• BMB Reports
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• 제48권7호
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• pp.369-370
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• 2015

Actin dynamics is critical for the formation and sustainment of the immunological synapse (IS) during T cell interaction with antigen-presenting cells (APC). Thus, many actin regulating proteins are involved in spatial and temporal actin remodeling at the IS. However, little is known whether or how actin stabilizing protein controls IS and the consequent T cell functions. TAGLN2 − an actin-binding protein predominantly expressed in T cells − displays a novel function to stabilize cortical F-actin, thereby augmenting F-actin contents at the IS, and acquiring leukocyte function-associated antigen-1 activation following T cell activation. TAGLN2 also competes with cofilin to protect F-actin in vitro and in vivo. During cytotoxic T cell interaction with cancer cells, the expression level of TAGLN2 at the IS correlates with the T cell adhesion to target cancer cells and production of lytic granules such as granzyme B and perforin, thus expressing cytotoxic T cell function. These findings identify a novel function for TAGLN2 as an actin stabilizing protein that is essential for stable immunological synapse formation, thereby regulating T cell immunity. [BMB Reports 2015; 48(7): 369-370]

• IMMUNE NETWORK
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• 제10권5호
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• pp.153-163
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• 2010

Background: In addition to TCR and costimulatory signals, cytokine signals are required for the differentiation of activated CD8 T cells into memory T cells and their survival. Previously, we have shown that IL-12 priming during initial antigenic stimulation significantly enhanced the survival of activated CD8 T cells and increased the memory cell population. In the present study, we analyzed the mechanisms by which IL-12 priming contributes to activation and survival of CD8 T cells. Methods: We observed dramatically decreased expression of CD43 in activated CD8 T cells by IL-12 priming. We purified $CD43^{lo}$ and $CD43^{hi}$ cells after IL-12 priming and analyzed the function and survival of each population both in vivo and in vitro. Results: Compared to $CD43^{hi}$ effector cells, $CD43^{lo}$ effector CD8 T cells exhibited reduced cytolytic activity and lower granzyme B expression but showed increased survival. $CD43^{lo}$ effector CD8 T cells also showed increased in vivo expansion after adoptive transfer and antigen challenge. The enhanced survival of $CD43^{lo}$ CD8 T cells was also partly associated with CD62L expression. Conclusion: We suggest that CD43 expression regulated by IL-12 priming plays an important role in differentiation and survival of CD8 T cells.

• BMB Reports
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• 제56권3호
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• pp.184-189
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• 2023

Ovarian cancer (OC) is the most common gynecological malignancy worldwide, and chemoresistance occurs in most patients, resulting in treatment failure. A better understanding of the molecular processes underlying drug resistance is crucial for development of efficient therapies to improve OC patient outcomes. Circular RNAs (circRNAs) and ferroptosis play crucial roles in tumorigenesis and resistance to chemotherapy. However, little is known about the role(s) of circRNAs in regulating ferroptosis in OC. To gain insights into cisplatin resistance in OC, we studied the ferroptosis-associated circRNA circSnx12. We evaluated circSnx12 expression in OC cell lines and tissues that were susceptible or resistant to cisplatin using quantitative real-time PCR. We also conducted in vitro and in vivo assays examining the function and mechanism of lnc-LBCSs. Knockdown of circSnx12 rendered cisplatin-resistant OC cells more sensitive to cisplatin in vitro and in vivo by activating ferroptosis, which was at least partially abolished by downregulation of miR-194-5p. Molecular mechanics studies indicate that circSnx12 can be a molecular sponge of miR-194-5p, which targets SLC7A11. According to our findings, circSnx12 ameliorates cisplatin resistance by blocking ferroptosis via a miR-194-5p/SLC7A11 pathway. CircARNT2 may thus serve as an effective therapeutic target for overcoming cisplatin resistance in OC.

• BMB Reports
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• 제56권3호
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• pp.178-183
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• 2023

Huntington's disease (HD) is a neurodegenerative disorder, of which pathogenesis is caused by a polyglutamine expansion in the amino-terminus of huntingtin gene that resulted in the aggregation of mutant HTT proteins. HD is characterized by progressive motor dysfunction, cognitive impairment and neuropsychiatric disturbances. Histone deacetylase 6 (HDAC6), a microtubule-associated deacetylase, has been shown to induce transport- and release-defect phenotypes in HD models, whilst treatment with HDAC6 inhibitors ameliorates the phenotypic effects of HD by increasing the levels of α-tubulin acetylation, as well as decreasing the accumulation of mutant huntingtin (mHTT) aggregates, suggesting HDAC6 inhibitor as a HD therapeutics. In this study, we employed in vitro neural stem cell (NSC) model and in vivo YAC128 transgenic (TG) mouse model of HD to test the effect of a novel HDAC6 selective inhibitor, CKD-504, developed by Chong Kun Dang (CKD Pharmaceutical Corp., Korea). We found that treatment of CKD-504 increased tubulin acetylation, microtubule stabilization, axonal transport, and the decrease of mutant huntingtin protein in vitro. From in vivo study, we observed CKD-504 improved the pathology of Huntington's disease: alleviated behavioral deficits, increased axonal transport and number of neurons, restored synaptic function in corticostriatal (CS) circuit, reduced mHTT accumulation, inflammation and tau hyperphosphorylation in YAC128 TG mouse model. These novel results highlight CKD-504 as a potential therapeutic strategy in HD.

• Molecules and Cells
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• 제38권1호
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• pp.81-88
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• 2015

Flowering time (or heading date) is controlled by intrinsic genetic programs in response to environmental cues, such as photoperiod and temperature. Rice, a facultative short-day (SD) plant, flowers early in SD and late in long-day (LD) conditions. Casein kinases (CKs) generally act as positive regulators in many signaling pathways in plants. In rice, Heading date 6 (Hd6) and Hd16 encode $CK2{\alpha}$ and CKI, respectively, and mainly function to delay flowering time. Additionally, the major LD-dependent floral repressors Hd2/Oryza sativa Pseudo-Response Regulator 37 (OsPRR37;hereafter PRR37) and Ghd7 also confer strong photoperiod sensitivity. In floral induction, Hd16 acts upstream of Ghd7 and CKI interacts with and phosphorylates Ghd7. In addition, Hd6 and Hd16 also act upstream of Hd2. However, whether CKI and $CK2{\alpha}$ directly regulate the function of PRR37 remains unclear. Here, we use in vitro pull-down and in vivo bimolecular fluorescence complementation assays to show that CKI and $CK2{\alpha}$ interact with PRR37. We further use in vitro kinase assays to show that CKI and $CK2{\alpha}$ phosphorylate different regions of PRR37. Our results indicate that direct posttranslational modification of PRR37 mediates the genetic interactions between these two protein kinases and PRR37. The significance of CK-mediated phosphorylation for PRR37 and Ghd7 function is discussed.

• 한국음향학회지
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• 제39권5호
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• pp.435-440
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• 2020

음향집게는 마이크론 단위의 미세입자를 비접촉 방식으로 조작할 수 있어 다양한 생체공학 응용에 사용되고 있다. 현재까지 음향집게는 in vitro 실험을 목적으로 개발되어 임의파형 발생기와 전력 증폭기와 같은 부피가 큰 고가의 장비를 사용하여 구현하였다. 따라서 이러한 시스템은 이동이 불편하여 한정된 공간에서만 사용이 가능하기 때문에 향후 in vivo 및 임상 실험에 적합하지 않은 구조를 가진다. 따라서 본 논문에서는 이동이 가능한 휴대용 음향집게를 개발하고 그 성능을 평가하였다. 개발한 휴대용 음향집게 시스템은 하나의 Field Programmable Gate Array(FPGA)와 2 개의 펄서로 구현되었으며, Universal Serial Bus(USB) 통신을 이용하여 Personal Computer(PC)에서 송신 주파수 및 펄스 길이 등을 실시간으로 조절이 가능하도록 설계하였다. 개발한 시스템은 최대 20 MHz의 중심 주파수 까지 송신이 가능하며, 미세입자 및 세포를 포획할 수 있는 충분한 힘을 생성할 수 있었다. 개발한 시스템의 성능을 평가하기 위하여 40 ㎛와 90 ㎛ 크기의 폴리스티렌 입자를 포획 및 조정하였다.

• Biomolecules & Therapeutics
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• 제32권2호
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• pp.249-260
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• 2024

New supplements with preventive effects against skin photodamage are receiving increasing attention. This study evaluated the anti-photoaging effects of salmon nasal cartilage proteoglycan (SPG), acting as a functional material for skin health. We administered SPG to in vitro and in vivo models exposed to ultraviolet B (UVB) radiation and assessed its moisturizing and anti-wrinkle effects on dorsal mouse skin and keratinocytes and dermal fibroblasts cell lines. These results showed that SPG restored the levels of filaggrin, involucrin, and AQP3 in the epidermis of UVB-irradiated dorsal skin and keratinocytes, thereby enhancing the keratinization process and water flow. Additionally, SPG treatment increased the levels of hyaluronan and skin ceramide, the major components of intercellular lipids in the epidermis. Furthermore, SPG treatment significantly increased the levels of collagen and procollagen type 1 by down-regulating matrix metalloproteinase 1, which play a crucial role in skin fibroblasts, in both in vitro and in vivo models. In addition, SPG strongly inhibited mitogen-activated protein kinase (MAPKs) signaling, the including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. These findings suggest that dietary SPG may be an attractive functional food for preventing UVB-induced photoaging. And this SPG product may provide its best benefit when treating several signs of skin photoaging.

• 한국자원식물학회지
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• 제35권4호
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• pp.411-416
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• 2022

본 연구에서는 다양한 실험모델을 활용하여 참당귀 추출물의 면역조절 효능을 평가하였다. 특히 강제수영부하실험에서 참당귀 추출물의 경구투여는 부동시간의 감소 및 신장기능 지표인 BUN 및 근육의 피로관련 생화학적 지표인 LDH 활성 조절로 체력증진 효과를 나타내는 것으로 확인하였다. T세포를 활용한 참당귀 추출물의 면역조절 효능 평가를 위하여 IL-2, IL-4 및 IFN-𝛾 mRNA 발현 변화에 대한 영향을 측정하였다. 실험결과, 참당귀 추출물은 IL-2, IL-4 및 IFN-𝛾 세포 활성물질의 생성 조절을 통하여 면역조절 효능이 있음을 확인하였다. 본 연구결과를 통해 규명된 결과는 참당귀 추출물의 체력증진 및 면역조절을 위한 건강 기능성 제품개발에 활용 가능성을 제시하였다.

• Biomolecules & Therapeutics
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• 제27권3호
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• pp.290-301
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• 2019

Paeonol has neuroprotective function, which could be useful for improving central nervous system disorder. The purpose of this study was to characterize the functional mechanism involved in brain transport of paeonol through blood-brain barrier (BBB). Brain transport of paeonol was characterized by internal carotid artery perfusion (ICAP), carotid artery single injection technique (brain uptake index, BUI) and intravenous (IV) injection technique in vivo. The transport mechanism of paeonol was examined using conditionally immortalized rat brain capillary endothelial cell line (TR-BBB) as an in vitro model of BBB. Brain volume of distribution (VD) of [$^3H$]paeonol in rat brain was about 6-fold higher than that of [$^{14}C$]sucrose, the vascular space marker of BBB. The uptake of [$^3H$]paeonol was concentration-dependent. Brain volume of distribution of paeonol and BUI as in vivo and inhibition of analog as in vitro studies presented significant reduction effect in the presence of unlabeled lipophilic compounds such as paeonol, imperatorin, diphenhydramine, pyrilamine, tramadol and ALC during the uptake of [$^3H$]paeonol. In addition, the uptake significantly decreased and increased at the acidic and alkaline pH in both extracellular and intracellular study, respectively. In the presence of metabolic inhibitor, the uptake reduced significantly but not affected by sodium free or membrane potential disruption. Similarly, paeonol uptake was not affected on OCTN2 or rPMAT siRNA transfection BBB cells. Interestingly. Paeonol is actively transported from the blood to brain across the BBB by a carrier mediated transporter system.

• 한국축산식품학회지
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• 제30권1호
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• pp.1-12
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• 2010

The immune system is generally divided into the innate and the adopted immune systems, both protecting the body from pathogens. Recently, allergies, a disease associated with an imbalanced immune system, have increased rapidly in developed countries. Prevailing symptoms of allergic diseases are eczema, allergic rhinitis, asthma, inflammatory bowel disease, and food allergy. Probiotic bacteria, mainly consisting of lactic acid bacteria, are used in the prevention and treatment of allergic diseases. The function of them is to stimulate the intestinal immune cells and form a complex signal network to activate other immune cells. Beneficial health effects of probiotics are based on the hygiene hypothesis, which suggests that sanitary environment is important for health, but limited exposure to environmental factors increases allergic diseases. An immunoregulatory effect of probiotic bacteria is demonstrated by controlled trial, animal model, in vitro, in vivo and ex vivo designs. However, the immunoregulatory effect of probiotic bacteria is controversial because it depends on probiotic strains, a dose and a type of diseases. In this review, we discussed clinical evidences on immunoregulatory effects of probiotic bacteria.