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| 1 | NADPH debt drives redox bankruptcy:SLC7A11/xCT-mediated cystine uptake as a double-edged sword in cellular redox regulation显示文摘Cystine/glutamate antiporter solute carrier family 7 member 11(SLC7A11;also known as xCT)plays a key role in antioxidant defense by mediating cystine uptake,promoting glutathione synthesis,and maintaining cell survival under oxidative stress conditions.Recent studies showed that,to prevent toxic buildup of highly insoluble cystine inside cells,cancer cells with high expression of SLC7A11(SLC7A11high)are forced to quickly reduce cystine to more soluble cysteine,which requires substantial NADPH supply from the glucose-pentose phosphate pathway(PPP)route,thereby inducing glucose-and PPP-dependency in SLC7A11high cancer cells.Limiting glucose supply to SLC7A11high cancer cells results in significant NADPH“debt”,redox“bankruptcy”,and subsequent cell death.This review summarizes our current understanding of NADPH-generating and-consuming pathways,discusses the opposing role of SLC7A11 in protecting cells from oxidative stresseinduced cell death such as ferroptosis but promoting glucose starvationeinduced cell death,and proposes the concept that SLC7A11-mediated cystine uptake acts as a double-edged sword in cellular redox regulation.A detailed understanding of SLC7A11 in redox biology may identify metabolic vulnerabilities in SLC7A11high cancer for therapeutic targeting. | Xiaoguang Liu Yilei Zhang Li Zhuang Kellen Olszewski Boyi Gan | 2021 | Genes & Diseases2021，8，6： | 7 |
| 2 | Modulation of tau phosphorylation by environmental copper显示文摘Background:The transition metal copper enhances amyloidβaggregation and neurotoxicity,and in models of concomitant amyloid and tau pathology,copper also promotes tau aggregation.Since it is not clear if the effects of environmental copper upon tau pathology are dependent on the presence of pathological amyloidβ,we tested the effects of copper overload and complexing in disease models which lack pathological amyloidβ.Methods:We used cell culture and transgenic murine models to test the effects of environmental copper on tau phosphorylation.We used oral zinc acetate as a copper lowering agent in mice and examined changes in blood and brain metals through inductively coupled plasma mass spectroscopy.Behavioral effects of copper lowering were assessed with Morris water maze and novel object recognition tasks.Changes in tau phosphorylation were examined by phosphorylation specific antibodies on Western blots.Results:In human neuroblastoma cells,excess copper promoted tau phosphorylation and a copper complexing agent,tetrathiomolybdate,attenuated tau phosphorylation.In a transgenic mouse model expressing wild type human tau,copper-lowering by oral zinc suppressed plasma and brain levels of copper,and resulted in a marked attenuation of tau phosphorylation.No significant changes in behavior were observed with copper lowering,but a trend to improved recognition of the novel object was observed in zinc acetate treated mice.Conclusions:We propose that reduction of brain copper by blocking uptake of copper from the diet may be a viable strategy for modulating tau pathology in Alzheimer’s disease.The potential benefits of this approach are tempered by the absence of a behavioral benefit and by the health risks of excessive lowering of copper. | Kellen Voss Christopher Harris Martina Ralle Megan Duffy Charles Murchison Joseph F Quinn | 2014 | Translational Neurodegeneration2014，3，1： | 3 |
| 3 | An integrative model of coupled water and solute exchange in the heart 显示文摘 | Kellen MR Bassingthwaighte JB | 2003 | Am J Physiol Heart Circ Physiol2003，285，3： | 1 |
| 4 | Increased toxin - incuced liver injury and fibrosis in interleukin -6 -deficient mice 显示文摘 | Kellen K Robert A DeAngelis | 2000 | Hepatology2000，31，1： | 1 |
| 5 | Hypertension in Sprague-Dawley rats after single or multiple challenge with DMBA显示文摘 | Kellen JA Anderson KM | 1972 | Res Commun Chem Pathol Pharmacol1972，3，1： | 1 |
| 6 | Computer-as- sisted assessment of hyoid bone motion from videofluoro- scopic swallow studies显示文摘 | Kellen PM Becker DL Reinhardt JM | 2010 | Dysphagia2010，25，： | 1 |
| 7 | Stress induced accumulation of WGA and ABA in roots of wheat seedlings显示文摘 | CAMMUE B P A BROEKAERT W F KELLENS J T C | 1989 | Plant Physiol1989，91，4： | 1 |
| 8 | Perception and Communication of Flood Risks: A Systematic Review of Empirical Research显示文摘 | Wim Kellens Teun Terpstra Philippe De Maeyer | 2012 | An International Journal2012，，： | 1 |
| 9 | Calibration of capacitance probe sensors in a saline silty clay soil显示文摘 | Kelleners T J Soppe R W Ayars J E | 2004 | Soil SciSocAm J2004，68，： | 1 |
| 10 | Contribution of trans-fatty acids from vegetable oils and margarines to the Belgian diet显示文摘 | Greyt W Radanyi O Kellens M | 1996 | Fett/Lipid1996，98，： | 1 |
| 11 | An integrative model of coupled water and solute exchange in the heart 显示文摘 | Kellen MR Bassingthwaighte JB | 2003 | Am J Physiol Heart Circ Physiol2003，28，5： | 1 |
| 12 | Environmental im- pact reduction in discrete manufacturing: Examples for non-conventional processes 显示文摘 | Kellens K Dewulf W Lauwers B | 2013 | Procedia CIRP2013，6，： | 1 |
| 13 | Transient transcapillary exchange of water driven by osmotic forces in the heart 显示文摘 | Kellen MR Bassingthwaighte JB | 2003 | Am J Physiol Heart Circ Physiol2003，285，13： | 1 |
| 14 | Effect ofphysical refining on selected minor components in vegetable oils显示文摘 | De Greyt W F Kellens M J Huyghebaert AD | 1999 | Lipid/Fett1999，101，11： | 1 |
| 15 | Prevention of sports injury I:a systematic review of applied biomechanics and physiology outeomes显示文摘 | Kellen MeBain Ian ShrierRebecea Shultz | 2012 | Br J Sports Med2012，46，3： | 1 |
| 16 | Calibration of capacitance probe sensors in a saline silty clay soil显示文摘 | Kelleners T J Soppe R W O Ayars J E | 2004 | Soil Science Society of America Journal2004，68，5： | 1 |
| 17 | Blood cadmium may be associated with bladder carcinogenesis: The Belgian case -control study on bladder cancer 显示文摘 | Kellen E Zeegers M P Hond E D | 2007 | Cancer Detect Prev2007，31，1： | 1 |
| 18 | Transient transcapillary exchange of water driven by osmotic forces in the heart显示文摘 | Kellen MR Bassingthwaighte JB | 2003 | Am J Physiol Heart Circ Physiol2003，285，3： | 1 |
| 19 | Effect of two nonoccluded viruses of amyelois transitella on larvae of cadrafigulilella and ephestia elutella (Lepidoptera:Pyralidae) in laboratory tests显示文摘 | Kellen W R Hoffmann D F | 1987 | Environmental Entomology1987，16，3： | 1 |
| 20 | Stress induced accumulation of wheat germ agglutinin and abscisic acid in roots of wheat seedlings显示文摘 | Cammue Bruno Broekaertw Willem Kellens Jan | 1989 | Plant Physiology1989，91，： | 1 |
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