• BMB Reports
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• 제38권6호
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• pp.709-716
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• 2005

Apoptosis and necrosis are distinguished by modality primarily. Here we show an apoptosis occurred instantly, induced by $300\;{\mu}M$ W-7 ((N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide hydrochloride), inhibitor of calmodulin), which demonstrated necrotic modality. As early as 30 min after W-7 addition, apoptotic (sub-diploid) peak could be detected by fluorescence-activated cell sorter (FACS), “DNA ladders” began to emerge also at this time point, activity of caspase-3 elevated obviously within this period. Absence of mitochondrial membrane potential (MMP) reduction and cytochrome c, AIF (apoptosis inducing factor) release, verified that this rapid apoptosis did not proceed through mitochondria pathway. Activation of caspase-12 and changes of other endoplasmic reticulum (ER) located proteins ascertained that ER pathway mediated this necrosis-like apoptosis. Our findings suggest that it is not credible to judge apoptosis by modality. Elucidation of ER pathway is helpful to comprehend the pathology of diseases associated with ER stress, and may offer a new approach to the therapy of cancer and neurodegenerative diseases.

• BMB Reports
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• 제49권3호
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• pp.159-166
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• 2016

Several members of tumor necrosis factor receptor (TNFR) superfamily that these members activate caspase-8 from death-inducing signaling complex (DISC) in TNF ligand-receptor signal transduction have been identified. In the extrinsic pathway, apoptotic signal transduction is induced in death domain (DD) superfamily; it consists of a hexahelical bundle that contains 80 amino acids. The DD superfamily includes about 100 members that belong to four subfamilies: death domain (DD), caspase recruitment domain (CARD), pyrin domain (PYD), and death effector domain (DED). This superfamily contains key building blocks: with these blocks, multimeric complexes are formed through homotypic interactions. Furthermore, each DD-binding event occurs exclusively. The DD superfamily regulates the balance between death and survival of cells. In this study, the structures, functions, and unique features of DD superfamily members are compared with their complexes. By elucidating structural insights of DD superfamily members, we investigate the interaction mechanisms of DD domains; these domains are involved in TNF ligand-receptor signaling. These DD superfamily members play a pivotal role in the development of more specific treatments of cancer.

• The Korean Journal of Physiology and Pharmacology
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• 제16권4호
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• pp.225-230
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• 2012

We investigated the effects of ${\beta}$-glucan purified from Paenibacillus polymyxa JB115 on the viability and proliferation of splenocytes. Splenocytes play a critical role in host immunity. MTT assays and trypan blue exclusion tests revealed that ${\beta}$-glucan significantly promoted the viability and proliferation of splenocytes over a range of concentrations. However, there was no specific subset change. ${\beta}$-glucan protected splenocytes from cytokine withdrawal-induced spontaneous cell death. For further mechanistic studies, ELISA assay revealed that ${\beta}$-glucan enhanced the expression of anti-apoptotic molecules and interleukin 7 (IL-7), a cytokine critical for lymphocyte survival. We also investigated the IL-2 dependency of ${\beta}$-glucan-treated splenocytes to determine if treated cells could still undergo clonal expansion. In flow cytometric analysis, ${\beta}$-glucan induced increased levels of the activation marker CD25 on the surface of splenocytes and ${\beta}$-glucan-treated splenocytes showed higher proliferation rates in response to IL-2 treatment. This study demonstrates that ${\beta}$-glucan can enhance the survival of splenocytes and provides valuable information to broaden the use of ${\beta}$-glucan in research fields.

• Journal of Korean Neurosurgical Society
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• 제41권1호
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• pp.30-38
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• 2007

Objective : To elucidate the role of aquaporin-4[AQP4] in cerebral edema formation, we studied the expression and subcellular localization of AQP4 in astrocytes after focal cerebral ischemia. Methods : Cerebral ischemia were induced by permanent middle cerebral artery[MCA] occlusion in rats and estimated by the discoloration after triphenyltetrazolium chloride[TTC] immersion. Change of AQP4 expression were evaluated using western blot. Localization of AQP4 was assessed by confocal microscopy and its interaction with ${\alpha}-syntrophin$ was analyzed by immunoprecipitation. Results : After right MCA occlusion, the size of infarct and number of apoptotic cells increased with time. The ratio of GluR1/GluR2 expression also increased during ischemia. The polarized localization of AQP4 in the endfeet of astrocytes contacting with ventricles, vessels and pia mater was changed into the diffuse distribution in cytoplasm. The interactions of AQP4 and Kir with ${\alpha}-syntrophin$, an adaptor of dystrophin complex, were disrupted by cerebral ischemia. Conclusion : The deranged spatial buffering function of astrocytes due to mislocalized AQP4/Kir4.1 channel as well as increased assembly of $Ca^{2+}$ permeable AMPA receptors might contribute to the development of edema formation and the excitotoxic neuronal cell death during ischemia.

• Asian Pacific Journal of Cancer Prevention
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• 제15권23호
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• pp.10137-10142
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• 2015

Apoptosis is a general phenomenon of all multicellular organisms and caspases form a group of important proteins central to suicide of cells. Pathologies like cancer, Myocardial infarction, Stroke, Sepsis, Alzheimer's, Psoriasis, Parkinson and Huntington diseases are often associated with change in caspase 3 mediated apoptosis and therefore, caspases may serve as potential inhibitory targets for drug development. In the present study, two series of synthetic acetylated tetrapeptides containing aldehyde and fluromethyl keto groups respectively at the C terminus were proposed. All these compounds were evaluated for binding affinity against caspase 3 structure. In series 1 compound Ac-DEHD-CHO demonstrated appreciable and high binding affinity (Rerank Score: -138.899) against caspase 3. While in series 2 it was Ac-WEVD-FMK which showed higher binding affinity (Rerank Score: -139.317). Further these two compounds met ADMET properties and demonstrated to be non-toxic.

• Asian Pacific Journal of Cancer Prevention
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• 제15권12호
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• pp.4753-4758
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• 2014

In recent times, a number of studies have provided evidence that biotoxins present great potential as antitumor agents, such as snake venom, bee venom, some bacteria toxins and plant toxins, and thus could be used as chemotherapeutic agents against tumors. The biodiversity of venoms and toxins make them a unique source from which novel anticancer agent may be developed. Biotoxins, also known as natural toxins, include toxic substances produced by plants, animals and microorganisms. Here, we systematically list representative biological toxins that have antitumor properties, involving animal toxins, plant toxins, mycotoxins as well as bacterial toxins. In this review, we summarize the current knowledge involving biotoxins and the active compounds that have anti-cancer activity to induce cytotoxic, antitumor, immunomodulatory, and apoptotic effects in different tumor cells in vivo or in vitro. We also show insights into the molecular and functional evolution of biotoxins.

• Journal of Korean Neurosurgical Society
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• 제38권4호
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• pp.293-298
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• 2005

Objective : The authors investigate the spatial characteristics of apoptotic genes expressed around the focal cerebral infarction, and attempted to explain the penumbra with them. Methods : A delayed focal cerebral infarction was created in twelve adult Sprague-Dawley rats. We performed the immunohistochemical staining for the apoptosis, bcl-2 and p53 proteins and measured the local cerebral blood flow [CBF] at the infarction core area and peri-infarct area pre- and intra-operatively. The peri-infarct area was divided into six sectors by distance from the infarction border. Results : The size [$mm^2$] of apoptosis, bcl-2, and p53 areas were $3.1{\pm}1.2$, $4.7{\pm}2.1$, and $6.8{\pm}2.4$, respectively. Apoptosis, bcl-2 or p53 positive cells were concentrated at the peri-infarct area adjacent to the infarction core. Their numbers reduced peripherally, which was inversely proportional to the local CBF. The p53 area seems to overlap with and larger than the ischemic penumbra. Conclusion : The p53 positive area provides a substitutive method defining the penumbra under the molecular base of knowledge.

• Asian Pacific Journal of Cancer Prevention
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• 제17권8호
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• pp.3797-3803
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• 2016

Cervical cancer is the second most common malignancy in women worldwide and thus one of the leading causes of mortality in women. Lovastatin, a non polar, anticholesterol drug has previously been reported to exert antitumour activity in vitro. In the present study, lovastatin from Aspergillus terreus (KM017963) was purified by adsoprtion chromatography and evaluated for its anticancer and anti-oxidant properties with a human cervical cancer cell line (HeLa). Growth inhibitory and proapoptotic effects of purified lovastatin on HeLa cells were investigated by determining its influence on cell numbers, mitochondrial membrane potential (MMP), DNA fragmentation and antioxidant properties in terms of hydroxy radical scavenging effects as well as levels of total reduced glutathione. Cell cycle analysis by flow cytometry (propidium iodide staining) confirmed induction of apoptotic cell death and revealed cell cycle arrest in the G0/G1 phase. Results of the study give leads for the anticancer effects of lovastatin and its potential usefulness in the chemotherapy of cervical cancer.

• Journal of Chest Surgery
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• 제32권2호
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• pp.151-157
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• 1999

배경: 많은 실험적인 연구에서 종양 조직 내의 아포프토시스와 미세 혈관의 생성은 서로 반비례한다고 보고된다. 비소세포 폐암 조직내에서 두 수치의 관계를 조사하여 보았다. 대상 및 방법:조직내의 아포프토시스의 정도는 deoxynucleotidyl trasferase방법으로(Apop Tag In Situ Apoptosis Detection Kit, ONCOR) 측정하였고, 종양내 미세 혈관 밀도는 항 CD 31 항체를 이용하였다. 결과:아포프토시스 지수와 종양내 미세 혈관 밀도 사이에는 통계적으로 유의하게 역 상관관계가 있었다(p = 0.047). 결론: 비소세포 폐암종에서 아포프토시스와 미세 혈관 생성의 정도는 서로 연관이 있다고에 할 수있다. 그리고 종양내의 신생 혈관의 생성이 종양내 아포프토시스의 억제에 기여한다고 유추 할 수 있다.

• 한국생물공학회:학술대회논문집
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• 한국생물공학회 2000년도 추계학술발표대회 및 bio-venture fair
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• pp.208-211
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• 2000

본 연구를 통해 환경 유해성을 평가하기 위한 동물세포를 개발했고 이를 이용한 모니터링 방법 연구와 다양한 독성 물질에 대한 반응성을 확인했다. 개발된 독성 모니터링 동물세포(KFC-A10)는 각 독성 물질에 따라 빛의 발현 양이 증가하는 성향을 가지므로 이번 실험에서 사용된 MMC, BPA, ${\gamma}-ray$에 농도 의존적으로 빛의 양이 증가함을 관찰할 수 있었다. 특히 BPA의 경우는 환경호르몬으로 알려진 바 그 estrogenic 효과를 관찰할 수 있었다.