Giovanni E. Mann

King's College London

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Richard Siow

King's College London

Sarah J. Chapple

King's College London

Tetsuro Ishii

University of Tsukuba

Jeremy D. Pearson

King's College London

Anwar R. Baydoun

De Montfort University

Tatiana M.C. Brunini

Universidade do Estado do Rio de Janeiro

Paul Fraser

King's College London

D. L. Yudilevich

King's College London

J. C. Ellory

University of Oxford

Salil Srivastava

Guy's and St Thomas' NHS Foundation Trust

Cooperative Institutions

King's College London

254

Petra Christian University

103

British Heart Foundation

University of Liverpool

University of Manchester

Universidade do Estado do Rio de Janeiro

University of Birmingham

Physiological Society

University College London

Rotherham General Hospital

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Discrimination between citrulline and arginine transport in activated murine macrophages: inefficient synthesis of NO from recycling of citrulline to arginine

British Journal of Pharmacology (1994)

Anwar R. Baydoun Richard Bogle Jeremy D. Pearson Giovanni E. Mann

The kinetics, specificity, pH‐ and Na + ‐dependency of l ‐citrulline transport were examined in unstimulated and lipopolysaccharide (LPS)‐activated murine macrophage J774 cells. The dependency of nitric oxide production on extracellular arginine or citrulline was investigated in cells activated with LPS (1 μg ml −1 ) for 24 h. In unstimulated J774 cells, transport of citrulline was saturable ( K t = 0.16 m m and V max = 32 pmol μg −1 protein min −1 ), pH‐insensitive and partially Na + ‐dependent. In contrast to arginine, transport of citrulline was unchanged in LPS‐activated (1 μg ml −1 , 24 h) cells. Kinetic inhibition experiments revealed that arginine was a relatively poor inhibitor of citrulline transport, whilst citrulline was a more potent inhibitor ( K i = 3.4 m m ) of arginine transport but only in the presence of extracellular Na + . Neutral amino acids inhibited citrulline transport ( K i = 0.2–0.3 m m ), but were poor inhibitors of arginine transport. Activated J774 cells did not release nitrite in the absence of exogenous arginine. Addition of citrulline (0.01 − 10 m m ), in the absence of exogenous arginine, could only partially restore the ability of cells to synthesize nitrite, which was abolished by 100 μ m N G ‐nitro‐ l ‐arginine methyl ester or N G ‐iminoethyl‐ l ‐ornithine. Intracellular metabolism of l ‐[ 14 C]‐citrulline to l ‐[ 14 C]‐arginine was detected in unstimulated J774 cells and was increased further in cells activated with LPS and interferon‐γ. We conclude that J774 macrophage cells transport citrulline via a saturable but nonselective neutral carrier which is insensitive to induction by LPS. In contrast, transport of arginine via the cationic amino acid system y + is induced in J774 cells activated with LPS. Our findings also confirm that citrulline can be recycled to arginine in activated J774 macrophage cells. Although this pathway provides a mechanism for enhanced arginine generation required for NO production under conditions of limited arginine availability, it cannot sustain maximal rates of NO synthesis.

10.1111/j.1476-5381.1994.tb13099.x

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Citations (69)

Secretagogue-induced changes in system A amino acid transport in the rat exocrine pancreas: stimulation of 2-methylaminoisobutyric acid efflux by carbachol

Biochimica et Biophysica Acta (BBA) - Biomembranes (1988)

Philip S. Norman Giovanni E. Mann

Secretagogue

Washout

10.1016/0005-2736(88)90388-4

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Citations (10)

Ionic dependence of amino-acid transport in the exocrine pancreatic epithelium: Calcium dependence of insulin action

The Journal of Membrane Biology (1987)

Philip S. Norman Giovanni E. Mann

10.1007/bf01869241

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Citations (27)

Importance of physiological oxygen levels for endothelial redox signaling using Hyper 7

Free Radical Biology and Medicine (2023)

Hamza Yusuf Altun Fan Yang Giovanni E. Mann Emrah Eroğlu

10.1016/j.freeradbiomed.2023.10.018

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Stress Activated MAP Kinases and Cyclin-Dependent Kinase 5 Mediate Nuclear Translocation of Nrf2 via Hsp90α-Pin1-Dynein Motor Transport Machinery

Antioxidants (2023)

Tetsuro Ishii Eiji Warabi Giovanni E. Mann

Non-lethal low levels of oxidative stress leads to rapid activation of the transcription factor nuclear factor-E2-related factor 2 (Nrf2), which upregulates the expression of genes important for detoxification, glutathione synthesis, and defense against oxidative damage. Stress-activated MAP kinases p38, ERK, and JNK cooperate in the efficient nuclear accumulation of Nrf2 in a cell-type-dependent manner. Activation of p38 induces membrane trafficking of a glutathione sensor neutral sphingomyelinase 2, which generates ceramide upon depletion of cellular glutathione. We previously proposed that caveolin-1 in lipid rafts provides a signaling hub for the phosphorylation of Nrf2 by ceramide-activated PKCζ and casein kinase 2 to stabilize Nrf2 and mask a nuclear export signal. We further propose a mechanism of facilitated Nrf2 nuclear translocation by ERK and JNK. ERK and JNK phosphorylation of Nrf2 induces the association of prolyl cis/trans isomerase Pin1, which specifically recognizes phosphorylated serine or threonine immediately preceding a proline residue. Pin1-induced structural changes allow importin-α5 to associate with Nrf2. Pin1 is a co-chaperone of Hsp90α and mediates the association of the Nrf2-Pin1-Hsp90α complex with the dynein motor complex, which is involved in transporting the signaling complex to the nucleus along microtubules. In addition to ERK and JNK, cyclin-dependent kinase 5 could phosphorylate Nrf2 and mediate the transport of Nrf2 to the nucleus via the Pin1-Hsp90α system. Some other ERK target proteins, such as pyruvate kinase M2 and hypoxia-inducible transcription factor-1, are also transported to the nucleus via the Pin1-Hsp90α system to modulate gene expression and energy metabolism. Notably, as malignant tumors often express enhanced Pin1-Hsp90α signaling pathways, this provides a potential therapeutic target for tumors.

10.3390/antiox12020274

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Citations (7)

Environmental estrogenic pollutants induce acute vascular relaxation by inhibiting L‐type Ca ²⁺ channels in smooth muscle cells

The FASEB Journal (1998)

Dietrich O. Ruehlmann Joern R. Steinert Miguel A. Valverde Ron Jacob Giovanni E. Mann

There is an ongoing scientific debate concerning the potential threat of environmental estrogenic pollutants to animal and human health (1–5). Pollutants including the detergents 4-octylphenol and p-nonylphenol and chlorinated insecticides have recently been reported to modulate sexual differentiation by interacting with nuclear steroid receptors (6–8). So far, the focus has been on reproductive organs, but sex steroids have far more widespread actions. The lower incidence of cardiovascular disease in women has been attributed to estrogens (9–14), yet no information is available on the vascular actions of environmental estrogenic pollutants. In the present study we have investigated the effects of acute exposure to 17β-estradiol, the antiestrogen ICI 182,780, and estrogenic pollutants on coronary vascular tone as well as on intracellular Ca2+ levels ([Ca2+]i) and Ca2+ and K+ channel activity in vascular smooth muscle cells. We report here that 4-octylphenol, p-nonylphenol, o.p′-DDT, and the antiestrogen ICI 182,780 inhibit L-type Ca2+ channels in vascular smooth muscle cells and evoke a rapid and endothelium-independent relaxation of the coronary vasculature similar to that induced by 17β-estradiol. Thus, inhibition of Ca2+ influx via L-type Ca2+ channels in vascular smooth muscle cells may explain the acute, nongenomic vasodilator actions of environmental estrogenic pollutants.

Antiestrogen

Nonylphenol

10.1096/fasebj.12.7.613

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Citations (147)

Redox and lipidomic analysis of human brain microvascular endothelial cells (hCMEC/D3) adapted to physiological oxygen levels

Free Radical Biology and Medicine (2024)

Fan Yang Simon Daniel Emrah Eroğlu Dag Aarsland Richard Siow

10.1016/j.freeradbiomed.2024.04.174

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Citations (0)

Chronic myelomonocytic leukemia (CMML) in childhood. (Abstract)

C. Niemeyer Maurizio Aricò Andrea Biondi Giuseppe Basso A. Cantù Rajnoldi

Chronic myelomonocytic leukemia

Childhood leukemia

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Citations (1)

Dietary soy modulates endothelium-dependent relaxation in aged male rats: Increased agonist-induced endothelium-derived hyperpolarising factor and basal nitric oxide activity

Free Radical Biology and Medicine (2006)

Greg A. Knock Katharina Mahn Giovanni E. Mann Jeremy Ward Philip I. Aaronson

Apamin

Mesenteric arteries

10.1016/j.freeradbiomed.2006.05.017

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Citations (14)

Dietary Isoflavones: Cardiovascular Actions and Activation of Cellular Signaling Pathways

Richard Siow Giovanni E. Mann

This chapter contains sections titled: Introduction Vascular Actions of Dietary Isoflavones in Vivo Nitric Oxide Synthesis as a Vascular Target for Dietary Isoflavones Activation of Cellular Signaling Pathways and Antioxidant Defense Genes by Isoflavones Conclusions and Future Perspectives Acknowledgments References

Cell Signaling

10.1002/9780470531792.ch12

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Citations (1)