Mitochondrial superoxide production during oxalate-mediated oxidative stress in renal epithelial cells

Purpose. We aim to figure out the effect of metallothioneins on iodide excess induced oxidative stress in the thyroid.Methods. Eight-week-old MT-I/II knockout (MT-I/II KO) mice and background-matched wild-type (WT) mice were used. Mitochondrial superoxide production and peroxiredoxin (Prx) 3 expression were measured.Results. In in vitro study, more significant increases in mitochondrial superoxide production and Prx 3 expression were detected in the MT-I/II KO groups. In in vivo study, significantly higher concentrations of urinary iodine level were detected in MT-I/II KO mice in 100 HI group. Compared to the NI group, there was no significant difference existing in serum thyroid hormones level in either groups (P>0.05), while the mitochondrial superoxide production was significantly increased in 100 HI groups with significantly increased LDH activity and decreased relative cell viability. Compared to WT mice, more significant changes were detected in MT-I/II KO mice in 100 HI groups. No significant differences were detected between the NI group and 10 HI group in both the MT-I/II KO and WT mice groups (P>0.05).Conclusions. Iodide excess in a thyroid without MT I/II protection may result in strong mitochondrial oxidative stress, which further leads to the damage of thyrocytes.

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Suppression of HGF receptor gene expression by oxidative stress is mediated through the interplay between Sp1 and Egr-1

AJP Renal Physiology ◽

10.1152/ajprenal.00426.2002 ◽

2003 ◽

Vol 284 (6) ◽

pp. F1216-F1225 ◽

Cited By ~ 32

Author(s):

Xianghong Zhang ◽

Youhua Liu

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Collecting Duct ◽

Receptor Gene ◽

Ectopic Expression ◽

Transcriptional Activator ◽

Physical Interaction ◽

Nucleotide Position ◽

Renal Epithelial Cells ◽

Cis Acting

Hepatocyte growth factor (HGF) receptor, the product of the c-metprotooncogene, is transcriptionally regulated by a wide variety of cytokines as well as extracellular environmental cues. In this report, we demonstrate that c-met expression was significantly suppressed by oxidative stress. Treatment of mouse renal inner medullary collecting duct epithelial cells with 0.5 mM H2O2inhibited c-met mRNA and protein expression, which was concomitant with induction of Egr-1 transcription factor. Ectopic expression of Egr-1 in renal epithelial cells markedly inhibited endogenous c-met expression in a dose-dependent fashion, suggesting a causative effect of Egr-1 in mediating c-met suppression. The cis-acting element responsible for H2O2-induced c-met inhibition was localized at nucleotide position −223 to −68 of c-met promoter, in which reside an imperfect Egr-1 and three Sp1-binding sites. Egr-1 markedly suppressed c-met promoter activity but did not directly bind to its cis-acting element in the c-met gene. Induction of Egr-1 by oxidative stress attenuated the binding of Sp1 to its cognate sites, but it did not affect Sp1 abundance in renal epithelial cells. Immunoprecipitation uncovered that Egr-1 physically interacted with Sp1 by forming the Sp1/Egr-1 complex, which presumably resulted in a decreased availability of unbound Sp1 as a transcriptional activator for the c-met gene. Thus it appears that inhibition of c-met expression by oxidative stress is mediated by the interplay between Sp1 and Egr-1 transcription factors. Our findings reveal a novel transcriptional regulatory mechanism by which Egr-1 sequesters Sp1 as a transcriptional activator of c-met via physical interaction.

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PROTECTION OF BCL-XL TRANSFECTED RENAL EPITHELIAL CELLS DURING OXIDATIVE STRESS

Nephrology ◽

10.1046/j.1440-1797.2002.00007-1-132.x ◽

2002 ◽

Vol 7 (1) ◽

pp. A132-A132

Author(s):

Cuttle L ◽

Pat Bk ◽

Endre Zh ◽

Gobe GC

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Renal Epithelial Cells

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Heat-shock protein 25 ameliorates calcium oxalate crystal-mediated oxidative stress in renal epithelial cells

BJU International ◽

10.1111/j.1464-410x.2006.06478.x ◽

2006 ◽

Vol 98 (5) ◽

pp. 1094-1099 ◽

Cited By ~ 7

Author(s):

Amit B. Patel ◽

William G. Robertson ◽

Simon Choong ◽

John S. Hothersall

Keyword(s):

Oxidative Stress ◽

Heat Shock ◽

Epithelial Cells ◽

Heat Shock Protein ◽

Calcium Oxalate ◽

Calcium Oxalate Crystal ◽

Renal Epithelial Cells

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Plant-Derived Natural Biomolecule Picein Attenuates Menadione Induced Oxidative Stress on Neuroblastoma Cell Mitochondria

Antioxidants ◽

10.3390/antiox9060552 ◽

2020 ◽

Vol 9 (6) ◽

pp. 552 ◽

Cited By ~ 2

Author(s):

Kavindra Kumar Kesari ◽

Anupam Dhasmana ◽

Shruti Shandilya ◽

Neeraj Prabhakar ◽

Ahmed Shaukat ◽

...

Keyword(s):

Oxidative Stress ◽

Neuroblastoma Cell ◽

Water Extract ◽

Subsequent Treatment ◽

Hot Water ◽

Superoxide Production ◽

Mitochondrial Activity ◽

Mitochondrial Superoxide ◽

In Silico Studies

Several bioactive compounds are in use for the treatment of neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease. Historically, willow (salix sp.) bark has been an important source of salisylic acid and other natural compounds with anti-inflammatory, antipyretic and analgesic properties. Among these, picein isolated from hot water extract of willow bark, has been found to act as a natural secondary metabolite antioxidant. The aim of this study was to investigate the unrevealed pharmacological action of picein. In silico studies were utilized to direct the investigation towards the neuroprotection abilities of picein. Our in vitro studies demonstrate the neuroprotective properties of picein by blocking the oxidative stress effects, induced by free radical generator 2-methyl-1,4-naphthoquinone (menadione, MQ), in neuroblastoma SH-SY5Y cells. Several oxidative stress-related parameters were evaluated to measure the protection for mitochondrial integrity, such as mitochondrial superoxide production, mitochondrial activity (MTT), reactive oxygen species (ROS) and live-cell imaging. A significant increase in the ROS level and mitochondrial superoxide production were measured after MQ treatment, however, a subsequent treatment with picein was able to mitigate this effect by decreasing their levels. Additionally, the mitochondrial activity was significantly decreased by MQ exposure, but a follow-up treatment with picein recovered the normal metabolic activity. In conclusion, the presented results demonstrate that picein can significantly reduce the level of MQ-induced oxidative stress on mitochondria, and thereby plays a role as a potent neuroprotectant.

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Asymmetric superoxide release inside and outside the mitochondria in skeletal muscle under conditions of aging and disuse

Journal of Applied Physiology ◽

10.1152/japplphysiol.00174.2010 ◽

2010 ◽

Vol 109 (4) ◽

pp. 1133-1139 ◽

Cited By ~ 11

Author(s):

Xin Xu ◽

Chiao-nan (Joyce) Chen ◽

Edgar A. Arriaga ◽

LaDora V. Thompson

Keyword(s):

Oxidative Stress ◽

Skeletal Muscle ◽

Oxidative Damage ◽

Superoxide Production ◽

Type I ◽

Electrophoretic Method ◽

Specific Product ◽

Mitochondrial Superoxide ◽

The Matrix ◽

Superoxide Release

Superoxide released from mitochondria forms reactive oxygen species that can cause severe oxidative damage and have been associated with aging- and disuse-induced muscle dysfunction. Superoxide is released to both the exterior and the matrix of mitochondria, where oxidative damage is not necessarily the same. This complicates determining the role of mitochondrial superoxide in eliciting oxidative stress in skeletal muscle. A newly developed capillary electrophoretic method analyzes hydroxytriphenylphosphonium ethidium, a superoxide-specific product of triphenylphosphonium hydroethidine, released to outside the mitochondria (supernatant) and retained in the matrix (pellet). In this study, we investigated the mitochondrial superoxide production of soleus (type I) and semimembranosus (type II) muscles of Fischer 344 rats affected by aging (13 vs. 26 mo) and disuse (hindlimb unloading). In agreement with previous studies, overall superoxide production increased with aging and disuse. On the other hand, the new experimental method revealed that superoxide production outside the mitochondria of the soleus does not show a significant age-related increase. Another observation was that the superoxide production increase in the matrix occurs earlier (7 days of disuse) compared with the outside mitochondria (14 days of disuse) in both muscle types. These findings indicate that superoxide release is complex as it occurs asymmetrically at both sides of the mitochondrial inner membrane, and that such release has muscle type and temporal specificity. These findings are important to refine current concepts on oxidative stress associated with muscle aging and disuse.

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