The chemistry of cell signaling by reactive oxygen and nitrogen species and 4-hydroxynonenal

Abstract

During the past several years, major advances have been made in understanding how reactive oxygen species (ROS) and nitrogen species (RNS) participate in signal transduction. Identification of the specific targets and the chemical reactions involved still remains to be resolved with many of the signaling pathways in which the involvement of reactive species has been determined. Our understanding is that ROS and RNS have second messenger roles. While cysteine residues in the thiolate (ionized) form found in several classes of signaling proteins can be specific targets for reaction with H 2 O 2 and RNS, better understanding of the chemistry, particularly kinetics, suggests that for many signaling events in which ROS and RNS participate, enzymatic catalysis is more likely to be involved than non-enzymatic reaction. Due to increased interest in how oxidation products, particularly lipid peroxidation products, also are involved with signaling, a review of signaling by 4-hydroxy-2-nonenal (HNE) is included. This article focuses on the chemistry of signaling by ROS, RNS, and HNE and will describe reactions with selected target proteins as representatives of the mechanisms rather attempt to comprehensively review the many signaling pathways in which the reactive species are involved. Keywords signaling; glutathione; thioredoxin; oxidants; reactive oxygen species; thiols; peroxide; nitric oxide; peroxynitrite; 4-hydroxynonenal; cysteine; hydrogen peroxide; protein tyrosine phosphatase; reactive nitrogen species; eNOS; iNOS; nNOS; soluble guanylate cyclase; cGMP; tyrosine nitration; fatty acid nitration; NO-heme; NO-metal complexes; nitrite; protein kinase C; ERK; JNK; p38MAPK; tyrosine kinase receptors; calcium OVERVIEW OF SIGNALING BY REACTIVE SPECIESUnderstanding of the roles of reactive oxygen species (ROS), reactive nitrogen species (RNS) and the lipid peroxidation product, 4-hydroxy-2-nonenal (HNE) in signaling has evolved rapidly during the last decade. This has been markedly helped by identification of the specific targets in signaling pathways. In previous reviews, we defined how ROS, H 2 O 2 in particular,

Cilostazol Attenuates 4-hydroxynonenal-enhanced CD36 Expression on Murine Macrophages via Inhibition of NADPH Oxidase-derived Reactive Oxygen Species Production

“…Consistent with other reports showing that lipid peroxidation products, including HNE and other reactive aldehydes, stimulated ROS formation in various types of cells (Knobel et al, 2006;Lee et al, 2006;Raza and John, 2006;Forman et al, 2008), a significant increase in ROS generation by HNE was observed in J774A.1 macrophages.…”

Protein oxidation inhibits NO-mediated signaling pathway for synaptic plasticity

“…Oxidizing agents including endogenous ROS also modify cysteine residues and exert its action on proteins (Ansari et al, 2006;Forman et al, 2008;Mikkelsen and Wardman, 2003;Suzuki et al, 2010). Therefore, NO and oxidizing agents competitively share cysteine residues to exert their action, and it is highly possible that oxidizing agents affect S-nitrosylation mediated signaling pathways essential 6 for the potentiation of PF synapse and impair or occlude the potentiation.…”

Myocardial and Renal Ischemia/Reperfusion Injury and Experimental Models: Review

“…16,17 Örneğin; malondialdehit, 4-hidroksi-2-hekzenal ve akrolein gibi lipit hidroperoksidaz tü-revleri kaspaz yollarını etkinleştirerek apoptozu indüklerler, ayrıca proteinlerin proteazomal degredasyona duyarlılığını artırarak, hücre sinyali bozukluğuna neden olurlar ve proteinlerin tersiyer yapısına etkiyerek işlevlerini bozarlar, aldehitler DNA zedelenmesine neden olurlar ve ısı şok proteini (heat shock protein) 72'yi değiştirerek hücre koruyucu etkisini azaltırlar. 14,[17][18][19] Dahası, hücre içi Ca 2+ artışı, hücresel pH değerinin normalleşmesi ve serbest radikallerin reperfüzyon süresince aşırı üretimi mitokondriyal permeabilite geçiş porları [mitochondrial permeability transition pores; (mPTPs)]'nın açık kalma süresini uzatarak mitokondri içeriğinin sitozole geçmesine ve mitokondriyal çöküşe neden olur; bu durum ise hücre canlılığının kaybolmasıyla sonuçlanır. 4,[20][21][22][23] ROT, yüksek derişimdeki Ca 2+ ve oksidan kimyasallar mitokondriyal permeabilite geçişini [mitochondrial permeability transition; (MPT)]'yi indüklerken; magnezyum iyonu, düşük pH değeri ve siklosporin A engeller.…”