Harmful Effects of Inorganic Mercury Exposure on Kidney Cells: Mitochondrial Dynamics Disorder and Excessive Oxidative Stress

Exercise and antioxidants have health benefits that improve cognitive impairment and may act synergistically. In this study, we examined the effects of treadmill exercise (TE) and mitochondria-targeted antioxidant mitoquinone (MitoQ), individually or combined, on learning and memory, mitochondrial dynamics, NADPH oxidase activity, and neuroinflammation and antioxidant activity in the hippocampus of D-galactose-induced aging rats. TE alone and TE combined with MitoQ in aging rats reduced mitochondrial fission factors (Drp1, Fis1) and increased mitochondrial fusion factors (Mfn1, Mfn2, Opa1). These groups also exhibited improved NADPH oxidase activity and antioxidant activity (SOD-2, catalase). TE or MitoQ alone decreased neuroinflammatory response (COX-2, TNF-α), but the suppression was greater with their combination. In addition, aging-increased neuroinflammation in the dentate gyrus was decreased in TE but not MitoQ treatment. Learning and memory tests showed that, contrarily, MitoQ alone demonstrated some similar effects to TE but not a definitive improvement. In conclusion, this study demonstrated that MitoQ exerted some positive effects on aging when used as an isolated treatment, but TE had a more effective role on cognitive impairment, oxidative stress, inflammation, and mitochondria dysfunction. Our findings suggest that the combination of TE and MitoQ exerted no synergistic effects and indicated regular exercise should be the first priority in neuroprotection of age-related cognitive decline.

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Syntaxin-17-Dependent Mitochondrial Dynamics is Essential for Protection Against Oxidative-Stress-Induced Apoptosis

Antioxidants ◽

10.3390/antiox8110522 ◽

2019 ◽

Vol 8 (11) ◽

pp. 522 ◽

Cited By ~ 4

Author(s):

Wang ◽

Xiao ◽

Huang ◽

Liu

Keyword(s):

Oxidative Stress ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Autophagic Flux ◽

Wild Type ◽

Dual Roles ◽

Defective Mutant ◽

U2os Cells ◽

Induced Apoptosis

In this study, cell death induced by the oxidant tert-butylhydroperoxide (tBH) was observed in U2OS cells; this phenotype was rescued by Syntaxin 17 (STX17) knockout (KO) but the mechanism is unknown. STX17 plays dual roles in autophagosome–lysosome fusion and mitochondrial fission. However, the contribution of the two functions of STX17 to apoptosis has not been extensively studied. Here, we sought to dissect the dual roles of STX17 in oxidative-stress-induced apoptosis by taking advantage of STX17 knockout cells and an autophagosome–lysosome fusion defective mutant of STX17. We generated STX17 knockout U2OS cells using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system and the STX17 knockout cells were reconstituted with wild-type STX17 and its autophagosome–lysosome fusion defective mutant. Autophagy was assessed by autophagic flux assay, Monomer red fluorescent protein (mRFP)–GFP–LC3 assay and protease protection assay. Golgi, endoplasmic reticulum (ER)/ER–Golgi intermediate compartment (ERGIC) and mitochondrial dynamics were examined by staining the different indicator proteins. Apoptosis was evaluated by caspase cleavage assay. The general reactive oxygen species (ROS) were detected by flow cytometry. In STX17 complete knockout cells, sealed autophagosomes were efficiently formed but their fusion with lysosomes was less defective. The fusion defect was rescued by wild-type STX17 but not the autophagosome–lysosome fusion defective mutant. No obvious defects in Golgi, ERGIC or ER dynamics were observed. Mitochondria were significantly elongated, supporting a role of STX17 in mitochondria fission and the elongation caused by STX17 KO was reversed by the autophagosome–lysosome fusion defective mutant. The clearance of protein aggregation was compromised, correlating with the autophagy defect but not with mitochondrial dynamics. This study revealed a mixed role of STX17 in autophagy, mitochondrial dynamics and oxidative stress response. STX17 knockout cells were highly resistant to oxidative stress, largely due to the function of STX17 in mitochondrial fission rather than autophagy.

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Inorganic mercury exposure, mercury-copper interaction, and DMPS treatment in rats.

Environmental Health Perspectives ◽

10.1289/ehp.94102s3305 ◽

1994 ◽

Vol 102 (suppl 3) ◽

pp. 305-307 ◽

Cited By ~ 8

Author(s):

M Blanusa ◽

L Prester ◽

S Radić ◽

B Kargacin

Keyword(s):

Inorganic Mercury ◽

Mercury Exposure

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Mercury Exposure and Endothelial Dysfunction

International Journal of Toxicology ◽

10.1177/1091581815589766 ◽

2015 ◽

Vol 34 (4) ◽

pp. 300-307 ◽

Cited By ~ 13

Author(s):

Swati Omanwar ◽

M. Fahim

Keyword(s):

Oxidative Stress ◽

Nitric Oxide ◽

Endothelial Dysfunction ◽

Vascular Endothelium ◽

Circulatory System ◽

Vital Role ◽

Mercury Exposure ◽

And Function ◽

The Impact ◽

And Oxidative Stress

Vascular endothelium plays a vital role in the organization and function of the blood vessel and maintains homeostasis of the circulatory system and normal arterial function. Functional disruption of the endothelium is recognized as the beginning event that triggers the development of consequent cardiovascular disease (CVD) including atherosclerosis and coronary heart disease. There is a growing data associating mercury exposure with endothelial dysfunction and higher risk of CVD. This review explores and evaluates the impact of mercury exposure on CVD and endothelial function, highlighting the interplay of nitric oxide and oxidative stress.

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Inorganic Mercury Exposure, Mercury-Copper Interaction, and DMPS Treatment in Rats

Environmental Health Perspectives ◽

10.2307/3431808 ◽

1994 ◽

Vol 102 ◽

pp. 305 ◽

Cited By ~ 1

Author(s):

Maja Blanusa ◽

Ljerka Prester ◽

Snjezana Radic ◽

Biserka Kargacin

Keyword(s):

Inorganic Mercury ◽

Mercury Exposure

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Oxidative Stress, Antioxidant Status and DNA Damage in a Mercury Exposure Workers

British Journal of Pharmacology and Toxicology ◽

10.19026/bjpt.4.5367 ◽

2013 ◽

Vol 4 (3) ◽

pp. 80-88 ◽

Cited By ~ 7

Author(s):

Hasan F. Al-azzawie ◽

Akram Umran ◽

Nadhem H. Hyader

Keyword(s):

Oxidative Stress ◽

Dna Damage ◽

Antioxidant Status ◽

Mercury Exposure

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Cudrania tricuspidata Root Extract Prevents Methylglyoxal-Induced Inflammation and Oxidative Stress via Regulation of the PKC-NOX4 Pathway in Human Kidney Cells

Oxidative Medicine and Cellular Longevity ◽

10.1155/2021/5511881 ◽

2021 ◽

Vol 2021 ◽

pp. 1-13

Author(s):

Donghee Kim ◽

Jayeon Cheon ◽

Haelim Yoon ◽

Hee-Sook Jun

Keyword(s):

Oxidative Stress ◽

Protein Kinase ◽

Antioxidant Enzyme ◽

Root Extract ◽

Kidney Cells ◽

Nuclear Factor ◽

Ros Production ◽

Cudrania Tricuspidata ◽

Pkc Activation ◽

And Oxidative Stress

Diabetic nephropathy is a microvascular complication induced by diabetes, and methylglyoxal (MGO) is a reactive carbonyl species causing oxidative stress that contributes to the induction of inflammatory response in kidney cells. Cudrania tricuspidata (CT), cultivated in Northeast Asia, has been used as traditional medicine for treating various diseases, including neuritis, liver damage, and cancer. In this study, we determined whether a CT root extract (CTRE) can prevent MGO-induced reactive oxygen species (ROS) production and inflammation and assessed underlying mechanisms using a kidney epithelial cell line, HK-2. We observed that CTRE inhibited MGO-induced ROS production. Additionally, CTRE ameliorated the activation of MGO-induced inflammatory signaling pathways such as p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK), and c-JUN N-terminal kinase (JNK). Consistent with these results, expressions of p-nuclear factor-kappa B (NFκB) and inflammatory cytokines, tumor necrosis factor-α, interleukin- (IL-) 1β, and IL-6, were decreased when compared with MGO-only exposed HK-2 cells. CTRE alleviated the MGO-induced decrease in nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and antioxidant enzyme mRNA expressions. MGO induced the expression of NADPH oxidase 4 (NOX4); CTRE pretreatment inhibited this induction. Further studies revealed that the NOX4 expression was inhibited owing to the suppression of MGO-induced protein kinase C (PKC) activation following CTRE treatment. Collectively, our data suggest that CTRE attenuates MGO-induced inflammation and oxidative stress via inhibition of PKC activation and NOX4 expression, as well as upregulating the Nrf2-antioxidant enzyme pathway in HK-2 cells.

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MITOL deletion in the brain impairs mitochondrial structure and ER tethering leading to oxidative stress

Life Science Alliance ◽

10.26508/lsa.201900308 ◽

2019 ◽

Vol 2 (4) ◽

pp. e201900308 ◽

Cited By ~ 7

Author(s):

Shun Nagashima ◽

Keisuke Takeda ◽

Nobuhiko Ohno ◽

Satoshi Ishido ◽

Motohide Aoki ◽

...

Keyword(s):

Oxidative Stress ◽

Microglial Activation ◽

Developmental Disorders ◽

Inflammatory Diseases ◽

Mitochondrial Dynamics ◽

Mitochondrial Fission ◽

Three Dimensional ◽

Abnormal Behavior ◽

Mitochondrial Abnormalities

Mitochondrial abnormalities are associated with developmental disorders, although a causal relationship remains largely unknown. Here, we report that increased oxidative stress in neurons by deletion of mitochondrial ubiquitin ligase MITOL causes a potential neuroinflammation including aberrant astrogliosis and microglial activation, indicating that mitochondrial abnormalities might confer a risk for inflammatory diseases in brain such as psychiatric disorders. A role of MITOL in both mitochondrial dynamics and ER-mitochondria tethering prompted us to characterize three-dimensional structures of mitochondria in vivo. In MITOL-deficient neurons, we observed a significant reduction in the ER-mitochondria contact sites, which might lead to perturbation of phospholipids transfer, consequently reduce cardiolipin biogenesis. We also found that branched large mitochondria disappeared by deletion of MITOL. These morphological abnormalities of mitochondria resulted in enhanced oxidative stress in brain, which led to astrogliosis and microglial activation partly causing abnormal behavior. In conclusion, the reduced ER-mitochondria tethering and excessive mitochondrial fission may trigger neuroinflammation through oxidative stress.

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