Sites of inhibition of mitochondrial electron transport by rhein

Floridi, Aristide; S, Castiglione; Bíanchi, C

doi:10.1016/0006-2952(89)90226-8

Cited by 23 publications

(11 citation statements)

References 21 publications

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“…The pharmacologic inhibitor for PKC (GF109203X) was obtained from ALEXIS Biochemicals (San Diego, CA). The pharmacologic inhibitor for mitochondria complex I and NADPH oxidase diphenyleneiodium (DPI), the competitive inhibitor of mitochondria complex I (rhein) (Kean et al, 1971; Floridi et al, 1989), the inhibitor for mitochondria complex I (rotenone), and the ROS scavenger N-acetylcysteine (NAC) were purchased from Sigma. Anti-human phospho-Erk1/2 antibodies were purchased from Cell Signaling Technology, Inc. (Beverly, MA).…”

Section: Methodsmentioning

confidence: 99%

Redox‐regulation of Erk1/2‐directed phosphatase by reactive oxygen species: Role in signaling TPA‐induced growth arrest in ML‐1 cells

Traore

Sharma

Thimmulappa

et al. 2008

Journal Cellular Physiology

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Extracellular signal-regulated kinase (Erk)1/2 activity signals myeloid cell differentiation induced by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Previously, we reported that Erk1/2 activation (phosphorylation) induced by TPA required reactive oxygen species (ROS) as a second messenger. Here, we hypothesized that ROS generated in response to TPA inhibit Erk1/2-directed phosphatase activity, which leads to an increase phosphorylation of Erk1/2 to signal p21WAF1/Cip1-mediated growth arrest in ML-1 cells. Incubation of ML-1 cells with TPA resulted in a marked accumulation of phosphorylated Erk1/2, and is subsequent to H2O2 generation. Interestingly, post-TPA-treatment with N-acetylcysteine (NAC) stimulated a marked and a rapid dephosphorylation of Erk1/2, suggesting a regeneration of Erk1/2-directed phospahatase activity by NAC. ROS generation in ML-1 cells induced by TPA was suggested to occur in the mitochondrial electron transport chain (METC) based on the following observations: (i) undifferentiated ML-1 cells not only lack p67-phox and but also express a low level of p47-phox key components required for NADPH oxidase enzymatic activity, (ii) pretreatment with DPI, an inhibitor of NADH- and NADPH-dependent enzymes, or rhein, an inhibitor of complex I, blocked the ROS generation, and (iii) examination of the microarray analysis data and Western blot analysis data revealed an induction of MnSOD expression at both mRNA and protein levels in response to TPA. MnSOD is a key member of the mitochondrial defense system against mitochondrial-derived superoxide. Together, this study suggested that TPA stimulated ROS generation as a second messenger to activate Erk1/2 via a redox-mediated inhibition of Erk1/2-directed phosphatase in ML-1 cells.

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Section: Methodsmentioning

confidence: 99%

Redox‐regulation of Erk1/2‐directed phosphatase by reactive oxygen species: Role in signaling TPA‐induced growth arrest in ML‐1 cells

Traore

Sharma

Thimmulappa

et al. 2008

Journal Cellular Physiology

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“…Quinone pigments and related metabolites from microorganisms possess various biological properties including antimicrobial activity, which is often explained by the inhibition of electron transport (Taniguchi et al 1984;Haraguchi et al 1986;Floridi et al 1989) or by the uncoupling of oxidative phosphorylation (Kawai et al 1982(Kawai et al , 1984 in the respiratory chain. It is also widely accepted that the action of many quinone compounds in cells is partially or completely due to their capacity to stimulate superoxide production (Afanas'ev et al 1990).…”

Section: Introductionmentioning

confidence: 99%

Respiratory stimulation and generation of superoxide radicals in Pseudomonas aeruginosa by fungal naphthoquinones

Haraguchi

Yokoyama

Oike

et al. 1997

Archives of Microbiology

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The mechanism of action of antimicrobial naphthoquinones from the fungus Fusarium was studied by using Pseudomonas aeruginosa. Bostricoidin, methyl ether fusarubin, and fusarubin stimulated the oxygen consumption of bacterial cells and induced cyanide-insensitive oxygen consumption. These activities of the tested compounds were also observed in bacterial membrane preparations in a dose-dependent manner. Naphthoquinones stimulated the generation of superoxide anion and hydrogen peroxide. The naphthoquinone effectively acted as the electron acceptors for bacterial diaphorase, which could explain the antibacterial activity of Fusarium naphthoquinones since electron acceptors lead to the stimulation of respiratory activity and the generation of oxygen radical species.

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“…Thus the additional factor of influence of qui nones on the system of glutathione metabolism is dem onstrated, which may attribute to their toxici ty to some extent. This is especially interesting for naturally occurring oxyquinones which activity is accociated with the inhibition o f m itochondrial electron transport chain (rhein, G -2N ) [11,13] or redox cycling (javanicin) [10]. It seems that qui nones being uncompetitive inhibitors for N A D PH bind to the interface dom ain o f enzyme which is distinct from NA D P(H ) and GSSG-binding sites [8].…”

Section: Resultsmentioning

confidence: 99%

“…Evidently, oxyquinones being competitive inhibitors for N A D PH bind at its binding site in oxidized gluta thione reductase. It is known that certain oxyqui nones bind to NAD(P)H-binding centers of flavo proteins [13,14], The mixed character of inhibition o f rhein (Fig. 2) and javanicin may be explained by their binding both at the NADP(H)-binding site and at the interface domain.…”

Section: Resultsmentioning

confidence: 99%