• 제목/요약/키워드: molecular functions

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노화관련 질환에 대한 후성유전의 역할 (The Roles of Epigenetic Reprogramming in Age-related Diseases)

  • 황선화;김경민;김혜경;박민희
    • 생명과학회지
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    • 제33권9호
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    • pp.736-745
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    • 2023
  • 노화란 세포 및 생리 기능이 점진적으로 손상되는 복잡한 과정이다. 알츠하이머, 동맥경화 및 갱년기와 같은 노화와 관련된 질병은 노화가 진행이 되면서 발생된다. 노화와 관련된 질환은 다양한 원인에 의해 발생된다. 그 중 유전적인 변화 없이 유전자 발현을 조절하는 후성유전의 변화는 노화, 그리고 노화와 관련된 질환의 발생에 중요한 조절자로 알려져있다. 이 리뷰에서는 후성유전의 변화가 노화 및 노화와 관련된 질병의 발전과 진행에 어떠한 역할을 하는지에 대해 서술하였다. 노화 중에 일어나는 유전적 변화의 분자적 기전과 이러한 변화가 노화와 관련된 질병에 미치는 영향, 특히 노화와 관련된 질환과 관련된 유전자 발현 양식을 조절하는 RNA 메틸화, DNA 메틸화 및 miRNA에 대해 중점적으로 초점을 맞추었다.

The Bcl-2/Bcl-xL Inhibitor ABT-263 Attenuates Retinal Degeneration by Selectively Inducing Apoptosis in Senescent Retinal Pigment Epithelial Cells

  • Wonseon Ryu;Chul-Woo Park;Junghoon Kim;Hyungwoo Lee;Hyewon Chung
    • Molecules and Cells
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    • 제46권7호
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    • pp.420-429
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    • 2023
  • Age-related macular degeneration (AMD) is one of the leading causes of blindness in elderly individuals. However, the currently used intravitreal injections of anti-vascular endothelial growth factor are invasive, and repetitive injections are also accompanied by a risk of intraocular infection. The pathogenic mechanism of AMD is still not completely understood, but a multifactorial mechanism that combines genetic predisposition and environmental factors, including cellular senescence, has been suggested. Cellular senescence refers to the accumulation of cells that stop dividing due to the presence of free radicals and DNA damage. Characteristics of senescent cells include nuclear hypertrophy, increased levels of cell cycle inhibitors such as p16 and p21, and resistance to apoptosis. Senolytic drugs remove senescent cells by targeting the main characteristics of these cells. One of the senolytic drugs, ABT-263, which inhibits the antiapoptotic functions of Bcl-2 and Bcl-xL, may be a new treatment for AMD patients because it targets senescent retinal pigment epithelium (RPE) cells. We proved that it selectively kills doxorubicin (Dox)-induced senescent ARPE-19 cells by activating apoptosis. By removing senescent cells, the expression of inflammatory cytokines was reduced, and the proliferation of the remaining cells was increased. When ABT-263 was orally administered to the mouse model of senescent RPE cells induced by Dox, we confirmed that senescent RPE cells were selectively removed and retinal degeneration was alleviated. Therefore, we suggest that ABT-263, which removes senescent RPE cells through its senolytic effect, has the potential to be the first orally administered senolytic drug for the treatment of AMD.

Differential Proteomic Analysis of Chinese fir Clone Leaf Response to Salicylic Acid

  • Yang, Mei;Lin, Sizu;Cao, Guangqiu
    • Journal of Forest and Environmental Science
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    • 제26권2호
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    • pp.83-94
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    • 2010
  • Chinese fir (Latin name: Cunninghaimia lanceolata) is one of the major commercial coniferous trees. Most of Chinese fir forests are managed in successive rotation sites, which lead productivity to decline. Autotoxicity is the important reason for soil degradation of Chinese fir plantation, especially, phenolic acids are considered as the major allelopathic toxins which induce autotoxicity in Chinese fir rotation stands. We performed here proteomic approach to investigate the response of proteins in Chinese fir leaves to salicylic acid. The tube plantlets of Chinese fir clone were treated with 120 mg/L salicylic acid for 1, 3 and 5th day. 2-DE, coupled with MALDI-TOF-TOF/MS, was used to separate and identify the responsive proteins. We found 12, 7, and 12 candidate protein spots that were up- or down-regulated by at least 2.5 fold after 1, 3, and 5th day of the stress, respectively. Of these protein spots, 16 spots were identified successfully. According to the putative physiological functions, these proteins were categorized into five classes (1) the proteins involved in protein stability and folding, including 26S proteome, Grp78, Hsp70, Hsp90 and PPIase; (2) the protein involved in photosynthesis and respiration, including OEC 33 kDa subunit, GAPDH; (3) the protein related to cell endurance to acid, F-ATPase; (4) the protein related to cytoskeleton, tubulin; (5) the protein related to protein translation: prolyl-tRNA synthetase. These results give new insights into autotoxic substance stress response in Chinese fir leaves and provide preliminary footprints for further studies on the molecular signal mechanisms induced by the stress.

Profiling of differentially expressed proteins between fresh and frozen-thawed Duroc boar semen using ProteinChip CM10

  • Yong-Min Kim;Sung-Woo Park;Mi-Jin Lee;Da-Yeon Jeon;Su-Jin Sa;Yong-Dae Jeong;Ha-Seung Seong;Jung-Woo Choi;Shinichi, Hochi;Eun-Seok Cho;Hak-Jae Chung
    • Journal of Animal Science and Technology
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    • 제65권2호
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    • pp.401-411
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    • 2023
  • Many studies have been conducted to improve technology for semen cryopreservation in pigs. However, computer-assisted analysis of sperm motility and morphology is insufficient to predict the molecular function of frozen-thawed semen. More accurate expression patterns of boar sperm proteins may be derived using the isobaric tags for relative and absolute quantification (iTRAQ) technique. In this study, the iTRAQ-labeling system was coupled with liquid chromatography tandem-mass spectrometry (LC-MS/MS) analysis to identify differentially expressed CM10-fractionated proteins between fresh and frozen-thawed boar semen. A total of 76 protein types were identified to be differentially expressed, among which 9 and 67 proteins showed higher and lower expression in frozen-thawed than in fresh sperm samples, respectively. The classified functions of these proteins included oxidative phosphorylation, mitochondrial inner membrane and matrix, and pyruvate metabolic processes, which are involved in adenosine triphosphate (ATP) synthesis; and sperm flagellum and motile cilium, which are involved in sperm tail structure. These results suggest a possible network of biomarkers associated with survival after the cryopreservation of Duroc boar semen.

Reduction of fetuin-A levels contributes to impairment of Purkinje cells in cerebella of patients with Parkinson's disease

  • Sunmi Yoon;Napissara Boonpraman;Chae Young Kim;Jong-Seok Moon;Sun Shin Yi
    • BMB Reports
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    • 제56권5호
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    • pp.308-313
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    • 2023
  • Phenotypic features such as ataxia and loss of motor function, which are characteristics of Parkinson's disease (PD), are expected to be very closely related to cerebellum function. However, few studies have reported the function of the cerebellum. Since the cerebellum, like the cerebrum, is known to undergo functional and morphological changes due to neuroinflammatory processes, elucidating key functional factors that regulate neuroinflammation in the cerebellum can be a beneficial therapeutic approach. Therefore, we employed PD patients and MPTP-induced PD mouse model to find cytokines involved in cerebellar neuroinflammation in PD and to examine changes in cell function by regulating related genes. Along with the establishment of a PD mouse model, abnormal shapes such as arrangement and number of Purkinje cells in the cerebellum were confirmed based on histological finding, consistent with those of cerebellums of PD patients. As a result of proteome profiling for neuroinflammation using PD mouse cerebellar tissues, fetuin-A, a type of cytokine, was found to be significantly reduced in Purkinje cells. To further elucidate the function of fetuin-A, neurons isolated from cerebellums of embryos (E18) were treated with fetuin-A siRNA. We uncovered that not only the population of neuronal cells, but also their morphological appearances were significantly different. In this study, we found a functional gene called fetuin-A in the PD model's cerebellum, which was closely related to the role of cerebellar Purkinje cells of mouse and human PD. In conclusion, morphological abnormalities of Purkinje cells in PD mice and patients have a close relationship with a decrease of fetuin-A, suggesting that diagnosis and treatment of cerebellar functions of PD patients might be possible through regulation of fetuin-A.

Ubiquitin E3 ligases in cancer: somatic mutation and amplification

  • Eun-Hye Jo;Mi-Yeon Kim;Hyung-Ju Lee;Hee-Sae Park
    • BMB Reports
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    • 제56권5호
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    • pp.265-274
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    • 2023
  • Defects in DNA double-strand break (DSB) repair signaling permit cancer cells to accumulate genomic alterations that confer their aggressive phenotype. Nevertheless, tumors depend on residual DNA repair abilities to survive the DNA damage induced by genotoxic stress. This is why only isolated DNA repair signaling is inactivated in cancer cells. DNA DSB repair signaling contributes to general mechanism for various types of lesions in diverse cell cycle phases. DNA DSB repair genes are frequently mutated and amplified in cancer; however, limited data exist regarding the overall genomic prospect and functional result of these modifications. We list the DNA repair genes and related E3 ligases. Mutation and expression frequencies of these genes were analyzed in COSMIC and TCGA. The 11 genes with a high frequency of mutation differed between cancers, and mutations in many DNA DSB repair E3 ligase genes were related to a higher total mutation burden. DNA DSB repair E3 ligase genes are involved in tumor suppressive or oncogenic functions, such as RNF168 and FBXW7, by assisting the functionality of these genomic alterations. DNA damage response-related E3 ligases, such as RNF168, FBXW7, and HERC2, were generated with more than 10% mutation in several cancer cells. This study provides a broad list of candidate genes as potential biomarkers for genomic instability and novel therapeutic targets in cancer. As a DSB related proteins considerably appear the possibilities for targeting DNA repair defective tumors or hyperactive DNA repair tumors. Based on recent research, we describe the relationship between unstable DSB repairs and DSB-related E3 ligases.

A bioinformatics approach to characterize a hypothetical protein Q6S8D9_SARS of SARS-CoV

  • Md Foyzur Rahman;Rubait Hasan;Mohammad Shahangir Biswas;Jamiatul Husna Shathi;Md Faruk Hossain;Aoulia Yeasmin;Mohammad Zakerin Abedin;Md Tofazzal Hossain
    • Genomics & Informatics
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    • 제21권1호
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    • pp.3.1-3.10
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    • 2023
  • Characterization as well as prediction of the secondary and tertiary structure of hypothetical proteins from their amino acid sequences uploaded in databases by in silico approach are the critical issues in computational biology. Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), which is responsible for pneumonia alike diseases, possesses a wide range of proteins of which many are still uncharacterized. The current study was conducted to reveal the physicochemical characteristics and structures of an uncharacterized protein Q6S8D9_SARS of SARS-CoV. Following the common flowchart of characterizing a hypothetical protein, several sophisticated computerized tools e.g., ExPASy Protparam, CD Search, SOPMA, PSIPRED, HHpred, etc. were employed to discover the functions and structures of Q6S8D9_SARS. After delineating the secondary and tertiary structures of the protein, some quality evaluating tools e.g., PROCHECK, ProSA-web etc. were performed to assess the structures and later the active site was identified also by CASTp v.3.0. The protein contains more negatively charged residues than positively charged residues and a high aliphatic index value which make the protein more stable. The 2D and 3D structures modeled by several bioinformatics tools ensured that the proteins had domain in it which indicated it was functional protein having the ability to trouble host antiviral inflammatory cytokine and interferon production pathways. Moreover, active site was found in the protein where ligand could bind. The study was aimed to unveil the features and structures of an uncharacterized protein of SARS-CoV which can be a therapeutic target for development of vaccines against the virus. Further research are needed to accomplish the task.

Golgi Stress Response: New Insights into the Pathogenesis and Therapeutic Targets of Human Diseases

  • Won Kyu Kim;Wooseon Choi;Barsha Deshar;Shinwon Kang;Jiyoon Kim
    • Molecules and Cells
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    • 제46권4호
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    • pp.191-199
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    • 2023
  • The Golgi apparatus modifies and transports secretory and membrane proteins. In some instances, the production of secretory and membrane proteins exceeds the capacity of the Golgi apparatus, including vesicle trafficking and the post-translational modification of macromolecules. These proteins are not modified or delivered appropriately due to the insufficiency in the Golgi function. These conditions disturb Golgi homeostasis and induce a cellular condition known as Golgi stress, causing cells to activate the 'Golgi stress response,' which is a homeostatic process to increase the capacity of the Golgi based on cellular requirements. Since the Golgi functions are diverse, several response pathways involving TFE3, HSP47, CREB3, proteoglycan, mucin, MAPK/ETS, and PERK regulate the capacity of each Golgi function separately. Understanding the Golgi stress response is crucial for revealing the mechanisms underlying Golgi dynamics and its effect on human health because many signaling molecules are related to diseases, ranging from viral infections to fatal neurodegenerative diseases. Therefore, it is valuable to summarize and investigate the mechanisms underlying Golgi stress response in disease pathogenesis, as they may contribute to developing novel therapeutic strategies. In this review, we investigate the perturbations and stress signaling of the Golgi, as well as the therapeutic potentials of new strategies for treating Golgi stress-associated diseases.

Transcriptome Profiling of Differentially Expressed Genes in Cowpea (Vigna unguiculata L.) Under Salt Stress

  • Byeong Hee Kang;Woon Ji Kim;Sreepama Chowdhury;Chang Yeok Moon;Sehee Kang;Bo-Keun Ha
    • 한국작물학회:학술대회논문집
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    • 한국작물학회 2022년도 추계학술대회
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    • pp.261-261
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    • 2022
  • Cowpea [Vigna unguiculata (L.) Walp] is one of the most important grain legumes that enhance soil fertility and is well-adapted to various abiotic stress. Also, it is cultivated worldwide as a tropical annual crop, and the semi-arid regions are known as the main cowpea-produced regions. However, accumulation of soil salinity induced by low rainfall in these regions is reducing crop yields and quality. In general, plants exposed to soil salinity cause an accumulation of high ion chloride, which leads to the degradation of root and leaf proteins. In this study, we identified candidate genes associated with salinity tolerance through an analysis of differentially expressed genes (DEGs) in four cowpea germplasms with contrasting salinity tolerance. A total of 553,776,035 short reads were obtained using the Illumina Novaseq 6000 platform for RNA-Seq, which were subsequently aligned to the reference genome of cowpea Vunguiculata v1.2. A total of9,806 DEGs were identified between NaCl treatment and control of four cowpea germplasms. Among these DEGs, functions related to salt stress such as calcium transporter and cytochrome-450 family were associated with salt stress. In GO analysis and KEGG analysis, these DEGs were enriched in terms such as the "phosphorylation", ''extracellular region", and "ion binding". These RNA-seq results will improve the understanding of the salt tolerance of cowpea and can be used as useful basic data for molecular breeding technology in the future.

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미세 유체 기반의 형광 다중 암 진단 센서 플랫폼 설계 (Design of Fluorescence Multi-cancer Diagnostic Sensor Platform based on Microfluidics)

  • 이병권;칼리크 아민;정명영
    • 마이크로전자및패키징학회지
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    • 제29권4호
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    • pp.55-61
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    • 2022
  • 다중 암의 동시 진단 기술에 대한 관심이 전 세계적으로 증가하는 추세이며, 진단 난이도를 낮추기 위해 혈액과 같은 미량의 바이오 유체를 이용하여 질병을 진단하는 미세 유체 소자 기반의 액체 생검 기술이 연구되고 있다. 바이오 유체를 이용하여 형광 영상 등을 통해 분석물질의 농도를 측정하는 광학적 바이오 센싱에 있어 민감도를 향상시키기 위한 기술개발이 필요하다. 본 논문에서는 모세관력에 의한 자가구동 기반의 마이크로 채널의 기하학적 구조와 미세 유체 현상만으로 수동적 자기 혈장 분리 기술과 유체 혼합을 통한 분자 인식 활성화 기능을 구현하는 형광 다중 암 진단 센서 플랫폼 구조를 제안하고 설계하였다. 설계된 센서의 혈장 분리부의 성능에 영향을 미치는 파라미터를 확인하기 위해 채널의 수력학적 직경과 종횡비, 유체의 점도를 변수로 설정하여 딘 와류 형성 여부를 시뮬레이션을 통해 확인하였고 최적의 센서 플랫폼 구조를 제시하였다.