• Title/Summary/Keyword: cytochrome $c_3$

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Inhibition of Apoptosis is Responsible for the Acquired Resistance of K562 Cells to Cisplatin

  • Lee, Soo-Yong;Kim, Dong-Hyun
    • Biomolecules & Therapeutics
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    • v.12 no.2
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    • pp.85-91
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    • 2004
  • In all attempt to elucidate the role of apoptosis in drug resistance, cisplatin-resistant human chronic myelogenous leukemia (CML) K562 cells (K562/CDDP) were established and compared with drug sensitive parent cells (K562) in the induction of apoptosis. K562/CDDP cells were 5-fold more resistant to cisplatin compared to K562 cells. In addition, K562/CDDP cells were significantly more resistant to apoptois as judged by DNA fragmentation and DAPI staining. K562/CDDP cells exhibited decreased proleolytic activity of caspase-3 and this was further demonstrated by decreased cleavage of its substrate poly (ADP-ribose) polymerase (PARR- Western blot analysis showed that K562/CDDP cells had longer sustained levels of BCL-$X_L$ whereas no difference was noted in the level of Bcl-2. the translocation of Bax to mitochondria was significantly delayed in K562/CDDP cells. These results suggest that the reduced translocation of Bax and the sustained expression of BCL-$X_L$ may cause resistance to apoptosis through prevention of mitochondria release of cytochrome c, which subsequently induces reduction of caspase-3 activity and that this response is partly responsible for the acquired resistance to cisplatin ill K562 cells.

Effects of Naringin on the Bioavailability of Etoposide in Rats

  • Choi, Byung-Chul;Choi, Jun-Shik
    • Journal of Pharmaceutical Investigation
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    • v.38 no.5
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    • pp.313-317
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    • 2008
  • This study investigated the effect of naringin, a flavonoid, on the bioavailability of etoposide administered orally to rats. Etoposide (6 mg/kg) was administered orally to rats alone or with naringin (1, 4 or 12 mg/kg). Compared with the control group, the co-administration of etoposide with 4 and 12 mg/kg of naringin significantly (p<0.05) increased the area under the plasma concentration-time curve (AUC) and the peak plasma concentration ($C_{max}$) of the oral etoposide. Consequently, the absolute bioavailability (AB) of etoposide in the presence (4 and 12 mg/kg) of naringin was significantly (p<0.05) increased by $9.4{\sim}10.6%$ compared with the control group (7.4%). The relative bioavailability (RB) of etoposide was increased 1.13- to 1.44-fold compared to the control group. Enhanced bioavailability of etoposide might be due to inhibition of both cytochrome P450 (CYP) 3A4 in the intestine or liver and P-glycoprotein (P-gp) transport efflux of etoposide in the intestinal membrane. This data indicate that careful consideration of the dosage for therapy with etoposide is required in a case of clinical application of the co-administration of etoposide and naringin.

Effects of retinoic acid isomers on apoptosis and enzymatic antioxidant system in human breast cancer cells

  • Hong, Tae-Kyong;Lee-Kim, Yang-Cha
    • Nutrition Research and Practice
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    • v.3 no.2
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    • pp.77-83
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    • 2009
  • Retinoic acids (RAs) modulate growth, differentiation, and apoptosis in normal, pre-malignant & malignant cells. In the present study, the effects of RA isomers (all-trans RA, 13-cis RA, and 9-cis RA) on the cell signal transduction of human breast cancer cells have been studied. The relationship between RAs and an enzymatic antioxidant system was also determined. Estrogen-receptor (ER) positive MCF-7 and ER-negative MDA-MB-231 human breast cancer cells were treated with different doses of each RA isomers, all-trans RA, 13-cis RA, or 9-cis RA. Treatment of RA isomers inhibited cell viability and induced apoptosis of MCF-7 cells as a result of increased caspase activity in cytoplasm and cytochrome C released from mitochondria. All-trans RA was the most effective RA isomer in both cell growth inhibition and induction of apoptosis in MCF-7 cells. However, no significant effect of RA isomers was observed on the cell growth or apoptosis in ER-negative MDA-MB-231 cells. In addition, activities of antioxidant enzymes such as catalase and glutathione peroxidase were decreased effectively after treatment of RA in MCF-7 cells, whereas SOD activity was rarely affected. Thus, the present data suggest that all-trans RA is the most potential inducer of apoptosis and modulator of antioxidant enzymes among RA isomers in MCF-7 human breast cancer cells.

VvpM Induces Human Cell Death via Multifarious Modes Including Necroptosis and Autophagy

  • Lee, Mi-Ae;Kim, Jeong-A;Shin, Mee-Young;Lee, Jeong K.;Park, Soon-Jung;Lee, Kyu-Ho
    • Journal of Microbiology and Biotechnology
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    • v.25 no.2
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    • pp.302-306
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    • 2015
  • VvpM, one of the extracellular metalloproteases produced by Vibrio vulnificus, induces apoptotic cell death via a pathway consisting of ERK activation, cytochrome c release, and activation of caspases-9 and -3. VvpM-treated cells also showed necrotic cell death as stained by propidium iodide (PI). The percentage of PI-stained cells was decreased by pretreatment with Necrostatin-1, indicating that VvpM-mediated cell death occurs through necroptosis. The appearance of autophagic vesicles and lipidated form of light-chain-3B in rVvpM-treated cells suggests an involvement of autophagy in this process. Therefore, the multifarious action of VvpM might be one of the factors responsible for V. vulnificus pathogenesis.

A Conclusive Review on Amyloid Beta Peptide Induced Cerebrovascular Degeneration and the Mechanism in Mitochondria

  • Merlin, Jayalal L.P.
    • Journal of Integrative Natural Science
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    • v.6 no.3
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    • pp.125-137
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    • 2013
  • Promising evidence suggests that amyloid beta peptide ($A{\beta}$), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in $A{\beta}$-induced apoptosis of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling cascade upstream of mitochondria entails $A{\beta}$ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in $A{\beta}$-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by $A{\beta}$ to induce death of non-neuronal cells are complex. Understanding these apoptosis signalling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular $A{\beta}$ deposition.

Molecular Identification of Diphyllobothrium nihonkaiense from 3 Human Cases in Heilongjiang Province with a Brief Literature Review in China

  • Zhang, Weizhe;Che, Fei;Tian, Song;Shu, Jing;Zhang, Xiaoli
    • Parasites, Hosts and Diseases
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    • v.53 no.6
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    • pp.683-688
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    • 2015
  • Human diphyllobothriasis is a widespread fish-borne zoonosis caused by the infection with broad tapeworms belonging to the genus Diphyllobothrium. In mainland China, so far 20 human cases of Diphyllobothrium infections have been reported, and the etiologic species were identified as D. latum and D. nihonkaiense based on morphological characteristics or molecular analysis. In the present study, proglottids of diphyllobothriid tapeworms from 3 human cases that occurred in Heilongjiang Province, China were identified as D. nihonkaiense by sequencing mitochondrial cytochrome c oxidase subunit I (cox1) and NADH dehydrogenase subunit 5 (nad5) genes. Two different cox1 gene sequences were obtained. One sequence showed 100% homology with those from humans in Japan. The remaining cox1 gene sequence and 2 different nad5 gene sequences obtained were not described previously, and might reflect endemic genetic characterizations. D. nihonkaiense might also be a major causative species of human diphyllobothriasis in China. Meanwhile, the finding of the first pediatric case of D. nihonkaiense infection in China suggests that infants infected with D. nihonkaiense should not be ignored.

Poly(ADP-ribosyl)ation of p53 Contributes to TPEN-Induced Neuronal Apoptosis

  • Kim, Hyun-Lim;Ra, Hana;Kim, Ki-Ryeong;Lee, Jeong-Min;Im, Hana;Kim, Yang-Hee
    • Molecules and Cells
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    • v.38 no.4
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    • pp.312-317
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    • 2015
  • Depletion of intracellular zinc by N,N,N,N-tetrakis(2-pyridylmethyl) ethylenediamine (TPEN) induces p53-mediated protein synthesis-dependent apoptosis of mouse cortical neurons. Here, we examined the requirement for poly(ADP-ribose) polymerase (PARP)-1 as an upstream regulator of p53 in zinc depletion-induced neuronal apoptosis. First, we found that chemical inhibition or genetic deletion of PARP-1 markedly attenuated TPEN-induced apoptosis of cultured mouse cortical neurons. Poly(ADP-ribosyl)ation of p53 occurred starting 1 h after TPEN treatment. Suggesting the critical role of PARP-1, the TPEN-induced increase of stability and activity of p53 as well as poly(ADP-ribosyl)ation of p53 was almost completely blocked by PARP inhibition. Consistent with this, the induction of downstream pro-apoptotic proteins PUMA and NOXA was noticeably reduced by chemical inhibitors or genetic deletion of PARP-1. TPEN-induced cytochrome C release into the cytosol and caspase-3 activation were also blocked by inhibition of PARP-1. Taken together, these findings indicate that PARP-1 is essential for TPEN-induced neuronal apoptosis.

Dual positional substrate specificity of rice allene oxide synthase-1: insight into mechanism of inhibition by type II ligand imidazole

  • Yoeun, Sereyvath;Rakwal, Randeep;Han, Oksoo
    • BMB Reports
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    • v.46 no.3
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    • pp.151-156
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    • 2013
  • Phylogenetic and amino acid sequence analysis indicated that rice allene oxide synthase-1 (OsAOS1) is CYP74, and is clearly distinct from CYP74B, C and D subfamilies. Regio- and stereo-chemical analysis revealed the dual substrate specificity of OsAOS1 for (cis,trans)-configurational isomers of 13(S)- and 9(S)-hydroperoxyoctadecadienoic acid. GC-MS analysis showed that OsAOS1 converts 13(S)- and 9(S)-hydroperoxyoctadecadi(tri)enoic acid into their corresponding allene oxide. UV-Visible spectral analysis of native OsAOS1 revealed a Soret maximum at 393 nm, which shifted to 424 nm with several clean isobestic points upon binding of OsAOS1 to imidazole. The spectral shift induced by imidazole correlated with inhibition of OsAOS1 activity, implying that imidazole may coordinate to ferric heme iron, triggering a heme-iron transition from high spin state to low spin state. The implications and significance of a putative type II ligand-induced spin state transition in OsAOS1 are discussed.

First record of Brachaluteres ulvarum (Tetraodontiformes: Monacanthidae) from Jeju-do Island, southern Korea

  • Myoung, Se Hun;Park, Joo Myun;Lee, Hyo Jin;Jawad, Laith A.
    • Fisheries and Aquatic Sciences
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    • v.24 no.6
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    • pp.228-234
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    • 2021
  • A single specimen (39.4 mm standard length) of Brachaluteres ulvarum, belonging to the family Monacanthidae has been recorded for the first time from Supseom, Jeju-do Island of southern Korea on 6 March 2021. This species was characterized by the presence of a small second dorsal spine present, the posterior end of pelvic without encasing scales, and numerous thin dark longitudinal lines on body. It was morphologically similar to the B. taylori, but distinguished by the ratio of the caudal peduncle to the head length (B. ulvarum, 2.5 to 3.7 times; B. taylori, 3.5 to 5.2 times). In addition, the former is well distinguished from the latter through mitochondrial cytochrome c oxidase subunit I (COI) sequences by genetic distances of range from 0.088 to 0.090. The new Korean name "Kko-ma-jwi-chi- sog" is proposed for the genus Brachaluteres, and "Kko-ma-jwi-chi" for the species B. ulvarum.

Phylogeography of Gloiopeltis furcata sensu lato (Gigartinales, Rhodophyta) provides the evidence of glacial refugia in Korea and Japan

  • Yang, Mi Yeon;Fujita, Daisuke;Kim, Myung Sook
    • ALGAE
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    • v.36 no.1
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    • pp.13-24
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    • 2021
  • The present-day genetic structure of macroalgal species reflects both geographical history and oceanic circulation patterns as well as anthropogenic introduction across native ranges. To precisely understand the genetic diversity and how the factors shape the current population structure of Gloiopeltis furcata sensu lato, we determined the mitochondrial 5' end of cytochrome c oxidase subunit I (COI-5P) sequences for 677 individuals sampled from 67 sites spanning almost the entire distribution range in Korea and Japan. Results from the phylogenetic analysis and haplotype distribution revealed eleven distinct lineages within G. furcata s.l. along the Korea-Japan coastal areas and displayed divergent phylogeographic patterns among lineages. Despite the closely related lineages distributed in same habitats as high rocky intertidal zone, they display different phylogeographic patterns among lineages. The populations from the south of Korea-Japan harbored the highest genetic diversity and unique endemism in comparison with other populations in the distribution range. This could be the evidence of southern refugia for G. furcata s.l. in the Northwest (NW) Pacific and the recent migration from native to introduced region. The reason is that an exceptional distribution pattern was found high genetic diversity in Hakodate of Japan where is the northern location in the NW Pacific. Our results imply the contemporary influence on the distribution due to current circulation pattern and anthropogenic effects. These phylogeographic findings provide the important insight into cryptic species diversity and the detailed distribution pattern of Gloiopeltis in the NW Pacific.