• 제목/요약/키워드: loss of heme

검색결과 30건 처리시간 0.035초

HO-1 Induced by Cilostazol Protects Against TNF-${\alpha}$-associated Cytotoxicity via a PPAR-${\gamma}$-dependent Pathway in Human Endothelial Cells

  • Park, So-Youn;Bae, Jin-Ung;Hong, Ki-Whan;Kim, Chi-Dae
    • The Korean Journal of Physiology and Pharmacology
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    • 제15권2호
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    • pp.83-88
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    • 2011
  • A large body of evidence has indicated that induction of endogenous antioxidative proteins seems to be a reasonable strategy for delaying the progression of cell injury. In our previous study, cilostazol was found to increase the expression of the antioxidant enzyme heme oxygenase-1 (HO-1) in synovial cells. Thus, the present study was undertaken to examine whether cilostazol is able to counteract tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$)-induced cell death in endothelial cells via the induction of HO-1 expression. We exposed human umbilical vein endothelial cells (HUVECs) to TNF-${\alpha}$ (50 ng/ml), with or without cilostazol ($10{\mu}M$). Pretreatment with cilostazol markedly reduced TNF-${\alpha}$-induced viability loss in the HUVECs, which was reversed by zinc protoporphyrine IX (ZnPP), an inhibitor of HO-1. Moreover, cilostazol increased HO-1 protein and mRNA expression. Cilostazol-induced HO-1 induction was markedly attenuated not only by ZnPP but also by copper-protoporphyrin IX (CuPP). In an assay measuring peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) transcription activity, cilostazol directly increased PPAR-${\gamma}$ transcriptional activity which was completely abolished by HO-1 inhibitor. Furthermore, increased PPAR-${\gamma}$ activity by cilostazol and rosiglitazone was completely abolished in cells transfected with HO-1 siRNA. Taken together, these results indicate that cilostazol up-regulates HO-1 and protects cells against TNF-${\alpha}$-induced endothelial cytotoxicity via a PPAR-${\gamma}$-dependent pathway.

H2O2로 유발된 C6 신경교세포 사멸에 대한 총명공진단의 보호 효과 (Protective Effects of Chongmyunggongjin-dan on H2O2-induced C6 Glial Cell Death)

  • 황규상;신용진
    • 대한한방내과학회지
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    • 제41권1호
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    • pp.44-58
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    • 2020
  • Objectives: This study was conducted to identify the protective effects of Chongmyunggongjin-dan (CMGJD) on Hydrogen peroxide (H2O2)-induced apoptosis mechanisms in C6 glial cells. Method: We used CMGJD after distilled water extraction, filtration, and lyophilization. The ROS scavenging effect was examined by fluorescence microscopy. Expression levels of proteins related to ROS generation were investigated by western blotting. Functional changes in organelles related to Reactive oxygen species (ROS) generation were investigated by immunoblotting and by verifying expression level of relevant enzymes. Results: The CMGJD extract protected the cells against H2O2-induced morphological changes and DNA fragmentation, inhibited the increase of Heme_oxygenase-1(HO-1) and the decrease in catalase, protected against the loss of mitochondrial membrane potential, inhibited disturbances of lysosomal function, and induced an increase in peroxisomes. Conclusion: CMGJD was confirmed to have a protective effect on H2O2-induced C6 glial cell death possibly by blocking the pathways causing damage to subcellular organelles, such as mitochondria, lysosomes, and peroxisomes. We assume that CMGJD will be effective for the prevention and treatment of ischemic stroke in a clinical environment.

토끼고기의 영양성분 및 품질특성 평가 (Evaluation of the Nutritional Composition and Quality Traits of Rabbit Meat)

  • 이정아;정숙한;설국환;김현욱;조수현;강선문
    • 한국식생활문화학회지
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    • 제37권2호
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    • pp.171-177
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    • 2022
  • This study evaluated the nutritional composition and quality traits of rabbit meat as compared to chicken meat. Samples of loin (M. longissimus dorsi) and breast meats were collected from rabbit and chicken carcasses, respectively. The meats were then analyzed for the proximate composition, collagen and energy contents, fatty acid composition, myoglobin and heme iron contents, pH value, water-holding capacity (WHC), cooking loss, meat color, Warner-Bratzler shear force (WBSF) value, and texture profile. Compared to chicken breast meat, lower (p<0.05) protein content and higher (p<0.05) ash and collagen contents were obtained in rabbit loin meat. Rabbit meat remarkably had higher (p<0.05) total polyunsaturated fatty acids (PUFA) and linolenic acid contents and lower (p<0.05) n-6/n-3 PUFA ratio as compared to chicken meat. The pH value and WHC were lower (p<0.05) in rabbit meat than in chicken meat (p<0.05). Rabbit meat exhibited lower (p<0.05) L* value and higher (p<0.05) a* and b* values compared to chicken meat (p<0.05). The WBSF value, hardness, and gumminess were higher (p<0.05) in rabbit meat than in chicken meat (p<0.05). These findings suggest that rabbit meat has higher essential n-3 PUFA, darker color, and firmer texture as compared to chicken meat.

A New Sterol Regulatory Element Binding Protein, SrbB Is Critical for Hypoxia Adaptation and Virulence in the Human Fungal Pathogen Aspergillus fumigatus

  • Chung, Dawoon;Barker, Bridget M.;Carey, Charles C.;Merriman, Brittney;Werner, Ernst R.;Lechner, Beatrix E.;Dhingra, Sourabh;Cheng, Chao;Xu, Wenjie;Blosser, Sara J.;Morohashi, Kengo;Mazurie, Aurelien;Mitchell, Thomas K.;Haas, Hubertus;Mitchell, Aaron P.;Cramer, Robert A.
    • 한국균학회소식:학술대회논문집
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    • 한국균학회 2015년도 춘계학술대회 및 임시총회
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    • pp.15-15
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    • 2015
  • Aspergillus fumigatus is a major cause of invasive aspergillosis (IA), a significant health issue worldwide with high mortality rates up to 95%. Our lab is interested in how A. fumigatus adapts to low oxygen conditions 'hypoxia', which is one of the important host microenvironments. A. fumigatus SrbA is a basic helix-loop-helix (bHLH) transcriptional regulator and belongs to sterol regulatory element binding protein (SREBP) family members. Loss of SrbA completely blocks growth in hypoxia and results in avirulence in murine models of IA suggesting an essential role of SrbA in hypoxia adaptation and virulence in A. fumigatus. We conducted chromatin immunoprecipitation sequencing (ChIP-seq) with A. fumigatus wild type using a SrbA specific antibody, and 97 genes were revealed as SrbA direct targets. One of the 'SrbA regulons' (AFUB_099590) was a putative bHLH transcriptional regulator whose sequence contained a characteristic tyrosine substitution in the basic portion of the bHLH domain of SREBPs. Therefore, we designated AFUB_099590 SrbB. Further characterization of SrbB demonstrated that SrbB is important for radial growth, biomass production, and biosynthesis of heme intermediates in hypoxia and virulence in A. fumigatus. A series of quantitative real time PCR showed that transcription of several SrbA regulons is coordinately regulated by two SREBPs, SrbA and SrbB in hypoxia. This suggests that SrbA and SrbB have both dependent and independent functions in regulation of genes responsible for hypoxia adaptation in A. fumigatus. Together, our data provide new insights into complicated roles of SREBPs in adaptation of host environments and virulence in pathogenic fungi.

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Protective effects skin keratinocyte of Oenothera biennis on hydrogen peroxide-induced oxidative stress and cell death via Nrf2/Ho1 pathway.

  • Lee, Seung Young;Jung, Ji Young;Choi, Hee Won;Choi, Kyung Min;Jeong, Jin-Woo
    • 한국자원식물학회:학술대회논문집
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    • 한국자원식물학회 2018년도 추계학술대회
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    • pp.103-103
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    • 2018
  • Oenothera biennis, commonly known as evening primrose, a potential source of natural bioactive substances: flavonoids, steroids, tannins, fatty acids and terpenoids responsible for a diverse range of pharmacological functions. However, whether extract prepared from aerial part of O. biennis (APOB) protects skin against oxidative stress remains unknown. To investigate the protective effects of APOB against oxidative stress-induced cellular damage and elucidated the underlying mechanisms in the HaCaT human skin keratinocytes. Our results revealed that treatment with APOB prior to hydrogen peroxide ($H_2O_2$) exposure significantly increased viability, and the highest DPPH radical-scavenging activities and reducing power of HaCaT cells. APOB also effectively attenuated H2O2-induced comet tail formation and inhibited the $H_2O_2$-induced phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V-positive cells. In addition, APOB exhibited scavenging activity against intracellular reactive oxygen species (ROS) accumulation and restored the mitochondrial membrane potential loss by $H_2O_2$. Moreover, $H_2O_2$ enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase (PARP), a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with APOB. Furthermore, APOB increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, APOB is able to protect HaCaT cells from $H_2O_2$-induced DNA damage and cell death through blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating the Nri2/HO-1 signaling pathway.

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인체 신경세포에서 청뇌명신환(淸腦明神丸)의 산화적 스트레스에 대한 세포보호 효과 (Neuroprotective Effects of Cheongnoemyeongsin-hwan against Hydrogen Peroxide-induced DNA Damage and Apoptosis in Human Neuronal-Derived SH-SY5Y Cells)

  • 피국현;황원덕
    • 대한한의학방제학회지
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    • 제25권1호
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    • pp.51-68
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    • 2017
  • Objectives : Oxidative stress due to excessive accumulation of reactive oxygen species (ROS) is one of the risk factors for the development of several chronic diseases, including neurodegenerative diseases. Methods : In the present study, we investigated the protective effects of cheongnoemyeongsin-hwan (CNMSH) against oxidative stress‑induced cellular damage and elucidated the underlying mechanisms in neuronal-derived SH-SY5Y cells. Results : Our results revealed that treatment with CNMSH prior to hydrogen peroxide (H2O2) exposure significantly increased the SH-SY5Y cell viability, indicating that the exposure of the SH-SY5Y cells to CNMSH conferred a protective effect against oxidative stress. CNMSH also effectively attenuated H2O2‑induced comet tail formation, and decreased the phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V‑positive cells. In addition, CNMSH exhibited scavenging activity against intracellular ROS generation and restored the mitochondria membrane potential (MMP) loss that were induced by H2O2, suggesting that CNMSH prevents H2O2‑induced DNA damage and cell apoptosis. Moreover, H2O2 enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase, a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with CNMSH. Furthermore, CNMSH increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, CNMSH is able to protect SH-SY5Y cells from H2O2-induced apoptosis throughout blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating Nrf2/HO-1 signaling pathway. Conclusions : Therefore, we believed that CNMSH may potentially serve as an agent for the treatment and prevention of neurodegenerative diseases caused by oxidative stress.

디엘드린 유도성 소포체 스트레스에서의 parkin과 Bcl-2의 신경보호 효과 (Neuroprotective Effects of Parkin and Bcl-2 against Dieldrin-induced Endoplasmic Reticulum Stress)

  • 서정연;김재성;김도경;전홍성
    • 생명과학회지
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    • 제32권10호
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    • pp.771-777
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    • 2022
  • 파킨슨병에서의 도파민 신경세포의 사멸 원인은 다양하며 별개의 유전적 요소와 환경적 요소들이 관여한다. 드물게 발생하는 유전성 파킨슨병에서 parkin의 돌연변이와 기능 상실은 주로 소포체 스트레스를 통해 중뇌 흑질의 도파민 신경세포를 특이적으로 손상시킨다. 상대적으로 일반적인 특발성 파킨슨병에서는 살충제 노출이 역학적으로 중요하다. 그러나 환경독성물질에의 노출과 유전성 파킨슨병의 연관성에 대해서는 잘 알려진 바가 없다. 본 연구에서는 잘 확립된 중뇌 유래의 도파민 신경세포주인 N27-A를 사용하여 특발성 파킨슨병과 유전성 파킨슨병 사이의 공통된 발병 기작의 증거를 확인하였다. 특발성 파킨슨병을 유발하는 유기염소계 살충제인 디엘드린은 BiP/Grp78, 헴산화효소-1과 같은 소포체 스트레스 반응 표지자를 발현 유도하였고, 특히 parkin 단백질의 발현을 증가시켰다. 디엘드린이 N27-A 세포를 사멸시키는 과정에서 소포체 스트레스 특이적 세포사를 매개하는 Caspase-12의 활성화가 유의미하게 증가하였다. 흥미롭게도 디엘드린에 의한 N27-A 세포의 사멸이 소포체 단백질인 parkin과 Bcl-2의 과발현시 유의미하게 억제되었다. 본 연구 결과, 소포체 스트레스의 누적이 특발성, 유전성 파킨슨병의 공통의 발병 기작일 가능성이 있으며, 몇 가지 소포체 관련 단백질들이 디엘드린에 의한 도파민 신경세포 손상으로부터 보호 효과를 가지는 것으로 보인다.

HT22 해마세포의 oxidative toxicity에 대한 천문동 유래 에탄올추출물의 보호 효과 (Ethanol Extract from Asparagus Cochinchinensis Attenuates Glutamate-Induced Oxidative Toxicity in HT22 Hippocampal Cells)

  • 박맑은;최병태
    • 생명과학회지
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    • 제26권12호
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    • pp.1458-1465
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    • 2016
  • 본 연구는 oxidative stress에 의한 세포죽음 분석의 이상적인 모델로 사용되는 HT22세포를 이용하여 천문동 에탄올추출물의 glutamate에 의한 oxidative toxicity에 대한 신경보호 효과를 살펴보았다. 이를 위해 cell viability, lactate dehydrogenase (LDH), 그리고 세포죽음형태, reactive oxygen species (ROS), mitochondria membrane potential (MMP) 등에 대한 flow cytometry 및 Western blot분석을 이용하였다. 천문동 추출물의 처리는 cell viability 및 LDH분석에서 glutamate에 의한 cell toxicity를 저하시키며, 특히 apoptotic cell death를 현저히 감소시켰다. ROS 및 MMP분석 결과, 천문동 추출물은 ROS의 형성을 저하시키며 glutamate에 의해 저하된 MMP를 현저히 회복시켜 주었다. 이와 관련된 단백질 발현을 보면, 천문동 추출물은 PARP 및 HO-1의 발현을 억제하였다. 이상의 결과는 천문동 추출물이 HT22해마세포에서 ROS형성저해 및 MMP회복에 의해 세포죽음을 완화시켜 보호작용을 하는 것으로 사료되며 oxidative toxicity관련 질환에 적용 가능할 것으로 보여 진다.

돼지 품종의 교배조합간 육질특성 비교 (Comparison of Meat Quality Characteristics between Crossbreeds)

  • 오하식;김현열;양한술;이정일;주영국;김철욱
    • 한국축산식품학회지
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    • 제28권2호
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    • pp.171-180
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    • 2008
  • 비육돈 생산에 있어 교배조합이 육질특성에 미치는 영향을 알아보고자 $LY{\times}D$, $Y{\times}B$$L{\times}B$ 품종을 이용하여 조사하였다. 교배조합별 30두씩 공시, 출하평균 체중은 110-120 kg이며, 일괄적으로 부경양돈농협 김해공판장에서 도축하여 24시간동안 $-3^{\circ}C$의 예냉실에서 냉도체를 만든 후 돈육의 등심부위(5번 늑골-3번 요추사이)를 발골 정형하여 처리구당 개체 5반복하여 wrap으로 함기포장한 후 냉장온도($4^{\circ}C$)가 유지되는 boxer에 담아 경상대학교 식육가공연구실로 운반하여 돈육의 일반선분, 이화학적 특성분석(pH, 전단가, 육즙손실, 가열감량), 육색과 지방색, 조직감, 지방산화, 관능적 특성분석 및 지방산 조성 등을 조사하여 교배조합간 돈육 등심의 품질특성을 구명하고자 실시하였다. 등지방두께는 LYD그룹이 YB나 LB 그룹에 비하여 두꺼웠다. 육질평가에서 근내지방, 근간지방, 피하지방 및 탄력성은 교배조합간에 차이가 없었다. 육질특성에서 일반성분, pH, 육즙감량, 조리감량 및 가열육의 관능검사는 교배조합간에 유의적인 차이가 없었다. 전단가는 LB 그룹이 LYD나 YB그룹에 비하여 유의적으로 낮은 값을 보였다(p<0.05). 총 육색소 함량은 YB 그룹이 LYD와 LB 그룹에 비하여 유의적으로 높은 함량을 보였다(p<0.05). 지방산화(TBARS)는 YB 그룹이 저장 5일과 8일에 LYD 그룹에 비하여 유의적으로 낮은 값을 보였으며, 저장기간이 경과함에 따라 모든 교배조합이 유의적으로 증가하였다(p<0.05). 육색 중 L 간은 YB 그룹이 가장 낮았으며, a 값은 가장 높았다. 지방색은 반대로 L 값은 YB 그룹이 가장 높았으며, a 값은 가장 낮았다 조직감 중 경도와 부착성은 LB 그룹이 가장 높았으며(p<0.05), 응집성은 LYD 그룹이 가장 높았다(p<0.05). 신선육의 관능검사 중 육색은 YB 그룹이 LYD나 LB 그룹에 비하여 높은 점수를 받았다(p<0.05). 지방산 조성중 myristic acid(14:0) 함량은 LB 그룹이 가장 낮았으며, 반면에 arachidonic acid(20:4) 함량은 가장 높았다. 전체적으로 고찰하면 교배조합간의 육질 특성을 비교하였을 때 YB 품종이 가장 우수한 것으로 나타났다.

Conjugated Linoleic Acid(CLA)가 축적된 돈육의 저장기간중 이화학적 특성변화 (Changes of Physicochemical Properties of Conjugated Linoleic Acid(CLA) Accumulated Pork during Storage Time)

  • 이정일;정재두;이진우;이제룡;정진연;양한술;주선태
    • 한국축산식품학회지
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    • 제23권3호
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    • pp.236-249
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    • 2003
  • Conjugated linoleic acid(CLA)를 비육돈에 급여하여 비육돈체조직내에 CLA를 축적시키고, CLA가 축적된 돈육의 품질 특성에 대한 연구를 수행하였다. 대조구는 80∼110 kg 까지는 일반사료회사에서 생산하는 사료를 급여하였으며, 처리구 1은 출하(출하체중: 110 kg) 2주전부터 일반사료회사에서 생산하는 사료에 CLA를 1.25% 첨가하여 급여하였으며, 처리구2는 출하 2주전부터 사료함량에 CLA를 2.5% 첨가하여 급여하였다. 처리구 3은 사료함량에 1.25% CLA를 첨가하여 4주간 급여하였으며, 처리구 4는 2.5% CLA를 4주간 급여하였다. 급여기간이 끝난 후 일괄적으로 함양도축장에서 도축하여 돈육의 등심부위를 함기포장하여 냉장온도(4'E)에서 14일간 저장하면서 각 실험항목을 조사하였다 저장기간에 따른 돈육등심의 일반성분, 이화학적 특성 및 관능평가등을조사하여 CLA가 축적된 돈육의 저장기간에 따른 품질특성을 규명하고자 하였다. pH변화를 보면 전 저장기간동안 대조구에 비하여 CLA 급여 처리구가 유의적으로 높은 pH를 보여(p<0.05) CLA 급여가 PH 변화에 영향을 미치는 것으로 나타났다. 저장기간에 따른 pH 변화에서 모든 처리구가 저장기간이 경과함에 따라 pH가 증가하는 경향을 보였다. CLA급여 수준과 급여기간이 등심근내 조지방 함량에는 유의적인 영향을 미치는 것으로 나타났으며(p<0.05), 대조구와 CLA 급여처리구간에는 대조구에 비하여 CLA급여 처리구가 높은 조지방 함량을 보였다(p<0.05). 보수성은 대조구에 비하여 CLA 급여 처리구가 높은 경향을 보였다. 저장 초기에는 대조구에 비하여 CLA 급여 처리구가 유의적으로(p<0.05) 낮은 육즙손실을 보였으며, 모든 처리구가 저장기간이 경과함에 따라 육즙손실이 유의적으로 감소하는 경향을 보였다. CLA 급여수준과 급여기간이 육색과 총육색소 함량에는 영향을 미치지 않는 것으로 나타났다. 관능적 특성평가 중 육색과 육즙참출은 대조구와 비교하여 CLA급여 처리구가 유의적인 차이가 없었으나, 근내지방 축적 정도와 전체적인 기호성은 대조구에 비하여 CLA 급여 처리구가 유의적으로 높은 평가를 받았다(p<0.05).