• The Korea Journal of Herbology
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• v.30 no.6
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• pp.7-15
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• 2015

Objectives : Rosa laevigata Michx. has been used for the treatment of renal disease in traditional Korean medicine. In this study, we investigated cytoprotective effect of R. laevigata water extract (RLE) against oxidative stress induced by arachidonic acid (AA) + iron.Methods : To evaluate the protective effects of RLE against AA + iron-induced oxidative stress in HepG2 cell, cell viability and changes on apoptosis-related proteins were assessed by MTT and immunoblot analyses. The effects of RLE on reduced glutathione level, production of reactive oxygen species and mitochondrial membrane potential were also monitored. Furthermore, to verify underlying molecular mechanism, NF-E2-related factor 2 (Nrf2) was examined by immunoblot analysis. Additionally, Nrf2 transactivation and its downstream target genes expression were also determined by reporter gene and realtime RT-PCR analyses.Results : RLE pretreatment (30-300 μg/ml) prevented cells from AA + iron-mediated cell death in a concentration dependent manner. In addition, 100 μg/ml RLE inhibited AA + iron-induced glutathione depletion, reactive oxygen species production and mitochondrial dysfunction. RLE accumulated nuclear Nrf2 and also transactivated Nrf2, which was evidenced by antioxidant response element- and glutathione S-transferase A2-driven luciferase activities and mRNA level of glutamate-cysteine ligase catalytic subunit, NAD(P)H:quinone oxidoreductase 1 and sestrin 2. Moreover, protective effect of RLE against AA + iron was abolished in Nrf2 knockout cells.Conclusions : These results indicate that RLE has the ability to protect hepatocyte against oxidative stress through Nrf2 activation.

• Journal of Life Science
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• v.34 no.1
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• pp.68-77
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• 2024

Airborne particulate matter (PM) is an environmentally hazardous pollutant that originates from various sources. PM is comprised of solid particles and liquid droplets of diverse composition and size. Hazardous chemical compositions of PM include elemental and organic carbon, organic compounds, biological compounds and metals. Upon acute and chronic PM exposure, toxic contaminants enter and accumulate within physiological systems and prompt cell structure changes accompanied with intracellular endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, inflammation, lipid accumulation, and cell cycle arrest. Ultimately, these cellular response leads to the development of key characteristics of aging. In addition, PM internalization enhances autophagy reflux and lysosomal dysfunction, which is involved in cell aging. Previous studies have emphasized a positive association between PM and increased mortality or decreased lifespan, although these are evidenced mostly by observational studies. Direct evidence of the link between PM and aging is still limited. This review evaluates the evidence from not only observational studies but also in vitro and in vivo evidence of PM on aging progression and age-related diseases development. This evidence is based on age-associated cellular changes including endoplasmic reticulum stress, mitochondrial dysfunction, oxidative stress, inflammation, adipose accumulation, autophagy, which strengthen the association between PM exposure and aging. Understanding the underlying cellular responses under PM may allow for the development of new therapeutic targets for PM-induced aging.

• Molecules and Cells
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• v.26 no.5
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• pp.427-435
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• 2008

In this review, we discuss the genes and the related signal pathways that regulate aging and longevity by reviewing recent findings of genetic longevity models in rodents in reference to findings with lower organisms. We also paid special attention to the genes and signals mediating the effects of calorie restriction (CR), a powerful intervention that slows the aging process and extends the lifespan in a range of organisms. An evolutionary view emphasizes the roles of nutrient-sensing and neuroendocrine adaptation to food shortage as the mechanisms underlying the effects of CR. Genetic and non-genetic interventions without CR suggest a role for single or combined hormonal signals that partly mediate the effect of CR. Longevity genes fall into two categories, genes relevant to nutrient-sensing systems and those associated with mitochondrial function or redox regulation. In mammals, disrupted or reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 signaling robustly favors longevity. CR also suppresses the GH-IGF-1 axis, indicating the importance of this signal pathway. Surprisingly, there are very few longevity models to evaluate the enhanced anti-oxidative mechanism, while there is substantial evidence supporting the oxidative stress and damage theory of aging. Either increased or reduced mitochondrial function may extend the lifespan. The role of redox regulation and mitochondrial function in CR remains to be elucidated.

• Journal of Plant Biotechnology
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• v.44 no.2
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• pp.115-124
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• 2017

Cytoplasmic male sterility (CMS) is a maternally inherited trait leading to loss of the ability to produce fertile pollen and is extensively used in hybrid crop breeding. Ogura-CMS was originally generated by insertion of orf138 upstream of atp8 in the radish mitochondrial genome and transferred to Brassica crops for hybrid breeding. Gene expression changes by dysfunctional mitochondria in Ogura-CMS result in pollen developmental defects, but little is known about gene expression patterns in vegetative tissue. To examine the interaction between nuclear and organellar regulation of gene expression, microarray and subsequent gene expression experiments were conducted with leaves of $F_1$ hybrid Chinese cabbage derived from self-incompatible (SI) or Ogura-CMS parents (Brassica rapa ssp. pekinensis). Out of 24,000 genes deposited on a KBGP24K microarray, 66 genes were up-regulated and 26 genes were down-regulated by over 2.5 fold in the CMS leaves. Up-regulated genes included stress-response genes and mitochondrial protein genes, while genes for ascorbic acid biosynthesis and thylakoid proteins were down-regulated. Most of the major component genes for light reactions of photosynthesis were highly expressed in leaves of both SI and CMS plants, but most of the corresponding proteins were found to be greatly reduced in leaves of CMS plants, indicating posttranscriptional regulation. Reduction in thylakoid proteins and chlorophylls led to reduction in photosynthetic efficiency and chlorosis of Ogura-CMS at low temperatures. This research provides a foundation for studying chloroplast function regulated by mitochondrial signal and for using organelle genome introgression in molecular breeding.

• Interdisciplinary Bio Central
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• v.5 no.4
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• pp.9.1-9.7
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• 2013

Introduction: Tumor necrosis factor receptor-associated protein 1 (TRAP1) is a mitochondrial heat shock protein (HSP), which belongs to HSP90 family. It plays important roles in regulating mitochondrial integrity, protecting against oxidative stress, and inhibiting cell death. Recent studies suggest that TRAP1 is linked to mitochondria and its metabolism. In this study, we established TRAP1 transgenic mice and performed partial hepatectomy (PH) on wild-type (WT) and TRAP1 transgenic mice to investigate the function of TRAP1 during liver regeneration. Results and Discussion: We found that TRAP1 was highly expressed in liver as well as kidney. In addition, liver regeneration slightly decreased together with increased fatty liver and inflammation at 72 hr after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. These results suggest that TRAP1 plays a critical role in liver energy balance by regulating lipid accumulation during liver regeneration. Conclusions and Prospects: To our knowledge, we reported, for the first time, that liver regeneration slightly reduced together with increased fat accumulations after PH in TRAP1 transgenic mice compared with WT control group mice. Concomitantly, we observed decreased levels of p38 protein in TRAP1 transgenic mice compared with WT control group mice. Overexpression of TRAP1 might affect liver regeneration via disturbing mitochondrial function leading to fatty liver in vivo.

• Advances in Traditional Medicine
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• v.10 no.4
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• pp.239-253
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• 2010

Coenzyme $Q_{10}$ ($CoQ_{10}$, or ubiquinone) is an electron carrier of the mitochondrial respiratory chain (electron transport chain) with antioxidant properties. In view of the involvement of $CoQ_{10}$ in oxidative phosphorylation and cellular antioxidant protection a deficiency in this quinone would be expected to contribute to disease pathophysiology by causing a failure in energy metabolism and antioxidant status. Indeed, a deficit in $CoQ_{10}$ status has been determined in a number of neuromuscular and neurodegenerative disorders. Primary disorders of $CoQ_{10}$ biosynthesis are potentially treatable conditions and therefore a high degree of clinical awareness about this condition is essential. A secondary loss of $CoQ_{10}$ status following HMG-CoA reductase inhibitor (statins) treatment has been implicated in the pathophysiology of the myotoxicity associated with this pharmacotherapy. $CoQ_{10}$ and its analogue, idebenone, have been widely used in the treatment of neurodegenerative and neuromuscular disorders. These compounds could potentially play a role in the treatment of mitochondrial disorders, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, Friedreich's ataxia, and other conditions which have been linked to mitochondrial dysfunction. This article reviews the physiological roles of $CoQ_{10}$, as well as the rationale and the role in clinical practice of $CoQ_{10}$ supplementation in different neurological diseases, from primary $CoQ_{10}$ deficiency to neurodegenerative disorders. These will help in future for treatment of patients suffering from neurodegenerative disease.

• Journal of Radiation Protection and Research
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• v.34 no.2
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• pp.49-54
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• 2009

Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with $^{137}Cs$ $\gamma$-rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and $H_2O_2$-treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and $H_2O_2$-treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.1
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• pp.58-64
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• 2020

This present study was conducted to investigate protective effect of discontinuous Percoll gradient containing alpha-linolenic acid (ALA) before freezing process on viability, acrosome damage, mitochondrial activity, and oxidative stress of frozen-thawed boar spermatozoa. The separation of spermatozoa by discontinuous Percoll gradient was performed by different concentration of Percoll solution (45/90%) containing ALA combined with bovine serum albumin (BSA), and collected sperm in each Percoll layer was cryopreserved. To evaluate viability, acrosome damage, mitochondrial activity, and reactive oxygen species (ROS) level of frozen-thawed sperm, flow cytometry was used. Morphological abnormalities were observed under light microscope. In results, viability of sperm from 90% Percoll layer was higher than control and 45% Percoll group (p < 0.05). Separated sperm in 90% Percoll layer had lower acrosome damage and morphological abnormalities than control as well as viability, whereas 45% Percoll group was higher (p < 0.05). Similar with acrosome damage and abnormalities, mitochondrial activity was slightly enhanced and the population of live sperm with high ROS level was decreased by 90% Percoll separation, however, there was no significant difference. Supplementation of 3 ng/mL ALA into Percoll solution increased sperm viability and decreased population of live sperm with high ROS compared to control (p < 0.05). In conclusion, discontinuous Percoll gradient before freezing process could improve efficiency of cryopreservation of boar sperm through selection of sperm with high freezing resistance, and supplement of ALA during Percoll gradient might contribute suppression of ROS generation via stabilizing of plasma membrane during cryopreservation.

• Korean Journal of Pharmacognosy
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• v.49 no.3
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• pp.231-239
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• 2018

Parkinson's disease (PD), one of common neurodegenerative diseases, is caused by the death of dopaminergic neurons in the substantia nigra pars compacta. The loss of dopaminergic neurons in PD is associated with oxidative stress and mitochondrial dysfunction. Hyperoside (quercetin 3-O-${\beta}$-D-galactopyranoside) was reported to have protective properties against oxidative stress by reducing intracellular reactive oxygen species (ROS) and increasing antioxidant enzyme activity. In this study, we examined the neuroprotective effect of hyperoside against 1-methyl-4-phenyl pyridinium ($MPP^+$)-induced cell model of PD and the underlying molecular mechanisms. Hyperoside significantly decreased $MPP^+$-induced cell death, accompanied by a reduction in poly ADP-ribose polymerase (PARP) cleavage. Furthermore, it attenuated $MPP^+$-induced intracellular ROS and disruption of mitochondrial membrane potential (MMP), with the reduction of Bax/Bcl-2 ratio. Moreover, hyperoside significantly increased the phosphorylation of Akt, but it has no effects on $GSK3{\beta}$ and MAPKs. Pharmacological inhibitor of PI3K/Akt abolished the cytoprotective effects of hyperoside against $MPP^+$. Taken together, these results demonstrate that hyperoside significantly attenuates $MPP^+$-induced neurotoxicity through PI3K/Akt signaling pathways in SH-SY5Y cells. Our findings suggest that hyperoside might be one of the potential candidates for the treatment of PD.

• Journal of Microbiology and Biotechnology
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• v.31 no.6
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• pp.867-874
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• 2021

Epalrestat (EPS) is a brain penetrant aldose reductase inhibitor, an approved drug currently used for the treatment of diabetic neuropathy. At near-plasma concentration, EPS induces glutathione biosynthesis, which in turn reduces oxidative stress in the neuronal cells. In this study, we found that EPS reduces neurodegeneration by inhibiting reactive oxygen species (ROS)-induced oxidative injury, mitochondrial membrane damage, apoptosis and tauopathy. EPS treatment up to 50 µM did not show any toxic effect on SH-SY5Y cell line (neuroblastoma cells). However, we observed toxic effect at a concentration of 100 µM and above. At 50 µM concentration, EPS showed better antioxidant activity against H₂O₂ (100 µM)-induced cytotoxicity, ROS formation and mitochondrial membrane damage in retinoic acid-differentiated SH-SY5Y cell line. Furthermore, our study revealed that 50 µM of EPS concentration reduced the glycogen synthase kinase-3 β (GSK3-β) expression and total tau protein level in H₂O₂ (100 µM)-treated cells. Findings from this study confirms the therapeutic efficacy of EPS on regulating Alzheimer's disease (AD) by regulating GSK3-β and total tau proteins phosphorylation, which helped to restore the cellular viability. This process could also reduce toxic fibrillary tangle formation and disease progression of AD. Therefore, it is our view that an optimal concentration of EPS therapy could decrease AD pathology by reducing tau phosphorylation through regulating the expression level of GSK3-β.