Non-Mammalian Prdx6 Enzymes (Proteins with 1-Cys Prdx Mechanism) Display PLA(2) Activity Similar to the Human Orthologue

Author(s)

Bannitz-Fernandes, Renata ^[1] ; Aleixo-Silva, Rogerio ^[1] ; Silva, Joao Paulo ^[1] ; Dodia, Chandra ^[2] ; Vazquez-Medina, Jose Pablo ^{[3, 2]} ; Tao, Jian-Qin ^[2] ; Fisher, Aron ^[2] ; Netto, Luis ^[1]

Affiliation

^[1] Univ Sao Paulo, Inst Biociencias, Dept Genet & Biol Evolut, BR-05508090 Sao Paulo, SP - Brazil

^[2] Univ Penn, Perelman Sch Med, Inst Environm Med, Dept Physiol, Philadelphia, PA 19104 - USA

^[3] Univ Calif Berkeley, Dept Integrat Biol, Berkeley, CA 94720 - USA

• Document type: Journal article
• Source: ANTIOXIDANTS; v. 8, n. 3 MAR 1 2019.
• Web of Science Citations: 1

Abstract

Mammalian peroxiredoxin class 6 (Prdx6) are bifunctional enzymes. Non-mammalian Prdx6 enzymes display Cys-based peroxidase activity, but to date their putative phospholipase A(2) (PLA(2) activities) has not been experimentally investigated. Initially, we observed that five non-mammalian Prdx6 enzymes (enzymes from Arabidopsis thaliana (AtPER1), Triticum aestivum (TaPER1), Pseudomonas aeruginosa (PaLsfA) and Aspergillus fumigatus (AfPrx1 and AfPrxC)) present features compatible with PLA(2) activities in mammalian Prdx6 by amino acid sequences alignment and tertiary structure modeling. Employing unilamellar liposomes with tracer amounts of {[}H-3]-1,2-Dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and thin layer chromatography, all the tested non-mammalian Prdx6 enzymes displayed PLA(2) activities, with values ranging from 3.4 to 6.1 nmol/min/mg protein. It was previously shown that Thr177 phosphorylation of human Prdx6 increases its PLA(2) activity, especially at neutral pH. Therefore, we investigated if human Erk2 kinase could also phosphorylate homologous Thr residues in non-mammalian Prdx6 proteins. We observed phosphorylation of the conserved Thr in three out of the five non-mammalian Prdx enzymes by mass spectrometry. In the case of the mitochondrial Prdx6 from A. fumigatus (AfPrxC), we also observed phosphorylation by western blot, and as a consequence, the PLA(2) activity was increased in acidic and neutral conditions by the human Erk2 kinase treatment. The possible physiological meanings of these PLA(2) activities described open new fields for future research. (AU)

• FAPESP's process: 16/12248-5 - Identification and characterization of acidic Ca2+-independent phospholipase A2 (aiPLA2) activity of three peroxiredoxins from human opportunistic pathogen Aspergillus fumigatus
• Grantee: Renata Bannitz Fernandes
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate (Direct)
• FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
• Grantee: Ohara Augusto
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC