• 제목/요약/키워드: Stress-inducing factor

검색결과 58건 처리시간 0.029초

Gartanin enhances TRAIL-mediated liver cancer cell death through DR5 upregulation and autophagy activation

  • Dong-Oh Moon
    • Journal of Applied Biological Chemistry
    • /
    • 제66권
    • /
    • pp.53-59
    • /
    • 2023
  • Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has no effect on normal cells, but selectively can induce apoptosis in tumor cells. Gartanin, a xanthone compound in mangosteen, has been shown to inhibit cancer cell growth by arresting the cell cycle and inducing autophage. In this study, we revealed that gartanin can sensitize TRAIL-induced human liver cancer cell death. We also found that gartanin enhances DR5 expression, a death receptor for TRAIL. This effect appears to be related to CHOP activation associated with the response of endoplasmic reticulum stress. Gartanin treatment also inhibited p62 protein expression and cleaved LC3 to activate autophagy flux, which is related with TRAIL-induced cell death. Pretreatment with autophagy flux inhibitor, LY294002, inhibited gartanin-induced DR5 expression. In summary, our results reveal that the combined treatment of gartanin and TRAIL can be a valuable tool for cancer treatment.

MiT Family Transcriptional Factors in Immune Cell Functions

  • Kim, Seongryong;Song, Hyun-Sup;Yu, Jihyun;Kim, You-Me
    • Molecules and Cells
    • /
    • 제44권5호
    • /
    • pp.342-355
    • /
    • 2021
  • The microphthalmia-associated transcription factor family (MiT family) proteins are evolutionarily conserved transcription factors that perform many essential biological functions. In mammals, the MiT family consists of MITF (microphthalmia-associated transcription factor or melanocyte-inducing transcription factor), TFEB (transcription factor EB), TFE3 (transcription factor E3), and TFEC (transcription factor EC). These transcriptional factors belong to the basic helix-loop-helix-leucine zipper (bHLH-LZ) transcription factor family and bind the E-box DNA motifs in the promoter regions of target genes to enhance transcription. The best studied functions of MiT proteins include lysosome biogenesis and autophagy induction. In addition, they modulate cellular metabolism, mitochondria dynamics, and various stress responses. The control of nuclear localization via phosphorylation and dephosphorylation serves as the primary regulatory mechanism for MiT family proteins, and several kinases and phosphatases have been identified to directly determine the transcriptional activities of MiT proteins. In different immune cell types, each MiT family member is shown to play distinct or redundant roles and we expect that there is far more to learn about their functions and regulatory mechanisms in host defense and inflammatory responses.

터널 편압 대책에 대한 수치해석적 연구 (A Study of Numerical Analysis for Uneven Stress of Tunnel)

  • 현기환;윤지선
    • 한국지반공학회:학술대회논문집
    • /
    • 한국지반공학회 2000년도 가을 학술발표회 논문집
    • /
    • pp.501-508
    • /
    • 2000
  • In recent years, as lines are selected In disadvantageous region, unavoidable developments is increased. Owing to such developments. environmental problems have been occurred frequently, In excavation of tunnels especially located in close to slope, uneven stress take place to tunnel due to a topographical factor. it is used assistant methods of construction which are excavation of slope, retaining wall, ground anchor, etc for uneven stress. these assistant methods raise problems of environmental. In this study, using slit, we could make better stress state by means of inducing stress concentration in boundary of tunnel. considering a variety of slit and rock mass condition, we use numerical analysis.

  • PDF

Fat Mass and Obesity-Associated (FTO) Stimulates Osteogenic Differentiation of C3H10T1/2 Cells by Inducing Mild Endoplasmic Reticulum Stress via a Positive Feedback Loop with p-AMPK

  • Son, Hyo-Eun;Min, Hyeon-Young;Kim, Eun-Jung;Jang, Won-Gu
    • Molecules and Cells
    • /
    • 제43권1호
    • /
    • pp.58-65
    • /
    • 2020
  • Fat mass and obesity-associated (FTO) gene helps to regulate energy homeostasis in mammals by controlling energy expenditure. In addition, FTO functions in the regulation of obesity and adipogenic differentiation; however, a role in osteogenic differentiation is unknown. This study investigated the effects of FTO on osteogenic differentiation of C3H10T1/2 cells and the underlying mechanism. Expression of osteogenic and endoplasmic reticulum (ER) stress markers were characterized by reverse-transcriptase polymerase chain reaction and western blotting. Alkaline phosphatase (ALP) staining was performed to assess ALP activity. BMP2 treatment increased mRNA expression of osteogenic genes and FTO. Overexpression of FTO increased expression of the osteogenic genes distal-less homeobox5 (Dlx5) and runt-related transcription factor 2 (Runx2). Activation of adenosine monophosphate-activated protein kinase (AMPK) increased FTO expression, and there was a positive feedback loop between FTO and p-AMPK. p-AMPK and FTO induced mild ER stress; however, tunicamycin-induced severe ER stress suppressed FTO expression and AMPK activation. In summary, FTO induces osteogenic differentiation of C3H10T1/2 cells upon BMP2 treatment by inducing mild ER stress via a positive feedback loop with p-AMPK. FTO expression and AMPK activation induce mild ER stress. By contrast, severe ER stress inhibits osteogenic differentiation by suppressing FTO expression and AMPK activation.

Hypoxic repression of CYP7A1 through a HIF-1α- and SHP-independent mechanism

  • Moon, Yunwon;Park, Bongju;Park, Hyunsung
    • BMB Reports
    • /
    • 제49권3호
    • /
    • pp.173-178
    • /
    • 2016
  • Liver cells experience hypoxic stress when drug-metabolizing enzymes excessively consume O2 for hydroxylation. Hypoxic stress changes the transcription of several genes by activating a heterodimeric transcription factor called hypoxia-inducible factor-1α/β (HIF-1α/β). We found that hypoxic stress (0.1% O2) decreased the expression of cytochrome P450 7A1 (CYP7A1), a rate-limiting enzyme involved in bile acid biosynthesis. Chenodeoxycholic acid (CDCA), a major component of bile acids, represses CYP7A1 by activating a transcriptional repressor named small heterodimer partner (SHP). We observed that hypoxia decreased the levels of both CDCA and SHP, suggesting that hypoxia repressed CYP7A1 without inducing SHP. The finding that overexpression of HIF-1α increased the activity of the CYP7A1 promoter suggested that hypoxia decreased the expression of CYP7A1 in a HIF-1-independent manner. Thus, the results of this study suggested that hypoxia decreased the activity of CYP7A1 by limiting its substrate O2, and by decreasing the transcription of CYP7A1.

Redox-Dependent Modulation of RsrA, an Anti-Sigma Factor Regulating Thioredoxin Operons in Streptomyces coelicolor

  • Bae, Jae-Bum;Park, Joo-Hong;Roe, Jung-Hye
    • 한국생물물리학회:학술대회논문집
    • /
    • 한국생물물리학회 2002년도 제9회 학술 발표회 프로그램과 논문초록
    • /
    • pp.54-54
    • /
    • 2002
  • $\sigma$$\^$R/ is a sigma factor responsible for inducing the thioredoxin system in response to oxidative stress in Streptomyces coelicolor. RsrA, an anti-sigma factor, specifically binds to $\sigma$$\^$R/ and inhibits $\sigma$$\^$R/-directed transcription under reducing conditions. Exposure to H$_2$O$_2$ or thiol-specific oxidant diamide dissociates $\sigma$$\^$R/-RsrA complex. The redox-dependent regulation of $\sigma$$\^$R/-RsrA binding has been reported to involve thiol-disulfide exchange in RsrA, which contains 7 cysteines in 105 amino acid residues.(omitted)

  • PDF

Two distinct nodes of translational inhibition in the Integrated Stress Response

  • Ryoo, Hyung Don;Vasudevan, Deepika
    • BMB Reports
    • /
    • 제50권11호
    • /
    • pp.539-545
    • /
    • 2017
  • The Integrated Stress Response (ISR) refers to a signaling pathway initiated by stress-activated $eIF2{\alpha}$ kinases. Once activated, the pathway causes attenuation of global mRNA translation while also paradoxically inducing stress response gene expression. A detailed analysis of this pathway has helped us better understand how stressed cells coordinate gene expression at translational and transcriptional levels. The translational attenuation associated with this pathway has been largely attributed to the phosphorylation of the translational initiation factor $eIF2{\alpha}$. However, independent studies are now pointing to a second translational regulation step involving a downstream ISR target, 4E-BP, in the inhibition of eIF4E and specifically cap-dependent translation. The activation of 4E-BP is consistent with previous reports implicating the roles of 4E-BP resistant, Internal Ribosome Entry Site (IRES) dependent translation in ISR active cells. In this review, we provide an overview of the translation inhibition mechanisms engaged by the ISR and how they impact the translation of stress response genes.

Regulation of Apoptosis by Nitrosative Stress

  • Kim, Ki-Mo;Kim, Peter K.M.;Kwon, Young-Guen;Bai, Se-Kyung;Nam, Woo-Dong;Kim, Young-Myeong
    • BMB Reports
    • /
    • 제35권1호
    • /
    • pp.127-133
    • /
    • 2002
  • Nitrosative stress can prevent or induce apoptosis. It occurs via S-nitrosylation by the interaction of nitric oxide (NO) with the biological thiols of proteins. Cellular redox potential and non-heme iron content determine S-nitrosylation. Apoptotic cell death is inhibited by S-nitrosylation of the redox-sensitive thiol in the catalytic site of caspase family proteases, which play an essential role in the apoptotic signal cascade. Nitrosative stress can also promote apoptosis by the activation of mitochondrial apoptotic pathways, such as the release of cytochrome c, an apoptosis-inducing factor, and endonuclease G from mitochondria, as well as the suppression of NF-${\kappa}B$ activity. In this article we reviewed the mechanisms whereby S-nitrosylation and nitrosative stress regulate the apoptotic signal cascade.

Chronic cold stress-induced myocardial injury: effects on oxidative stress, inflammation and pyroptosis

  • Hongming Lv;Yvxi He;Jingjing Wu; Li Zhen ;Yvwei Zheng
    • Journal of Veterinary Science
    • /
    • 제24권1호
    • /
    • pp.2.1-2.14
    • /
    • 2023
  • Background: Hypothermia is a crucial environmental factor that elevates the risk of cardiovascular disease, but the underlying effect is unclear. Objectives: This study examined the role of cold stress (CS) in cardiac injury and its underlying mechanisms. Methods: In this study, a chronic CS-induced myocardial injury model was used; mice were subjected to chronic CS (4℃) for three hours per day for three weeks. Results: CS could result in myocardial injury by inducing the levels of heat shock proteins 70 (HSP70), enhancing the generation of creatine phosphokinase-isoenzyme (CKMB) and malondialdehyde (MDA), increasing the contents of tumor necrosis factor-α (TNF-α), high mobility group box 1 (HMGB1) interleukin1b (IL-1β), IL-18, IL-6, and triggering the depletion of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH). Multiple signaling pathways were activated by cold exposure, including pyroptosis-associated NOD-like receptor 3 (NLRP3)-regulated caspase-1-dependent/Gasdermin D (GSDMD), inflammation-related toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)-mediated nuclear factor kappa B (NF-κB), and mitogen-activated protein kinase (MAPK), as well as oxidative stressinvolved thioredoxin-1/thioredoxin-interacting protein (Txnip) signaling pathways, which play a pivotal role in myocardial injury resulting from hypothermia. Conclusions: These findings provide new insights into the increased risk of cardiovascular disease at extremely low temperatures.

일반 진료 치과의사와 소아 진료 치과의사의 스트레스 유발 요인과 직무 스트레스 정도에 대한 연구 (Investigation of Stress-Inducing Factors and Occupational Stress Levels in General and Pediatric Dentists)

  • 김승현;이제식
    • 대한소아치과학회지
    • /
    • 제49권4호
    • /
    • pp.481-496
    • /
    • 2022
  • 이번 연구는 소아 환자를 치료할 때 소아 진료 치과의사와 일반 진료 치과의사들에게 스트레스를 유발하는 원인과 직무 스트레스 정도에 대해 알아보고자 하였으며 66명의 소아진료 치과의사와 125명의 일반 진료 치과의사, 총 191명의 연구대상자를 통해 평가하였다. 소아 환자 치료 시 2개의 군 모두 환자의 협조도 부족에 의해 가장 높은 스트레스를 느꼈으며 이외에도 예후의 불확실성과 낮은 수가, 보호자의 협조도 부족 등에 의해 스트레스를 나타내었다. 또한 보호자의 협조도 부족과 예후의 불확실성에 의해 소아 진료 치과의사가 일반 진료 치과의사보다 유의하게 높은 스트레스를 받고 있었다(p < 0.05). 전반적 직무스트레스는 2개의 군 모두 환자, 시간, 직무 환경, 수입 관련 스트레스 순으로 높았으며 소아 진료 치과의사의 스트레스 정도가 더 낮았다. 직업적 번아웃은 '냉소주의'에서 2개의 군 모두 98% 이상이 번아웃을 보였으며 '정서적 소진'은 69% 이상이 번아웃을 보여 그 비율이 매우 높았다. 또한 '성취감 저하'는 번아웃의 비율이 낮았으며 소아 진료 치과의사가 일반 진료 치과의사에 비해 통계적으로 유의하게 높은 성취감을 나타내었다(p < 0.05). 이번 연구를 통해 2개의 군 모두 높은 직무 스트레스를 보였으며 이를 완화하기 위한 노력이 필요하다.