• Biomedical Science Letters
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• v.26 no.4
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• pp.336-343
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• 2020

The present study was carried out to investigate the possibility that bispidinone derivative makes anticancer drug availability to human cervical carcinoma cell. The B8 has the lowest IC50 value among B8, B9 and B10 which are bispidinone analogue with bromide. According to cytotoxic test through WST-8 assay, B8 shows the most magnificent cytotoxicity effectiveness with 76 μM of IC50 value. In human cervical carcinoma cell treated with B8, it noticeably controlled cellular multiplication by increase of concentration and time. Furthermore, morphological changes like cellular shrink, disruption and nuclear condensation, feature of apoptosis, are observed. Annexin V-FITC/PI double staining assay test proved that B8 can cause apoptosis. Moreover, after treatment with 76 μM of B8, flow cytometry analysis shows that increase of active oxygen species are induced and membrane potential in mitochondria is decreased. Manifestation of Bcl-2 family and caspase cascades protein provides evidence that B8 induces apoptosis through mitochondria and caspase-related pathway. Taken together, we suggested that B8 reduced membrane potential in mitochondria and induce apoptosis through the pathway depended on mitochondria and caspase.

• BMB Reports
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• v.38 no.5
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• pp.619-623
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• 2005

The efficacy of chemotherapeutic agents on tumor cells has been shown to be modulated by tumor suppressor gene p53 and its target genes such as Bcl-2 family members (Bax, Noxa, and PUMA). However, various chemotherapeutic agents can induce cell death in tumor cells that do not express the functional p53, suggesting that some chemotherapeutic agents may induce cell death in a p53-independent pathway. Here we showed that etoposide can induce the similar degree of cell death in p53-deficient HCT 116 cells, whereas 5'-FU-mediated cell death is strongly dependent on the existence of functional p53 in HCT 116 cells. Further, we provide the evidence that etoposide can induce the cytochrome c release from isolated mitochondria, and etoposide-induced cytochrome c release is not accompanied with the large amplitude swelling of mitochondria. These data suggest that etoposide can directly induce the mitochondrial dysfunction irrespective of p53 status, and it may, at least in part, account for the p53-independent pathway in cell death induced by chemotherapeutic agents.

• Molecules and Cells
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• v.37 no.2
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• pp.89-94
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• 2014

Fission and fusion of mitochondrial tubules are the main processes determining mitochondrial shape and size in cells. As more evidence is found for the involvement of mitochondrial morphology in human pathology, it is important to elucidate the mechanisms of mitochondrial fission and fusion. Mitochondrial morphology is highly sensitive to changing environmental conditions, indicating the involvement of cellular signaling pathways. In addition, the well-established structural connection between the endoplasmic reticulum (ER) and mitochondria has recently been found to play a role in mitochondrial fission. This minireview describes the latest advancements in understanding the regulatory mechanisms controlling mitochondrial morphology, as well as the ER-mediated structural maintenance of mitochondria, with a specific emphasis on mitochondrial fission.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.41-41
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• 1992

새로이 합성된 1,4-Naphthoquinone(1,4-NQ) 화합물의 세포독성의 확인과 그 작용기전을 규명코져 본 실험을 수행하였다. 분리된 흰쥐 간세포를 1,4-NQ유도체들과 반응 시켰을때 이들 중 YC 001과 YC 008은 독성을 나타냈으나 YC 012는 독성율 나타내지 아니하였다. 세포독성은 세포치사, lactate dehydrogenase 유출 및 산소소비의 억제등으로 확인하였다. 세포 독성의 기전은 mitochondria에서의 전자흐름 차단작용과 microsome에서 redox-cycling 기전에 의한 산소리디칼 생성의 두가지에 대하여 검토하였다. 분리된 mitochondria를 YC 001과 YC 008은 반응 시켰을때 mitochondria의 호흡은 완전히 억제되었다. 그러나 YC 012는 전혀 작용을 나타내지 아니하였다. 이는 간세포에 대한 독성작용과 일치하는 결과이며 따라서 mitochondria에 대한 억제 작용은 이들의 세포독성에 주요한 요인이라고 추측되었다.

• Applied Microscopy
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• v.19 no.2
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• pp.59-73
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• 1989

To investigate the effect of cadmium and cadmium binding protein on the electron transport system and conformational changes of rat kidney mitochondria, various cadmium concentration were treated in vitro and respiration rate, NADH-CoQ reductase activity were measured. Ultrastructural changes at state IV respiration were also observed. CdBP was isolated from the rat liver by Sephadex G-75 column fractionation and treated in vitro with cadmium. Also mitochondrial state IV respiration rate was measured. When cadmium was treated in vitro, state IV respiration and enzyme activity were decreased and ultrastructural transformation of mitochondria from a condensed to an orthodox conformation was inhibited under state IV respiration. In case cadmium and CdBP were treated together, oxygen consumption was more increased than cadmium only. Conformational changes of mitochondria from a condensed to orthodox conformation were also observed. This indicates that CdBP have a protective effect against cadmium toxicity.

• Korean Journal of Veterinary Research
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• v.36 no.3
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• pp.565-570
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• 1996

Cardiac, hepatic and renal mitochondria in rats fed lead containing diets were isolated and their activities were studied in terms of NADH oxidation. In normal rats, cardiac and renal mitochondria had similar activities and showed activity values of higher than those in hepatic mitochondria. Cardiac mitochondiral activities in rats fed lead containing diets were increased after 4 weeks of feeding but decreased to activity values close to normal. Renal mitochondrial activities showed a trend of inhibition in all groups fed lead containing diets but were no differenes by feeding periods of 4 and 8 weeks. Feeding of lead containing diets could not be attributed to any changes in the hepatic mitochondrial antivities at experimental doses during 4~8 weeks.

• The Korean Journal of Zoology
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• v.30 no.3
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• pp.239-247
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• 1987

생쥐 신장의 근위세뇨관과 원위세뇨관 세포의 미세구조에 미치는 염화 메틸수은의 독성에 대한 홍삼유출물의 첨독성적 영향을 전자현징경적으로 연구하였다. 염화 메틸수은 처리군의 근위세뇨관 세포에서는 대조군에서 보다 철세 융모가 다소 축소되고 불규칙한 배열을 하였다. Brush border의 인접 부위에서는 작은 경계들이 나타나고 세포질 중앙 부위에서는 치밀체를 함유한 큰 육포들이 관색되었다. Mitochondria는 상당히 팽대되고 기양막은 부분적으로 비후되었으며 다수의 ITsosome이 나타났다. 염화 메틸수은 처리군의 원위세뇨관 세롱에서는 불규칙한 세포 표면, 양사된 세포, 그리고 다수의 ribosome과 소수의 지방사이 나타났으며 mitochondria 는 팽대되고 기고막은 부분적으로 비후되었다. 염화 메틸수은-홍삼추출물 병행 처리군의 근위세뇨관 세포에서는 염화 메틸수은 처리군에서 보다 mitochondria의 팽대 정도가 감소되었으며 육포의 크기와 수도 상당히 감소되었다. 염화 메틸수은-홍모적출물 병행 처리군의 원위세뇨관 세롱에서는 세포 표면이 어느정도 규칙적이고 mitochondria의 정해와 기저막의 비후 정도가 감소되어 정상 세포와 거의 유사하였다.

• BMB Reports
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• v.48 no.10
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• pp.541-548
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• 2015

Cardiomyopathy is an inherited or acquired disease of the myocardium, which can result in severe ventricular dysfunction. Mitochondrial dysfunction is involved in the pathological process of cardiomyopathy. Many dysfunctions in cardiac mitochondria are consequences of mutations in nuclear or mitochondrial DNA followed by alterations in transcriptional regulation, mitochondrial protein function, and mitochondrial dynamics and energetics, presenting with associated multisystem mitochondrial disorders. To ensure correct diagnosis and optimal management of mitochondrial dysfunction in cardiomyopathy caused by multiple pathogenesis, multidisciplinary approaches are required, and to integrate between clinical and basic sciences, ideal translational models are needed. In this review, we will focus on experimental models to provide insights into basic mitochondrial physiology and detailed underlying mechanisms of cardiomyopathy and current mitochondria-targeted therapies for cardiomyopathy.

• BMB Reports
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• v.53 no.1
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• pp.35-46
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• 2020

Despite enduring diverse insults, mitochondria maintain normal functions through mitochondrial quality control. However, the failure of mitochondrial quality control resulting from excess damage and mechanical defects causes mitochondrial dysfunction, leading to various human diseases. Recent studies have reported that mitochondrial defects are found in Alzheimer's disease (AD) and worsen AD symptoms. In AD pathogenesis, mitochondrial dysfunction-driven generation of reactive oxygen species (ROS) and their contribution to neuronal damage has been widely studied. In contrast, studies on mitochondrial dysfunction-associated inflammatory responses have been relatively scarce. Moreover, ROS produced upon failure of mitochondrial quality control may be linked to the inflammatory response and influence the progression of AD. Thus, this review will focus on inflammatory pathways that are associated with and initiated through defective mitochondria and will summarize recent progress on the role of mitochondria-mediated inflammation in AD. We will also discuss how reducing mitochondrial dysfunction-mediated inflammation could affect AD.

• BMB Reports
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• v.52 no.12
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• pp.679-688
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• 2019

The decrease of metabolism in the brain has been observed as the important lesions of Alzheimer's disease (AD) from the early stages of diagnosis. The cumulative evidence has reported that the failure of mitochondria, an organelle involved in diverse biological processes as well as energy production, maybe the cause or effect of the pathogenesis of AD. Both amyloid and tau pathologies have an impact upon mitochondria through physical interaction or indirect signaling pathways, resulting in the disruption of mitochondrial function and dynamics which can trigger AD. In addition, mitochondria are involved in different biological processes depending on the specific functions of each cell type in the brain. Thus, it is necessary to understand mitochondrial dysfunction as part of the pathological phenotypes of AD according to each cell type. In this review, we summarize that 1) the effects of AD pathology inducing mitochondrial dysfunction and 2) the contribution of mitochondrial dysfunction in each cell type to AD pathogenesis.