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A 4-oxo-2(E)-nonenal-derived glutathione-adduct from 15-lipoxygenase-1-mediated oxidation of cytosolic and esterified arachidonic acid

Publication year: 2009
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 2 July 2009
Peijuan, Zhu , Wenying, Jian , Ian A., Blair

15(S)-hydroperoxy-[5Z,8Z,11Z,13E]-eicosatetraenoic acid (15(S)-HpETE) undergoes homolytic decomposition to bifunctional electrophiles such as 4-oxo-2(E)-nonenal. 4-Oxo-2(E)-nonenal reacts with glutathione to form thiadiazabicyclo-4-oxo-2(E)-nonenal-glutathione-adduct (TOG). Therefore, this endogenous glutathione-adduct can serve as a specific biomarker of lipid-hydroperoxide-mediated 4-oxo-2(E)-nonenal formation. A monocyte/macrophage cell line was generated to constitutively express human 15-lipoxygenase-1. In these cells, TOG was formed from 15(S)-HpETE-derived 4-Oxo-2(E)-nonenal in a non-linear dose-dependent manner upon arachidonic acid treatment. The lipoxygenase inhibitor, cinnamyl-3,4-dihydroxy-?-cyanocinnamate, abolished arachidonic acid-mediated TOG formation. Calcium ionophore A23187 was also used to induce the formation of 15(S)-HpETE from esterified arachidonic acid present in the membrane lipids. In the 15-lipoxygenase-1-expressing cells, calcium ionophore A23187...

Thu, 02 Jul 2009 03:07

Kinetic Feasibility of Nitroxyl (HNO) Reduction by Physiological Reductants and Biological Implications

Publication year: 2009
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 2 July 2009
Matthew I., Jackson , Tae H., Han , Laura, Serbulea , Andrew, Dutton , Eleonora, Ford , ...

Nitroxyl (HNO), the one-electron reduced and protonated congener of nitric oxide (NO), is a chemically unique species with potentially important biological activity. Although HNO-based pharmaceuticals are currently being considered for the treatment of chronic heart failure or stroke/transplant-derived ischemia, the chemical events leading to therapeutic responses are not established. The interaction of HNO with oxidants results in the well-documented conversion to NO, but HNO is expected to be readily reduced as well. Recent thermodynamic calculations predict that reduction of HNO is biologically accessible. Herein, kinetic analysis suggests that the reactions of HNO with several mechanistically distinct reductants are also biologically...

Thu, 02 Jul 2009 03:07

Melatonin inhibits cardiolipin peroxidation in mitochondria and prevents the mitochondrial permeability transition and cytochrome c release

Publication year: 2009
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 2 July 2009
Giuseppe, Petrosillo , Nicola, Moro , Francesca M., Ruggiero , Giuseppe, Paradies

Cardiolipin oxidation is emerging as an important factor in mitochondrial dysfunction as well as in the initial phase of the apoptotic process. We have previously shown that exogenously added peroxidized cardiolipin, sensitizes mitochondria to Ca2+-induced mitochondrial permeability transition pore (MPT) and promotes the release of cytochrome c. In the present work, the effect of intramitochondrial cardiolipin peroxidation on Ca2+-induced MPT and on the cytochrome c release from mitochondria, was studied. The effect of melatonin, a compound known to protect the mitochondria from oxidative damage, on both these two processes was also tested. Tert-butlyhydroperoxide (t-BuOOH), a lipid soluble peroxide which promotes...

Thu, 02 Jul 2009 03:07

Regulation of Nrf2-dependent gene expression by 15- deoxy-?12,14-prostaglandin J2

Publication year: 2009
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 30 June 2009
Emilia, Kansanen , Annukka M., Kivelä , Anna-Liisa, Levonen

J series of cyclopentenone prostaglandins such as 15d-PGJ2 are electrophilic lipid signaling mediators derived from non-enzymatic dehydration of PGD2, a major product of the cyclooxygenase pathway. The biological actions of 15d-PGJ2 are attributed to its ability to form covalent adducts with thiol residues within specific signaling proteins thus triggering redox sensitive cell signaling pathways. One of the signaling pathways potently activated by 15d-PGJ2 is the Keap1-Nrf2-ARE system, which has a well appreciated role in protecting cells from endogenous and exogenous stresses as well as anti-inflammatory effects. In this review, we give an overview of the mechanisms by which 15d-PGJ2 activates...

Tue, 30 Jun 2009 04:06

Nrf2 promotes neuronal cell differentiation

Publication year: 2009
Source: Free Radical Biology and Medicine, In Press, Accepted Manuscript, Available online 30 June 2009
Fei, Zhao , Tongde, Wu , Alexandria, Lau , Tao, Jiang , Zheping, Huang , ...

The transcription factor Nrf2 has emerged as a master regulator for the endogenous antioxidant response, which is critical in defending cells against environmental insults and in maintaining intracellular redox balance. However, whether Nrf2 has any role in neuronal cell differentiation is largely unknown. In this report, we have examined the effects of Nrf2 on cell differentiation using a neuroblastoma cell line, SH-SY5Y. Retinoic acid (RA) and 12-O-tetradecanoylphorbol-13-acetate (TPA), two well-studied inducers for neuronal differentiation, are able to induce Nrf2 and its target gene NAD(P)H quinone oxidoreductase 1 (NQO1) in a dose- and time- dependent manner. RA-induced Nrf2 up-regulation is accompanied...

Tue, 30 Jun 2009 04:06