دورية أكاديمية

The Role of Phospholipase Activity of Peroxiredoxin 6 in Its Transmembrane Transport and Protective Properties.

التفاصيل البيبلوغرافية
العنوان: The Role of Phospholipase Activity of Peroxiredoxin 6 in Its Transmembrane Transport and Protective Properties.
المؤلفون: Sharapov MG; Institute of Cell Biophysics of the Russian Academy of Sciences, FRC PSCBR RAS, 142290 Pushchino, Russia., Goncharov RG; Institute of Cell Biophysics of the Russian Academy of Sciences, FRC PSCBR RAS, 142290 Pushchino, Russia., Parfenyuk SB; Institute of Cell Biophysics of the Russian Academy of Sciences, FRC PSCBR RAS, 142290 Pushchino, Russia., Glushkova OV; Institute of Cell Biophysics of the Russian Academy of Sciences, FRC PSCBR RAS, 142290 Pushchino, Russia., Novoselov VI; Institute of Cell Biophysics of the Russian Academy of Sciences, FRC PSCBR RAS, 142290 Pushchino, Russia.
المصدر: International journal of molecular sciences [Int J Mol Sci] 2022 Dec 03; Vol. 23 (23). Date of Electronic Publication: 2022 Dec 03.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: MDPI Country of Publication: Switzerland NLM ID: 101092791 Publication Model: Electronic Cited Medium: Internet ISSN: 1422-0067 (Electronic) Linking ISSN: 14220067 NLM ISO Abbreviation: Int J Mol Sci Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Basel, Switzerland : MDPI, [2000-
مواضيع طبية MeSH: Peroxiredoxin VI*/genetics , Peroxiredoxin VI*/metabolism , Peroxidase*/metabolism, Mice ; Animals ; Phospholipases A2/metabolism ; Antioxidants/pharmacology ; Antioxidants/metabolism ; Peroxidases ; Mammals/metabolism
مستخلص: Peroxiredoxin 6 (Prdx6) is a multifunctional eukaryotic antioxidant enzyme. Mammalian Prdx6 possesses peroxidase activity against a wide range of organic and inorganic hydroperoxides, as well as exhibits phospholipase A2 (aiPLA2) activity, which plays an important role in the reduction of oxidized phospholipids and cell membrane remodeling. Exogenous Prdx6 has recently been shown to be able to penetrate inside the cell. We hypothesized that this entry may be due to the phospholipase activity of Prdx6. Experiments using exogenous Prdx6 in three cell lines (3T3, A549, RAW 264.7) demonstrated that it is the phospholipase activity that promotes its penetration into the cell. Overoxidation of Prdx6 led to a suppression of the peroxidase activity and a 3-to-4-fold growth of aiPLA2, which enhanced the efficiency of its transmembrane transport into the cells by up to 15 times. A mutant form of Prdx6-S32A with an inactivated phospholipase center turned out to be unable to enter the cells in both the reduced and oxidized state of the peroxidase active center. Previously, we have shown that exogenous Prdx6 has a significant radioprotective action. However, the role of phospholipase activity in the radioprotective effects of Prdx6 remained unstudied. Trials with the mutant Prdx6-S32A form, with the use of a total irradiation model in mice, showed a nearly 50% reduction of the radioprotective effect upon aiPLA2 loss. Such a significant decrease in the radioprotective action may be due to the inability of Prdx6-S32A to penetrate animal cells, which prevents its reduction by the natural intracellular reducing agent glutathione S-transferase (πGST) and lowers the efficiency of elimination of peroxides formed from the effect of ionizing radiation. Thus, phospholipase activity may play an important role in the reduction of oxidized Prdx6 and manifestation of its antioxidant properties.
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معلومات مُعتمدة: 20-015-00216А Russian Foundation for Basic Research
فهرسة مساهمة: Keywords: ionizing radiation; oxidative stress; peroxiredoxin 6 (Prdx6); phospholipase A2; radioprotection; transmembrane transport of proteins
المشرفين على المادة: EC 1.11.1.15 (Peroxiredoxin VI)
EC 1.11.1.7 (Peroxidase)
EC 3.1.1.4 (Phospholipases A2)
0 (Antioxidants)
EC 1.11.1.- (Peroxidases)
تواريخ الأحداث: Date Created: 20221211 Date Completed: 20221216 Latest Revision: 20221221
رمز التحديث: 20240628
مُعرف محوري في PubMed: PMC9738660
DOI: 10.3390/ijms232315265
PMID: 36499590
قاعدة البيانات: MEDLINE
الوصف
تدمد:1422-0067
DOI:10.3390/ijms232315265