• Biomolecules & Therapeutics
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• 제31권1호
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• pp.97-107
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• 2023

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN). AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

• Toxicological Research
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• 제18권3호
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• pp.275-283
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• 2002

Fungal metabolite, gliotoxin is an epipolythiodioxopiperazin (ETP) class and has various roles including immunomodulatory and apoptotic effects. This study was designed to evaluate the mechanism by which gliotoxin exerts the apoptosis on human promyelocytic leukemic HL-60 cells. Herein, we demonstrated that the gliotoxin decreased the cell viability in a time-dependent manner Gliotoxin-induced cell death was confirmed us apoptosis characterized by chromatin condensation and ladder-pattern fragmentation of genomic DNA. Gliotoxin increased the catalytic activities of caspase-3 and caspase-9. Activation of caspase-3 was further confirmed by degradation of procaspase-3 and poly(ADP-ribose) polymerase (PARP) by gliotoxin in HL-60 cells. Furthermore, gliotoxin induced the changes of mitochondrial transmembrane potential (MTP). Antioxidants, including GSH and NAC, markedly inhibited apoptosis with conistent suppression of enzymatic activity of caspase-3, caspase-9, and MTP loss in gliotoxin-treated cells. Taken together, we suggest that gliotoxin function as an oxidant and ploys proapoptotic roles in HL-60 cells via activation of intrinsic caspase cascades as well as mitochondrial dysfunction.

• 대한화장품학회:학술대회논문집
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• 대한화장품학회 2003년도 IFSCC Conference Proceeding Book I
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• pp.285-290
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• 2003

Living cells are continuously subject to all sorts of stress such as ultraviolet rays on skin cells. Tests made in various laboratories show that when young fibroblasts (Le. at the beginning of their proliferate life) were repeatedly put under stress at subletal doses, they acquired a phenotype similar to Senescence Induced Prematurely by Stress (SIPS). The work presented hereafter was made on a new model of senescence induced prematurely by stress from ultraviolet Brays (UVB). The human fibroblast model was put under repeated UVB stress, causing SIPS. Several ageing biomarkers were used in order to characterise the cells that underwent stress:. an increase in the proportion of positive cells with senescence associated $\beta$-galactosidase activity (SA $\beta$-gal) measured by a specific coloration,. the proportion in the different morphological stages that fibroblasts undergo during culture visualised by microscopic observation,. the expression of genes known for overexpressing during senescence, particularly fibronectin and apolipoprotein J, measured by Real Time-PCR,. the common deletion of 4,977 bp in mitochondrial DNA, evaluated by nested PCR. Studying the variation of these 4 biomarkers, we have evaluated the protective effect of a Laminaria digitata extract (LDE) that can be used as a natural active ingredient for anti-ageing cosmetics.

• 대한화장품학회지
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• 제38권3호
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• pp.237-245
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• 2012

쿠메스트롤은 식물이 스트레스에 대항해 합성하는 phytoalexins의 일종으로, 알팔파 새싹, 클로버, 콩나물에서 일반적으로 발견된다. 본 연구에서는 쿠메스트롤의 자외선에 의해 유도되는 피부 진피세포 광노화 예방 효능에 관한 연구를 실시하였다. 쿠메스트롤 전처리는 자외선 B 조사에 의해 감소된 Sirt1 단백질 발현 및 활성과 하위 미토콘드리아 생합성 관련 유전자인 PGC-$1{\alpha}$, NRF1, TFAM의 발현 변화를 감소시켰다. 또한, ATP 및 ROS 생성량을 정상화시키고 피부 노화를 유도하는 최종당화산물 생성을 억제하였다. 이상의 결과에서 쿠메스트롤은 자외선 조사에 의해 발생하는 진피 세포 내 미토콘드리아 손상 및 이에 따른 당화 단백질 생성을 감소시킴으로써 피부 광노화 현상으로부터 보호할 수 있음을 확인하였다.

• 동의생리병리학회지
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• 제27권6호
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• pp.764-770
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• 2013

Stevia rebaudiana is a traditional herb used as a sweetener in Brazil and Paraguay as well as Korea and China. This study investigated the efficacy of Stevia rebaudiana methanol extract (SRE) to protect cells against the mitochondrial dysfunction and apoptosis in hepatocyte. To determine the effects of SRE on oxidative stress, we used the human derived hepatocyte cell line, HepG2 cell. Treatment of arachidonic acid (AA)+iron in HepG2 cells synergistically amplified cytotoxicity, as indicated by the excess reactive oxygen species (ROS) and mitochondrial permeability transition by fluorescence activated cell sorter (FACS) and immunoblot analysis. Treatment with SRE protected hepatocytes from AA+iron-induced cellular toxicity, as shown by alterations in the protein levels related with cell viability such as procaspase-3. SRE also prevented the mitochondrial dysfunction induced by AA+iron, and showed anti-oxidant effects as inhibition of $H_2O_2$ production and GSH depletion. Moreover, we measured the effects of SRE on AMP-activated protein kinase (AMPK), a key regulator in determining cell survival or death. Acetyl-CoA Carboxylase (ACC), a direct downstream target of AMPK. SRE increased phosphorylation of ACC, and prevented the inhibition of ACC phosphorylation by AA+iron. These results indicated that SRE has the ability to protect cells against AA+iron-induced $H_2O_2$ production and mitochondrial impairment, which may be mediated with AMPK-ACC pathway.

• 동의생리병리학회지
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• 제22권2호
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• pp.438-445
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• 2008

Dodam formula (Dodam) has been used for neurodegenerative disease in Oriental medicine. Dodam is capable of protecting diverse kinds of cells from damage caused by a variety of toxic stimuli. In the present study, we investigated the underlying protective mechanism of Dodam on rotenone-induced cytotoxicity in rat neuroblastoma Neuro-2A cells. Treatment with Neuro-2A cells with rotenone caused the loss of cell viability, and condensation and fragmentation of nuclei, which was associated with the elevation of ROS level, and lipid peroxidation, the increase in Bax/Bcl-2 ratio. Rotenone induced mitochondrial dysfunction characterized by mitochondrial membrane potential loss and cytochrome-c release. These phenotypes induced by rotenone were reversed by pretreatment with Dodam. Our results suggested that major features of rotenone-induced neurotoxicity are partially mediated by mitochondrial dysfunction and oxidative stress, and that Dodam markedly protects Neuro-2A cells from oxidative injury. These data indicated that Dodam might provide a useful therapeutic strategy in treatment of the neurodegenerative diseases caused by oxidative injuries.

• Molecules and Cells
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• 제42권4호
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• pp.292-300
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• 2019

Immunometabolism, defined as the interaction of metabolic pathways with the immune system, influences the pathogenesis of metabolic diseases. Metformin and carbon monoxide (CO) are two pharmacological agents known to ameliorate metabolic disorders. There are notable similarities and differences in the reported effects of metformin and CO on immunometabolism. Metformin, an anti-diabetes drug, has positive effects on metabolism and can exert anti-inflammatory and anti-cancer effects via adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent mechanisms. CO, an endogenous product of heme oxygenase-1 (HO-1), can exert anti-inflammatory and antioxidant effects at low concentration. CO can confer cytoprotection in metabolic disorders and cancer via selective activation of the protein kinase R-like endoplasmic reticulum (ER) kinase (PERK) pathway. Both metformin and CO can induce mitochondrial stress to produce a mild elevation of mitochondrial ROS (mtROS) by distinct mechanisms. Metformin inhibits complex I of the mitochondrial electron transport chain (ETC), while CO inhibits ETC complex IV. Both metformin and CO can differentially induce several protein factors, including fibroblast growth factor 21 (FGF21) and sestrin2 (SESN2), which maintain metabolic homeostasis; nuclear factor erythroid 2-related factor 2 (Nrf2), a master regulator of the antioxidant response; and REDD1, which exhibits an anticancer effect. However, metformin and CO regulate these effects via different pathways. Metformin stimulates p53- and AMPK-dependent pathways whereas CO can selectively trigger the PERK-dependent signaling pathway. Although further studies are needed to identify the mechanistic differences between metformin and CO, pharmacological application of these agents may represent useful strategies to ameliorate metabolic diseases associated with altered immunometabolism.

• Journal of Microbiology and Biotechnology
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• 제31권2호
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• pp.217-225
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• 2021

This study aimed to investigate the neuroprotective effects of 1-methoxylespeflorin G11 (MLG), a pterocarpan, against glutamate-induced neurotoxicity in neuronal HT22 hippocampal cells. The protective effects of MLG were evaluated using MTT assay and microscopic analysis. The extent of apoptosis was studied using flow cytometric analysis performed on the damaged cells probed with annexin V/propidium iodide. Moreover, mitochondrial reactive oxygen species (ROS) were assessed using flow cytometry through MitoSOXTM Red staining. To determine mitochondrial membrane potential, staining with tetramethylrhodamine and JC-1 was performed followed by flow cytometry. The results demonstrated that MLG attenuates glutamate-induced apoptosis in HT22 cells by inhibiting intracellular ROS generation and mitochondrial dysfunction. Additionally, MLG prevented glutamate-induced apoptotic pathway in HT22 cells through upregulation of Bcl-2 and downregulation of cleaved PARP-1, AIF, and phosphorylated MAPK cascades. In addition, MLG treatment induced HO-1 expression in HT22 cells. These results suggested that MLG exhibits neuroprotective effects against glutamate-induced neurotoxicity in neuronal HT22 cells by inhibiting oxidative stress and apoptosis.

• 대한화장품학회지
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• 제43권4호
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• pp.281-287
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• 2017

피부에 가해지는 스트레스는 헤어조절 및 사이클에 직 간접적으로 중요한 영향을 미친다고 알려져 있다. 특히, 모근세포는 스트레스에 의한 부신피질관련호르몬과 세포손상 및 사멸과 밀접한 관련이 있다고 보고되고 있지만, 현재까지 실험적으로 입증된 사실은 매우 제한되어 있다. 보고에 의하면, 부신피질자극호르몬방출인자가 증가되면 모근세포의 마이토콘드리아 활성을 저해하여 초기단계의 세포사멸을 가져올 수 있다고 임상학적으로 보고된바가 있다. 특히 아토피 피부염으로 인한 스트레스는 부신피질자극호르몬방출인자와 부신피질관련 호르몬의 양을 증가시키며, 이는 모발의 outer epithelial sheath에 영향을 준다고 알려져 있으며, 이러한 스트레스의 변화는 마이토콘드리아 손상을 초래하여 초기단계세포손상을 준다고 한다. 따라서 본 연구는 아토피피부염스트레스가 피부의 모근세포에 주는 영향에 대하여 연구를 하였는데, 이에 대한 연구는 현재까지 전무한 실정이다. 우리는 NC/Nga 마우스에 2,4-dinitrochlorobenzene (DNCB)로 아토피피부염을 유발 후, 피부 스트레스 생성에 의한 초기단계 세포손상을 스트레스관련 인자, 부신피질자극호르몬방출인자 및 그 관련 인자, annexin V 및 마이토콘드리아 반응을 이용하여 연구하였다. 그 결과, 아토피피부염에 의한 스트레스는 체내의 부신피질 자극호르몬방출인자 및 관련인자의 활성을 증가시킬 뿐 아니라, 모근세포에 영향을 주어 초기단계세포사멸을 초래하는 것으로 나타났다. 이는 아토피피부염관련 헤어손상을 일으킨다는 중요한 연구결과를 보고하는 바이며, 부신피질자극호르몬 조절관련 의약품 및 화장품 등과 같은 보조적 요법이 필요함을 제안한다.

• 한방비만학회지
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• 제19권1호
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• pp.1-11
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• 2019

Objectives: The purpose of the present study was to evaluate the preventive effects of ethanol extract of Polygalae radix (EEPR) against oxidative stress (hydrogen peroxide, $H_2O_2$)-induced DNA damage and apoptosis in Chang liver cells. Methods: Chang liver cells were pretreated with various concentrations of EEPR and then challenged with 0.5 mM $H_2O_2$. The cell viability and apoptosis were assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and flow cytometry analysis, respectively. The levels of reactive oxygen species (ROS), mitochondrial membrane potentials (MMPs) and adenosine tri-phosphate (ATP) contents were measured. Expression levels of Bcl-2 and Bax were also determined using Western blot analysis. Results: The results showed that the decreased survival rate induced by $H_2O_2$ could be attributed to the induction of DNA damage and apoptosis accompanied by the increased production of ROS, which was remarkably protected by EEPR. In addition, the loss of $H_2O_2$-induced MMPs and ATP contents was significantly attenuated in the presence of EEPR. The inhibitory effect of EEPR on $H_2O_2$-induced apoptosis was associated with up-regulation of Bcl-2 and down-regulation of Bax, thus reducing the Bax/Bcl-2 ratio. Conclusions: Our data prove that EEPR protects Chang liver cells against $H_2O_2$-induced DNA damage and apoptosis by scavenging ROS and thus suppressing the mitochondrial-dependent apoptosis pathway.