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Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis
Wei-Chung Hsieh,Pei-Chen Hsu,Ya-Fan Liao,Shu-Ting Young,Zeng-Wei Wang,Chih-Li Lin,Gregory J. Tsay,Huei Lee,Hui-Chih Hung,Guang-Yaw Liu 한국분자세포생물학회 2010 Molecules and cells Vol.30 No.4
Ornithine decarboxylase (ODC), the key enzyme of poly-amine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC pre-vents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/en-doplasmic reticulum (ER) Ca2+ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpres-sion of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homolo-gous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC pre-served the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-medi-ated apoptotic pathway, induced by TG. Finally, overex-pression of ODC maintains the protein and mRNA expres-sion of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.
생강나무(Lindera obtusiloba Blume) 잎 70% 에탄올 추출물의 단회와 14일 반복투여 독성시험의 안전성 평가
홍충의(Chung-Oui Hong),서문영(Young Seomun),구윤창(Yun-Chang Koo),남미현(Mi-Hyun Nam),이현아(Hyun Ah Lee),김지훈(Ji-Hoon Kim),왕증(Wang-Zeng),양성용(Sung Yong Yang),이성희(Sung-Hee Lee),노수환(Su Hwan No),이광원(Kwang-Won Lee) 한국식품영양과학회 2009 한국식품영양과학회지 Vol.38 No.10
생강나무는 한국, 일본, 중국 등지에서 자생하며 열, 복통, 타박상, 출혈 등에 민간요법으로 사용되어온 식물이다. 이 논문의 목적은 오래전부터 민간요법으로 사용되어온 생강나무 잎의 안전성을 평가하고자 생강나무 잎 70% 에탄올 추출물을 암수 각 군당 5마리씩 5000(단회투여 독성시험), 0, 500, 1000, 2000(14일 반복투여 독성시험) ㎎/㎏의 용량으로 단회경구투여와 14일 반복경구투여를 실시하여 15일간의 사망률, 일반증상, 체중변화, 조직병리, 혈액학적 및 혈액 생화학적 검사를 실시하였다. 시험기간 중 사망동물은 암수 모든 시험군에서 관찰되지 않았으며, 일반증상, 체중변화, 조직병리, 혈액학적 및 혈액생화학적 검사에서 투여와 관련된 변화는 관찰되지 않았다. 이상의 결과로 보아 생강나무의 단회투여 독성은 5000 ㎎/㎏ 용량을 상회하며, 14일 반복투여의 최고용량인 2000 ㎎/㎏ 용량에서도 아무런 독성이 나타나지 않는 것으로 보아 최대무독성량은 이 농도를 상회하는 것으로 판단된다. 이로써 생강나무는 안전한 소재로서 식재료 또는 건강기능식품의 원료로서도 사용이 가능하다고 볼 수 있다. Lindera obtusiloba Blume (LO), which is widely distributed in Korea, Japan and China, has traditionally been used as a popular folk medicine for the treatment of fever, abdominal pain, bruise and extravation. The purpose of this study was to examine the toxicities of the single and 14-day repeated doses in Sprague-Dawley rats orally administrated with LO at doses of 0, 500, 1000, 2000 (14-day repeated toxicity test) and 5000 (single toxicity test) mg (dry weight)/㎏ of body weight/day. The results showed that there was no difference in body weight change, food intake, water consumption, or organ weight among different dose groups. Also we observed no death and abnormal clinical signs during the experimental period. Between the groups orally administered LO and the control group, there was no statistical significance in hematological test or serum biochemical values. There were no evidences of histopathological alteration as well as abnormal gross finding mediated by single and 14 days treatments with LO. These results suggest that no observed adverse effect level (NOAEL) of the oral application of LO was considered to be more than 2000 mg/kg in rats under the conditions employed in this study.
Overexpression of Ornithine Decarboxylase Suppresses Thapsigargin-Induced Apoptosis
Hsieh, Wei-Chung,Hsu, Pei-Chen,Liao, Ya-Fan,Young, Shu-Ting,Wang, Zeng-Wei,Lin, Chih-Li,Tsay, Gregory J.,Lee, Huei,Hung, Hui-Chih,Liu, Guang-Yaw Korean Society for Molecular and Cellular Biology 2010 Molecules and cells Vol.30 No.4
Ornithine decarboxylase (ODC), the key enzyme of polyamine biosynthesis, has paradoxical roles in apoptosis. Our published papers show overexpression of ODC prevents the apoptosis induced by many cytotoxic drugs. Thapsigargin (TG) is an inhibitor of the sarcoplasmic/endoplasmic reticulum (ER) $Ca^{2+}$ ATPase (SERCA) pumps and causes ER stress-induced apoptosis. We used ODC overexpressing cell lines to examine whether overexpression of ODC inhibits TG-induced apoptosis. Our results indicated overexpression of ODC attenuated TG-induced apoptosis. Overexpression of ODC blocked procaspse-4 cleavage and phosphorylation of protein kinase-like ER-resident kinase (PERK), triggered by TG. It also attenuated the increase in CAAT/enhancer binding protein homologous protein (CHOP). Cells with overexpressed ODC had greater Bcl-2 expression. Overexpression of ODC preserved the expression of Bcl-2, inhibited the increase in Bak and stabilized mitochondrial membrane potential without the influences of TG. Cytochrome c release and downstream caspase activation were blocked. That is, overexpression of ODC inhibits the mitochondria-mediated apoptotic pathway, induced by TG. Finally, overexpression of ODC maintains the protein and mRNA expression of SERCA. In conclusion, overexpression of ODC suppresses TG-induced apoptosis by blocking caspase-4 activation and PERK phosphorylation, attenuating CHOP expression and inhibiting the mitochondria-mediated apoptotic pathway.
Nai-Yun Chang,Zeng-Weng Chen,Ter-Hsin Chen,Jiunn-Wang Liao,Cheng-Chung Lin,Maw-Sheng Chien,Wei-Cheng Lee,Jiunn-Horng Lin,Shih-Ling Hsuan 대한수의학회 2014 Journal of Veterinary Science Vol.15 No.1
Exotoxins produced by Actinobacillus (A.) pleuropneumoniae(Apx) play major roles in the pathogenesis of pleuropneumoniain swine. This study investigated the role of ApxI in hemolysisand cellular damage using a novel apxIA mutant, ApxIA336,which was developed from the parental strain A. pleuropneumoniae serotype 10 that produces only ApxI in vitro. The genotype of ApxIA336 was confirmed by PCR, Southernblotting, and gene sequencing. Exotoxin preparation derivedfrom ApxIA336 was analyzed for its bioactivity towardsporcine erythrocytes and alveolar macrophages. Analysisresults indicated that ApxIA336 contained a kanamycinresistantcassette inserted immediately after 1005 bp of theapxIA gene. Phenotype analysis of ApxIA336 revealed nodifference in the growth rate as compared to the parentalstrain. Meanwhile, ApxI production was abolished in thebacterial culture supernatant, i.e. exotoxin preparation. Theinability of ApxIA336 to produce ApxI corresponded to the lossof hemolytic and cytotoxic bioactivity in exotoxin preparation,as demonstrated by hemolysis, lactate dehydrogenase release,mitochondrial activity, and apoptosis assays. Additionally, thevirulence of ApxIA336 appeared to be attenuated by 15-fold inBALB/c mice. Collectively, ApxI, but not other components inthe exotoxin preparation of A. pleuropneumoniae serotype 10,was responsible for the hemolytic and cytotoxic effects onporcine erythrocytes and alveolar macrophages.
Hybrid Navigation of a Four-Wheeled Tour-Guide Robot
Yuan-Pao Hsu,Ching-Chih Tsai,Zeng-Chung Wang,Yi-Jiang Feng,Hung-Hsing Lin 제어로봇시스템학회 2009 제어로봇시스템학회 국제학술대회 논문집 Vol.2009 No.8
This paper develops methodologies and techniques for motion control and autonomous navigation of a tour-guide robot with a four-wheeled omni-directional mobile platform. A nonlinear unified kinematical control method is presented for point stabilization and trajectory tracking of a mobile robot which equipped with four independent driving omni-directional wheels equally spaced at 90 degrees between adjacent wheels. A hybrid navigation method is proposed to achieve safely autonomous navigation of the tour-guide robot; this approach includes two behaviors: one is the point-to-point trajectory tracking, and the other is the obstacle avoidance function using the traversability distance histogram (TDH) method to avoid barriers in museums. The effectiveness and merit of the proposed techniques are exemplified by conducting several experiments on an experimental four-wheeled omni-directional tour-guide robot.