and PON3 associated with mitochondria and mitochondria-associated endoplasmic reticulum membranes regulate mitochondrial superoxide production and prevent apoptosis. As oxidative stress is a result of mitochondrial dysfunction and is involved in the development of inflammatory diseases, including atherosclerosis and cancer, the studies of the enzymes PON2 and PON3 can initiate many epidemiological surveys conducted to search for a relationship between the paraoxonase genes and the development of many inflammatory diseases. Understanding these mechanisms will be able to introduce new treatments for oxidative stress-related diseases. © Bionika Media Ltd.. All rights reserved

Paraoxonase: The universal factor of antioxidant defense in Human Body

The paraoxonase (PON) gene family includes three members: PON1, PON2, and PON3 aligned in tandem on chromosome 7 in humans. All PON proteins share considerable structural homology and have the capacity to protect cells from oxidative stress; therefore, they have been implicated in the pathogenesis of several inflammatory diseases, particularly atherosclerosis. Increased production of reactive oxygen species as a result of decreased activities of mitochondrial electron transport chain complexes plays a role in the development of many inflammatory diseases, including atherosclerosis. PON1 and PON3 proteins can be detected in plasma and reside in the high-density lipoprotein fraction and protect against oxidative stress by hydrolyzing certain oxidized lipids in lipoproteins, macrophages, and atherosclerotic lesions. Paraoxonase 2 (PON2) possesses antiatherogenic properties and is associated with lower ROS levels. PON2 is involved in the antioxidative and anti-inflammatory response in intestinal epithelial cells. In contrast to PON1 and PON3, PON2 is cell-associated and is not found in plasma. It is widely expressed in a variety of tissues, including the kidney, and protects against cellular oxidative stress. Overexpression of PON2 reduces oxidative status, prevents apoptosis in vascular endothelial cells, and inhibits cell-mediated low density lipoprotein oxidation. PON2 also inhibits the development of atherosclerosis, via mechanisms involving the reduction of oxidative stress. In this review we explore the physiological roles of PON in disease development and modulation of PONs by infective (bacterial, viral) agents

Placental expression level of the PON1, PON2, and PON3 genes in pstients with uncomplicated pregnancy and preeclampsia

Objective. To determine the expression level of the genes encoding the paraoxonase family enzymes (PON1, PON2, and PON3) in the placentas of women with uncomplicated pregnancy and in the development of preeclampsia Materials and methods. The investigation enrolled 26 pregnant women aged 24 to 35 years, including 14 women with normal pregnancy and 12 with preeclampsia. The expression of the PON1, PON2, and PON3 genes was analyzed by real-time PCR using the primers specific to these genes. Results. Women whose pregnancy was complicated by preeclampsia showed a significant decrease in the placental expression of the PON2 gene. The lowest PON2 gene expression was found in the placentas of women with severe preeclampsia. There were no significant differences in the placental expression level of the PON1 and PON3 genes in women with preeclampsia compared to healthy women. Conclusion. In women with preeclampsia, the placental PON2 gene expression decreases; however, the expression level of the PON1 and PON3 genes does not differ from that of the PON1 and PON3 genes in the placentas of patients with physiological pregnancy. The placental expression of the PON2 gene depends on the severity of preeclampsia; is lower in severe preeclampsia than in moderate preeclampsia. © Bionika Media Ltd

Placental expression level of the PON1, PON2, and PON3 genes in pstients with uncomplicated pregnancy and preeclampsia

Objective. To determine the expression level of the genes encoding the paraoxonase family enzymes (PON1, PON2, and PON3) in the placentas of women with uncomplicated pregnancy and in the development of preeclampsia Materials and methods. The investigation enrolled 26 pregnant women aged 24 to 35 years, including 14 women with normal pregnancy and 12 with preeclampsia. The expression of the PON1, PON2, and PON3 genes was analyzed by real-time PCR using the primers specific to these genes. Results. Women whose pregnancy was complicated by preeclampsia showed a significant decrease in the placental expression of the PON2 gene. The lowest PON2 gene expression was found in the placentas of women with severe preeclampsia. There were no significant differences in the placental expression level of the PON1 and PON3 genes in women with preeclampsia compared to healthy women. Conclusion. In women with preeclampsia, the placental PON2 gene expression decreases; however, the expression level of the PON1 and PON3 genes does not differ from that of the PON1 and PON3 genes in the placentas of patients with physiological pregnancy. The placental expression of the PON2 gene depends on the severity of preeclampsia; is lower in severe preeclampsia than in moderate preeclampsia. © Bionika Media Ltd

The expression level of paraoxonases in cervical dysplastic processes

Objective. To study the level of expression of paraoxonases (PONs) in the cervical epithelium of healthy women and that of female patients with cervical dysplastic processes. To comparatively analyze the expression level of PON1, PON2, and PON3 between the groups. To identify the relationship of changes in the level of expression of PONs to the development of cervical dysplastic processes. Subjects and methods. The investigation covered 47 patients who were divided into 3 groups: 1) 16 patients with CIN I-II; 2) 17 patients with CIN II-III; 3) 14 healthy women. The expression of paraoxonases was analyzed by real-time PCR using primers specific to these genes. Results. The authors found a significant increase in the expression level of the PON3 gene in the cervical epithelium of women with cervical dysplastic processes compared to the control group. There were no significant differences in the level of PON2 expression between the two groups. PON1 gene expression was unidentified in all the samples. Conclusion. During the investigation, the authors found a clear relationship between the higher expression of PON3 and the presence of CIN. The findings suggest that the enzyme PON3 may play a role in the development of dysplastic processes; therefore, determination of the level of PON3 expression may possess certain clinical potential in the diagnosis of precancerous cervical diseases. Thus, further researches in this area are required to develop new prognostic markers for the diagnosis of cervical dysplasia and diagnostic markers for the transition of CIN to cancer, which will be able to improve the quality of early diagnosis of precancerous diseases of the cervix and to optimize differentiated treatment policy. © 2020, Bionika Media Ltd. All rights reserved