Perturbation of redox balance after thioredoxin reductase deficiency interrupts autophagy-lysosomal degradation pathway and enhances cell death in nutritionally stressed SH-SY5Y cells

Nagakannan, Pandian; Iqbal, Mohamed Ariff; Yeung, Albert K. W.; Thliveris, James A.; Rastegar, Mojgan; Ghavami, Saeid; Eftekharpour, Eftekhar

doi:10.1016/j.freeradbiomed.2016.09.026

Cited by 38 publications

(26 citation statements)

References 60 publications

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“…Gold compounds, especially auranofin ( 1 ), are highly effective at inhibiting the function of the mitochondrial thioredoxin system, which comprises thioredoxin (Trx), thioredoxin reductase (TrxR) and NADPH as the key components [ 165 , 166 , 167 ]. Under normal conditions, the thioredoxin system participates in cellular processes, such as the reduction of protein disulphide, facilitates the production and removal of ROS, e.g., H 2 O 2 , and regulates the transcription factors required for cell proliferation [ 168 , 169 , 170 ]. The reduction of Trx by TrxR is an essential event for cancer cells to synthesise transcription factors required for their proliferation, survival, invasion and metastasis [ 170 ].…”

Section: Gold Compounds and Their Biological Mechanisms Of Actionmentioning

confidence: 99%

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

2018

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A new era of metal-based drugs started in the 1960s, heralded by the discovery of potent platinum-based complexes, commencing with cisplatin [(H3N)2PtCl2], which are effective anti-cancer chemotherapeutic drugs. While clinical applications of gold-based drugs largely relate to the treatment of rheumatoid arthritis, attention has turned to the investigation of the efficacy of gold(I) and gold(III) compounds for anti-cancer applications. This review article provides an account of the latest research conducted during the last decade or so on the development of gold compounds and their potential activities against several cancers as well as a summary of possible mechanisms of action/biological targets. The promising activities and increasing knowledge of gold-based drug metabolism ensures that continued efforts will be made to develop gold-based anti-cancer agents.

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Section: Gold Compounds and Their Biological Mechanisms Of Actionmentioning

confidence: 99%

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

2018

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“…This is quickly converted to H 2 O 2 that will then activate the downstream signaling by activation of tyrosine kinases and concurrent inactivation of phosphatases to optimize the effect of the extracellular factors [ 32 ]. Our lab has recently shown that the level of ROS can affect cell-signaling machinery between cell survival and cell death [ 33 ]; therefore, the levels of ROS must be tightly regulated. We further showed that oxidative modification of methionine residues in cathepsin L may be responsible for a balance between the protective autophagy and apoptosis [ 34 ].…”

Section: Role Of Ros In Cell Signaling: a Basic Understandingmentioning

confidence: 99%

Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

Iqbal

Eftekharpour

2017

Stem Cells International

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In 1990s, reports of discovery of a small group of cells capable of proliferation and contribution to formation of new neurons in the central nervous system (CNS) reversed a century-old concept on lack of neurogenesis in the adult mammalian brain. These cells are found in all stages of human life and contribute to normal cellular turnover of the CNS. Therefore, the identity of regulating factors that affect their proliferation and differentiation is a highly noteworthy issue for basic scientists and their clinician counterparts for therapeutic purposes. The cues for such control are embedded in developmental and environmental signaling through a highly regulated tempo-spatial expression of specific transcription factors. Novel findings indicate the importance of reactive oxygen species (ROS) in the regulation of this signaling system. The elusive nature of ROS signaling in many vital processes from cell proliferation to cell death creates a complex literature in this field. Here, we discuss the emerging thoughts on the importance of redox regulation of proliferation and maintenance in mammalian neural stem and progenitor cells under physiological and pathological conditions. The current knowledge on ROS-mediated changes in redox-sensitive proteins that govern the molecular mechanisms in proliferation and differentiation of these cells is reviewed.

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“…For instance, a similar situation has been observed in sepsis, in which the rate of autophagic clearance of damaged organelles was outpaced by the extent of sustained insult to hepatocytes . Conversely, it is possible that the increase in oxidative stress impairs autophagic activity in cells …”

Section: Autophagy In the Ageing Heartmentioning

confidence: 69%

“…37 Conversely, it is possible that the increase in oxidative stress impairs autophagic activity in cells. 38,39 Metabolic and hormonal changes accompanying ageing may contribute to lower levels of autophagy. Age-related activation of autophagy suppressors, in addition to inhibition of autophagy activators, may also play a role here.…”

Section: Autophagy In the Ageing Heartmentioning

confidence: 99%

Autophagy—A key pathway for cardiac health and longevity

Woodall

Gustafsson

2018

Acta Physiologica

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As average life expectancy continues to rise in the developed world, age-associated pathologies are increasing in prevalence. The hallmarks of cardiac ageing include cardiomyocyte loss, fibrosis and hypertrophy, all of which contribute to an increased incidence of cardiac disease. At the molecular level, cellular ageing is characterized by increased ROS production, mitochondrial dysfunction and the accumulation of damaged proteins and organelles. Cardiomyocytes and other senescent cell types rely upon autophagy, a lysosome-mediated degradation pathway, to remove potentially toxic protein aggregates and damaged organelles from the cellular milieu. However, increasing lines of evidence point to an age-associated decrease in cardiomyocyte autophagy, with predictably negative consequences for cardiac function and health. Conversely, stimulation of autophagy has been shown to improve cellular health and cardiac function and to increase lifespan in numerous model organisms. Clearly, autophagy represents a critical pathway for cellular vitality, as well as a promising therapeutic target for the treatment of age-related cardiac pathologies. In this review, we will discuss the mechanism of autophagy and its regulation in the cell, the role of autophagy in the ageing heart, and how the autophagy pathway might be targeted to improve cardiac health.

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Perturbation of redox balance after thioredoxin reductase deficiency interrupts autophagy-lysosomal degradation pathway and enhances cell death in nutritionally stressed SH-SY5Y cells

Cited by 38 publications

References 60 publications

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

Gold-Based Medicine: A Paradigm Shift in Anti-Cancer Therapy?

Regulatory Role of Redox Balance in Determination of Neural Precursor Cell Fate

Autophagy—A key pathway for cardiac health and longevity

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