Hydrogen sulfide increases copper-dependent neurotoxicity <i>via</i> intracellular copper accumulation

Goto, N; Hara, Hirokazu; Kondo, Mao; Yasuda, Naomi; Kamiya, Tetsuro; Okuda, K; Adachi, Tetsuo

doi:10.1039/d0mt00015a

Cited by 17 publications

(9 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mitochondria are not only the major producer of cellular ROS but also a target (42). It has been demonstrated that CuSO 4 exposure can cause mitochondrial dysfunction in neuroblastoma SH-SY5Y cells, and human hepatoma (HepG2) cells (43,44). In the present study, CuSO 4 exposure caused visible mitochondrial damage, characterized by swollen and ruptured mitochondria and disappearance of cristae.…”

Section: Figure 7 |supporting

confidence: 50%

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

View full text Add to dashboard Cite

Copper overload is an established cause of nephrotoxicity, but the precise molecular mechanism remains unknown. Our study aimed to investigate the molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity and the protective effect of the natural compound quercetin using a mouse model. Mice were orally administered CuSO4 only (200 mg/kg per day), or co-administered CuSO4 (200 mg/kg per day) plus quercetin (25, 50, or 100 mg/kg per day), or quercetin only (100 mg/kg per day), or vehicle for 28 days. The blood and kidneys were collected for the examination of serum biomarkers, oxidative stress biomarkers, changes in histopathology and gene and protein expression. Our results show that quercetin supplementation attenuates CuSO4-induced renal dysfunction and tubular necrosis in a dose-dependent manner. Quercetin supplementation at 50 and 100 mg/kg significantly attenuated CuSO4-induced oxidative damage. Quercetin supplementation also inhibited the activities of caspases-9 and−3, and the expression of p53 and Bax mRNAs. Furthermore, quercetin supplementation markedly activated the expression of Nrf2 and HO-1 mRNAs, but inhibited the expression of NF-κB, IL-1β, IL-6, and TNF-α mRNAs. In conclusion, our results revealed that quercetin supplementation could inhibit CuSO4-induced nephrotoxicity in mice via the inhibition of mitochondrial apoptotic and NF-κB pathways and the activation of Nrf2/HO-1 pathway. Our study highlights quercetin as a potential candidate in treating copper overload-induced nephrotoxicity.

show abstract

Section: Figure 7 |supporting

confidence: 50%

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

View full text Add to dashboard Cite

show abstract

“…5 B). This has previously also been shown in human neuroblastoma cells [ 74 ]. The observed effects on SEPSECS mRNA expression, GPX4 protein expression and on GPX and TXNRD activity were successfully reversed by chelator treatment and are thus Cu specific ( Fig.…”

Section: Discussionsupporting

confidence: 80%

Copper interferes with selenoprotein synthesis and activity

et al. 2020

View full text Add to dashboard Cite

Selenium and copper are essential trace elements for humans, needed for the biosynthesis of enzymes contributing to redox homeostasis and redox-dependent signaling pathways. Selenium is incorporated as selenocysteine into the active site of redox-relevant selenoproteins including glutathione peroxidases (GPX) and thioredoxin reductases (TXNRD). Copper-dependent enzymes mediate electron transfer and other redox reactions. As selenoprotein expression can be modulated e.g. by H 2 O 2 , we tested the hypothesis that copper status affects selenoprotein expression. To this end, hepatocarcinoma HepG2 cells and mice were exposed to a variable copper and selenium supply in a physiologically relevant concentration range, and transcript and protein expression as well as GPX and TXNRD activities were compared. Copper suppressed selenoprotein mRNA levels of GPX1 and SELENOW, downregulated GPX and TXNRD activities and decreased UGA recoding efficiency in reporter cells. The interfering effects were successfully suppressed by applying the copper chelators bathocuproinedisulfonic acid or tetrathiomolybdate. In mice, a decreased copper supply moderately decreased the copper status and negatively affected hepatic TXNRD activity. We conclude that there is a hitherto unknown interrelationship between copper and selenium status, and that copper negatively affects selenoprotein expression and activity most probably via limiting UGA recoding. This interference may be of physiological relevance during aging, where a particular shift in the selenium to copper ratio has been reported. An increased concentration of copper in face of a downregulated selenoprotein expression may synergize and negatively affect the cellular redox homeostasis contributing to disease processes.

show abstract

“…72 Hydrogen sulfide can trap 64 Cu at very low levels 73 or regulate copper export systems in Mycobacterium tuberculosis 74 and in human neuroblastoma cells. 75 S-Adenosylhomocysteine hydrolase, one of the key enzymes in the metabolism of thiol-containing amino acids, was found to bind appreciable amounts of copper in mouse livers 76 and its expression is regulated by copper availability in mice. 77 To what extent is modulation of cellular copper accumulation by L-cysteine important in vivo?…”

Section: Discussionmentioning

confidence: 99%

l-Cysteine-mediated modulation of copper trafficking in prostate cancer cells: an in vitro and in vivo investigation with 64Cu and 64Cu-PET

et al. 2020

View full text Add to dashboard Cite

show abstract

Hydrogen sulfide increases copper-dependent neurotoxicity via intracellular copper accumulation

Abstract: Copper (Cu) is an essential trace element and acts as a redox cofactor for many enzymes; however, excess Cu is toxic to cells.

Cited by 17 publications

References 33 publications

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

Copper interferes with selenoprotein synthesis and activity

l-Cysteine-mediated modulation of copper trafficking in prostate cancer cells: an in vitro and in vivo investigation with 64Cu and 64Cu-PET

Contact Info

Product

Resources

About