Antioxidant Effects of Stereoisomers of N-Acetylcysteine (NAC), L-NAC and D-NAC, on Angiotensin II-Stimulated MAP Kinase Activation and Vascular Smooth Muscle Cell Proliferation

Kyaw, Moe H.; Yoshizumi, Masanori; Tsuchiya, Koichiro; Izawa, Yuki; Kanematsu, Yasuhisa; Fujita, Yoshiko; Ali, Nermin; Ishizawa, Keisuke; Yamauchi, Aiko; Takahashi, Toshiaki

doi:10.1254/jphs.sc0040061

Cited by 18 publications

(15 citation statements)

References 16 publications

(19 reference statements)

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“…In additional experiments, the metabolically inactive stereoisomer of NAC, D-NAC, was found to produce similar effects to those observed for NAC, including an increase in eosinophil glutathione. Although unexpected, this result is consistent with similar findings for D-NAC in cultured neuronal [28] and vascular smooth muscle [29] cells, and is likely to be due to the reduction of extracellular cystine to cysteine, which is then efficiently transported into cells [28]. PDTC, a nonthiol antioxidant [18], which was shown not to increase eosinophil glutathione, also caused pro-apoptotic effects on cytokineexposed eosinophils, similar to those elicited by NAC.…”

Section: Discussionsupporting

confidence: 86%

Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis

Martínez‐Losa¹,

Cortijo²,

Juan³

et al. 2007

European Respiratory Journal

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Eosinophils are oxidant-sensitive cells considered relevant in allergic inflammation. The present study aimed to examine the effects of the antioxidant N-acetyl-L-cysteine (NAC) on constitutive and cytokine-delayed apoptosis in human isolated eosinophils.Human eosinophils were purified from the blood of healthy donors by a magnetic separation system. Apoptosis and cellular glutathione were assessed by cytofluorometric analysis and nuclear factor (NF)-kB binding activity assessed by electrophoresis mobility shift assay.The rate of spontaneous apoptosis of human eosinophils after 24 h culture, as assessed by annexin-V-positive staining, was mean¡sem 48.2¡1.4%, n55. Granulocyte-macrophage colonystimulating factor (GM-CSF; 10 ng?mL -1

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Section: Discussionsupporting

confidence: 86%

Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis

Martínez‐Losa¹,

Cortijo²,

Juan³

et al. 2007

European Respiratory Journal

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“…S-phase cells showed an intermediate redox state (Conour et al, 2004). Our laboratory, as well as others, has shown modulating intracellular redox state using NAC inhibits proliferation in mouse embryonic fibroblasts, hepatic stellate cells and vascular smooth muscle cells (Kim et al, 2001;Menon et al, 2003;Kyaw et al, 2004). These results further support the hypothesis that intracellular redox state is a critical regulator of cell cycle progression.…”

Section: Introductionsupporting

confidence: 70%

A redox cycle within the cell cycle: ring in the old with the new

2006

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In recent years, the intracellular oxidation-reduction (redox) state has gained increasing attention as a critical mediator of cell signaling, gene expression changes and proliferation. This review discusses the evidence for a redox cycle (i.e., fluctuation in the cellular redox state) regulating the cell cycle. The presence of redox-sensitive motifs (cysteine residues, metal co-factors in kinases and phosphatases) in several cell cycle regulatory proteins indicate periodic oscillations in intracellular redox state could play a central role in regulating progression from G 0 /G 1 to S to G 2 and M cell cycle phases. Fluctuations in the intracellular redox state during cell cycle progression could represent a fundamental mechanism linking oxidative metabolic processes to cell cycle regulatory processes. Proliferative disorders are central to a variety of human pathophysiological conditions thought to involve oxidative stress. Therefore, a more complete understanding of redox control of the cell cycle could provide a biochemical rationale for manipulating aberrant cell proliferation.

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“…Both NAC and TEMPO-9-AC have antioxidant activities that may contribute to protection against oxidative stress. NAC scavenges free radicals and augments intracellular levels of glutathione (15). TEMPO-AC-9 is a nitroxide that acts as an antioxidant detoxifying ferryl heme species, facilitating heme-mediated catalytic removal of H 2 O 2 , trapping carbon-centered radicals and terminating radical chain reactions.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Rat Petrosal Ganglion Neurons During Development Using Organotypic Slices

Kwak

Gauda

2006

Pediatr Res

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Hyperoxia, during development in rats, results in hypoxic chemosensitivity ablation, carotid body hypoplasia, and reduced chemoafferents. We hypothesized that hyperoxia increases reactive oxygen species (ROS) in cell bodies of chemoafferents. Organotypic slices of petrosal-nodose ganglia from rats at day of life (DOL) 5-6 and 17-18 were exposed to 8%, 21%, or 95% O 2 for 4 h in the presence or absence of the ROS-sensitive fluorescent indicator, CM-H 2 DCFDA, and propidium iodide was used to determine the relationship between cell death and oxygen tension. In tissue slices from DOL 5-6 rats, fluorescence intensity was 182.5 Ϯ 2.9 for hypoxia, 217.5 Ϯ 3.3 for normoxia, and 336.6 Ϯ 3.8 for hyperoxia, (mean Ϯ SEM, p Ͻ 0.001, ANOVA). Normoxia increased ROS levels by 19.2% from hypoxia (p Ͻ 0.01) with a further increase of 54.8% from normoxia to hyperoxia (p Ͻ 0.001). In tissue slices from DOL 17-18 rats, ROS levels increased with increasing oxygen tension but were less than in younger animals (p Ͻ 0.01, ANOVA). The antioxidants, NAC and TEMPO-9-AC, attenuated ROS levels and cell death. Electron microscopy demonstrated that hyperoxia damages the ultrastructure within petrosal ganglion neurons. Hyperoxic-induced increased levels of ROS in petrosal ganglion neurons may contribute to loss of hypoxic chemosensitivity during early postnatal development. N umerous studies in mammalian species support a role for peripheral arterial chemoreceptors in stabilizing ventilation at a critical period during early postnatal development, which establishes rhythmogenesis that is sustained throughout life (1,2). The components of the peripheral arterial chemoreceptors are found within the carotid body that is located in the bifurcation of the carotid artery and consists of three major neuronal components that include: 1) type I chemosensory cells, also known as glomus cells, which contain neurotransmitters and autoreceptors; 2) type II cells, which are similar to supportive glial cells; and 3) chemoafferent nerve fibers from the carotid sinus nerve, a branch of the IX cranial nerve, with cell bodies in the petrosal ganglion (PG) (3,4).Exposure to chronic hyperoxia, during the first weeks of postnatal development, depresses ventilatory responses to subsequent acute hypoxia in newborn animals and in premature infants (5-7). Hyperoxic exposure in newborn rat pups is cytotoxic to peripheral arterial chemoreceptors as evidenced by hypoplasia of the carotid body and a 41% reduction in the number of chemoafferent neurons (8). The mechanisms leading to cytotoxic changes in the carotid body and the reduction in chemoreflexes after hyperoxicexposure during early postnatal development are unknown. In other model systems, hyperoxia is associated with increased production of ROS, including superoxide, hydroxyl radical, and hydrogen peroxide, which can contribute to cellular damage via lipid peroxidation, enzyme inactivation, and protein and nucleic acid oxidation, resulting in apoptosis or necrosis (9). Using a novel ex vivo organotypic s...

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Antioxidant Effects of Stereoisomers of N-Acetylcysteine (NAC), L-NAC and D-NAC, on Angiotensin II-Stimulated MAP Kinase Activation and Vascular Smooth Muscle Cell Proliferation

Cited by 18 publications

References 16 publications

Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis

Modulatory effects of N-acetyl-L-cysteine on human eosinophil apoptosis

A redox cycle within the cell cycle: ring in the old with the new

The Effect of Hyperoxia on Reactive Oxygen Species (ROS) in Rat Petrosal Ganglion Neurons During Development Using Organotypic Slices

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