Nrf2 promotes breast cancer cell migration via up‐regulation of G6PD/HIF‐1α/Notch1 axis DOI Creative Commons
Hongsheng Zhang, Zhongguo Zhang, Guangyuan Du

et al.

Journal of Cellular and Molecular Medicine, Journal Year: 2019, Volume and Issue: 23(5), P. 3451 - 3463

Published: Feb. 26, 2019

Abstract Abnormal metabolism of tumour cells is closely related to the occurrence and development breast cancer, during which expression NF‐E2‐related factor 2 (Nrf2) great significance. Metastatic cancer one most common causes death worldwide; however, molecular mechanism underlying metastasis remains unknown. In this study, we found that overexpression Nrf2 promoted proliferation migration cancers cells. Inhibition Kelch‐like ECH‐associated protein 1 (Keap1) reduced glucose‐6‐phosphate dehydrogenase (G6PD) transketolase pentose phosphate pathway, knockdown Keap1 had opposite effects. Our results further showed G6PD Hypoxia‐inducing 1α (HIF‐1α) in MCF‐7 MDA‐MB‐231 Overexpression up‐regulated Notch1 via G6PD/HIF‐1α pathway. Notch signalling pathway affected by affecting its downstream gene HES‐1, regulated EMT The suggest a potential target for treatment targeting may provide promising strategy Nrf2‐driven metastasis.

Language: Английский

The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism DOI
Gerta Hoxhaj, Brendan D. Manning

Nature reviews. Cancer, Journal Year: 2019, Volume and Issue: 20(2), P. 74 - 88

Published: Nov. 4, 2019

Language: Английский

Citations

1521
Exercise-induced oxidative stress: Friend or foe? DOI Creative Commons
Scott K. Powers, Rafael Deminice, Mustafa Ozdemir

et al.

Journal of sport and health science/Journal of Sport and Health Science, Journal Year: 2020, Volume and Issue: 9(5), P. 415 - 425

Published: May 4, 2020

The first report demonstrating that prolonged endurance exercise promotes oxidative stress in humans was published more than 4 decades ago. Since this discovery, many ensuing investigations have corroborated the fact muscular increases production of reactive oxygen species (ROS) and results numerous tissues including blood skeletal muscles. Although several may contribute to exercise-induced ROS production, it is predicted contractions stimulate active muscle fibers a primary source during exercise. This contraction-induced generation associated with (1) oxidant damage (e.g., increased protein oxidation lipid peroxidation), (2) accelerated fatigue, (3) activation biochemical signaling pathways adaptation contracting fibers. While our understanding has advanced rapidly last decades, questions remain about whether are beneficial or harmful health. review addresses issue by discussing site(s) detailing health consequences production.

Language: Английский

Citations

463
Nrf2 and Ferroptosis: A New Research Direction for Neurodegenerative Diseases DOI Creative Commons
Xiaohua Song,

Dingxin Long

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: April 21, 2020

Ferroptosis is a kind of regulated cell death (RCD) caused by the redox state disorder intracellular microenvironment controlled glutathione peroxidase 4 (GPX4), which inhibited iron chelators and lipophilic antioxidants. In addition to classical regulatory mechanisms, new factors for ferroptosis have been discovered in recent years, such as P53 pathway, ATF3/4 Beclin 1 (BECN1) some non-coding RNA. closely related cancer treatment, neurodegenerative diseases, ischemia-reperfusion organ, neurotoxicity, other particular, field diseases treatment has aroused people's interest. The nuclear factor E2 2 (Nrf2/NFE2L2) proved play key role neurodegeneration disease regulation. promotes progression while expression Nrf2 its target genes (Ho-1, Nqo-1, Trx) declined with aging, therefore, there still insufficient evidence networks diseases. this review, we will provide brief overview well an emphasis on mechanism regulating ferroptosis. We also highlight during process investigate theoretical basis further research relationship between treatment.

Language: Английский

Citations

435
The multifaceted role of reactive oxygen species in tumorigenesis DOI
Anuradha Kirtonia, Gautam Sethi, Manoj Garg

et al.

Cellular and Molecular Life Sciences, Journal Year: 2020, Volume and Issue: 77(22), P. 4459 - 4483

Published: May 1, 2020

Language: Английский

Citations

392
Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut DOI Creative Commons
Alexandra Vaccaro,

Yosef Kaplan Dor,

Keishi Nambara

et al.

Cell, Journal Year: 2020, Volume and Issue: 181(6), P. 1307 - 1328.e15

Published: June 1, 2020

Language: Английский

Citations

378
Nrf2–ARE signaling in cellular protection: Mechanism of action and the regulatory mechanisms DOI
Pallab Shaw, Ansuman Chattopadhyay

Journal of Cellular Physiology, Journal Year: 2019, Volume and Issue: 235(4), P. 3119 - 3130

Published: Sept. 23, 2019

Abstract Oxidative stress is the increase in cellular oxidant concentration comparison to antioxidant titer. Toxic insults and many other diseased conditions are mediated through formation of such condition. Once redox equilibrium disrupted, system functions bring back cell homeostasis state. The field players cytoprotective machinery xenobiotic‐metabolizing enzymes that transcriptionally controlled by upstream regulatory pathways like Nrf2–ARE pathway AhR–XRE pathway. importance Nrf2 lies fact it activated a variety compounds has wide range inducers including metals, organic toxicants so forth. present review article aims discuss role protection also intends illuminate mechanisms control itself. This can add our knowledge how reacts survives against stressed conditions.

Language: Английский

Citations

343
Nrf2/Keap1/ARE signaling: Towards specific regulation DOI Open Access
A. V. Ulasov, Andrey A. Rosenkranz,

Georgii P. Georgiev

et al.

Life Sciences, Journal Year: 2021, Volume and Issue: 291, P. 120111 - 120111

Published: Oct. 31, 2021

Language: Английский

Citations

325
The Keap1‐Nrf2 System: A Mediator between Oxidative Stress and Aging DOI Creative Commons
Chao Yu, Jian‐Hui Xiao

Oxidative Medicine and Cellular Longevity, Journal Year: 2021, Volume and Issue: 2021(1)

Published: Jan. 1, 2021

Oxidative stress, a term that describes the imbalance between oxidants and antioxidants, leads to disruption of redox signals causes molecular damage. Increased oxidative stress from diverse sources has been implicated in most senescence‐related diseases aging itself. The Kelch‐like ECH‐associated protein 1‐ (Keap1‐) nuclear factor‐erythroid 2‐related factor 2 (Nrf2) system can be used monitor stress; Keap1‐Nrf2 is closely associated with controls transcription multiple antioxidant enzymes. Simultaneously, signaling also modulated by more complex regulatory network, including phosphoinositide 3‐kinase (PI3K)/protein kinase B (Akt), C, mitogen‐activated kinase. This review presents information on aging‐related mechanisms involving Keap1‐Nrf2. Furthermore, we highlight several major involved Nrf2 unbinding Keap1, cysteine modification Keap1 phosphorylation Nrf2, PI3K/Akt/glycogen synthase 3 β , sequestosome 1, Bach1 c ‐ Myc . Additionally, discuss direct interaction mammalian target rapamycin pathway. In summary, focus recent progress research aging, providing an empirical basis for development antiaging drugs.

Language: Английский

Citations

317
Ferroptosis is essential for diabetic cardiomyopathy and is prevented by sulforaphane via AMPK/NRF2 pathways DOI Creative Commons
Xiang Wang, Xinxin Chen, Wenqian Zhou

et al.

Acta Pharmaceutica Sinica B, Journal Year: 2021, Volume and Issue: 12(2), P. 708 - 722

Published: Oct. 19, 2021

Herein, we define the role of ferroptosis in pathogenesis diabetic cardiomyopathy (DCM) by examining expression key regulators mice with DCM and a new ex vivo model. Advanced glycation end-products (AGEs), an important pathogenic factor DCM, were found to induce engineered cardiac tissues (ECTs), as reflected through increased levels Ptgs2 lipid peroxides decreased ferritin SLC7A11 levels. Typical morphological changes cardiomyocytes observed using transmission electron microscopy. Inhibition ferrostatin-1 deferoxamine prevented AGE-induced ECT remodeling dysfunction. Ferroptosis was also evidenced heart type 2 DCM. liproxstatin-1 development diastolic dysfunction at 3 months after onset diabetes. Nuclear erythroid 2-related (NRF2) activated sulforaphane inhibited cell both AGE-treated ECTs hearts upregulating The protective effect on AMP-activated protein kinase (AMPK)-dependent. These findings suggest that plays essential DCM; prevents associated via AMPK-mediated NRF2 activation. This suggests feasible therapeutic approach clinically prevent

Language: Английский

Citations

315
Roles of Autophagy in Oxidative Stress DOI Open Access

Hyeong Rok Yun,

Yong Hwa Jo,

Ji‐Eun Kim

et al.

International Journal of Molecular Sciences, Journal Year: 2020, Volume and Issue: 21(9), P. 3289 - 3289

Published: May 6, 2020

Autophagy is a catabolic process for unnecessary or dysfunctional cytoplasmic contents by lysosomal degradation pathways. implicated in various biological processes such as programmed cell death, stress responses, elimination of damaged organelles and development. The role autophagy crucial mediator has been clarified expanded the pathological response to redox signalling. major sensor Reactive oxygen species (ROS) are highly reactive molecules that generated by-products cellular metabolism, principally mitochondria. Mitochondrial ROS (mROS) beneficial detrimental cells depending on their concentration location. mROS function messengers intracellular signalling at physiologically low level, whereas excessive production causes oxidative damage constituents thus incurs death. Hence, balance autophagy-related adaptation death important comprehend signalling-related pathogenesis. In this review, we attempt provide an overview basic mechanism context pathology.

Language: Английский

Citations

302