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Article ; Online: Generating Detailed Spectral Libraries for Canine Proteomes Obtained from Serum and Urine

Hee-Sung Ahn / Jeonghun Yeom / Jiyoung Yu / Yumi Oh / JeongYeon Hong / Minjung Kim / Kyunggon Kim

Scientific Data, Vol 10, Iss 1, Pp 1-

2023 Volume 7

Abstract: Abstract Domestic dogs (Canis lupus familiaris) are popular companion animals. Increase in medical expenses associated with them and demand for extending their lifespan in a healthy manner has created the need to develop new diagnostic technology. ... ...

Abstract	Abstract Domestic dogs (Canis lupus familiaris) are popular companion animals. Increase in medical expenses associated with them and demand for extending their lifespan in a healthy manner has created the need to develop new diagnostic technology. Companion dogs also serve as important animal models for non-clinical research as they can provide various biological phenotypes. Proteomics have been increasingly used on dogs and humans to identify novel biomarkers of various diseases. Despite the growing applications of proteomics in liquid biopsy in veterinary medicine, no publicly available spectral assay libraries have been created for the proteome of canine serum and urine. In this study, we generated spectral assay libraries for the two-representative liquid-biopsy samples using mid-pH fractionation that allows in-depth understanding of proteome coverage. The resultant canine serum and urine spectral assay libraries include 1,132 and 4,749 protein groups and 5,483 and 25,228 peptides, respectively. We built these complimentary accessible resources for proteomic biomarker discovery studies through ProteomeXchange with the identifier PXD034770.
Keywords	Science ; Q
Subject code	630
Language	English
Publishing date	2023-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Understanding the molecular mechanism of pathogenic variants of BIR2 domain in XIAP-deficient inflammatory bowel disease

Juhwan Lee / Kyoung Mi Sim / Mooseok Kang / Hyun Ju Oh / Ho Jung Choi / Yeong Eun Kim / Chan-Gi Pack / Kyunggon Kim / Kyung Mo Kim / Seak Hee Oh / Inki Kim / Iksoo Chang

Scientific Reports, Vol 14, Iss 1, Pp 1-

2024 Volume 14

Abstract: Abstract X-linked inhibitor of apoptosis protein (XIAP) deficiency causes refractory inflammatory bowel disease. The XIAP protein plays a pivotal role in the pro-inflammatory response through the nucleotide-binding oligomerization domain-containing ... ...

Abstract	Abstract X-linked inhibitor of apoptosis protein (XIAP) deficiency causes refractory inflammatory bowel disease. The XIAP protein plays a pivotal role in the pro-inflammatory response through the nucleotide-binding oligomerization domain-containing signaling pathway that is important in mucosal homeostasis. We analyzed the molecular mechanism of non-synonymous pathogenic variants (PVs) of XIAP BIR2 domain. We generated N-terminally green fluorescent protein-tagged XIAP constructs of representative non-synonymous PVs. Co-immunoprecipitation and fluorescence cross-correlation spectroscopy showed that wild-type XIAP and RIP2 preferentially interacted in live cells, whereas all non-synonymous PV XIAPs failed to interact properly with RIP2. Structural analysis showed that various structural changes by mutations, such as hydrophobic core collapse, Zn-finger loss, and spatial rearrangement, destabilized the two loop structures (174–182 and 205–215) that critically interact with RIP2. Subsequently, it caused a failure of RIP2 ubiquitination and loss of protein deficiency by the auto-ubiquitination of all XIAP mutants. These findings could enhance our understanding of the role of XIAP mutations in XIAP-deficient inflammatory bowel disease and may benefit future therapeutic strategies.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Protein Translocation Acquires Substrate Selectivity Through ER Stress-Induced Reassembly of Translocon Auxiliary Components

Sohee Lee / Yejin Shin / Kyunggon Kim / Youngsup Song / Yongsub Kim / Sang-Wook Kang

Cells, Vol 9, Iss 2, p

2020 Volume 518

Abstract: Protein import across the endoplasmic reticulum membrane is physiologically regulated in a substrate-selective manner to ensure the protection of stressed ER from the overload of misfolded proteins. However, it is poorly understood how different types of ...

Abstract	Protein import across the endoplasmic reticulum membrane is physiologically regulated in a substrate-selective manner to ensure the protection of stressed ER from the overload of misfolded proteins. However, it is poorly understood how different types of substrates are accurately distinguished and disqualified during translocational regulation. In this study, we found poorly assembled translocon-associated protein (TRAP) complexes in stressed ER. Immunoaffinity purification identified calnexin in the TRAP complex in which poor assembly inhibited membrane insertion of the prion protein (PrP) in a transmembrane sequence-selective manner, through translocational regulation. This reaction was induced selectively by redox perturbation, rather than calcium depletion, in the ER. The liberation of ERp57 from calnexin appeared to be the reason for the redox sensitivity. Stress-independent disruption of the TRAP complex prevented a pathogenic transmembrane form of PrP (ctmPrP) from accumulating in the ER. This study uncovered a previously unappreciated role for calnexin in assisting the redox-sensitive function of the TRAP complex and provided insights into the ER stress-induced reassembly of translocon auxiliary components as a key mechanism by which protein translocation acquires substrate selectivity.
Keywords	protein translocation ; protein quality control ; prion protein ; er stress ; redox homeostasis ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2020-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Systemic antibiotics cause deterioration of emphysema associated with exaggerated inflammation and autophagy

Na Hyun Kim / Bo-Yun Choi / Eun Sil Kim / Su Jung Kim / Jeong Yeon Hong / Sun-Hee Heo / Jin-Yong Jeong / Kyunggon Kim / Hyun Ju Yoo / Woo Jun Sul / Sei Won Lee

Experimental and Molecular Medicine, Vol 55, Iss 10, Pp 2260-

2023 Volume 2268

Abstract: Abstract The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it ... ...

Abstract	Abstract The interaction between the microbial environment and the host is important for immune homeostasis. Recent research suggests that microbiota dysbiosis can be involved in respiratory diseases. Emphysema is a chronic inflammatory disease, but it is unclear whether dysbiosis caused by antibiotics can affect disease progression. Here, we tried to elucidate the effect of systemic antibiotics on smoking-exposed emphysema models. In this study, the antibiotic mixture caused more alveolar destruction and airspace expansion in the smoking group than in the smoking only or control groups. This emphysema aggravation as a result of antibiotic exposure was associated with increased levels of inflammatory cells, IL-6, IFNγ and protein concentrations in bronchoalveolar lavage fluid. Proteomics analysis indicated that autophagy could be involved in antibiotic-associated emphysema aggravation, and increased protein levels of LC3B, atg3, and atg7 were identified by Western blotting. In microbiome and metabolome analyses, the composition of the gut microbiota was different with smoking and antibiotic exposure, and the levels of short-chain fatty acids (SCFAs), including acetate and propionate, were reduced by antibiotic exposure. SCFA administration restored emphysema development with reduced inflammatory cells, IL-6, and IFNγ and decreased LC3B, atg3, and atg7 levels. In conclusion, antibiotics can aggravate emphysema, and inflammation and autophagy may be associated with this aggravation. This study provides important insight into the systemic impact of microbial dysbiosis and the therapeutic potential of utilizing the gut microbiota in emphysema.
Keywords	Medicine ; R ; Biochemistry ; QD415-436
Subject code	610
Language	English
Publishing date	2023-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Lack of association between serum myonectin levels and sarcopenia in older Asian adults

Sunghwan Ji / So Jeong Park / Jin Young Lee / Ji Yeon Baek / Hee-Won Jung / Kyunggon Kim / Hyun Ju Yoo / Il-Young Jang / Beom-Jun Kim

Experimental Gerontology, Vol 178, Iss , Pp 112229- (2023)

2023

Abstract: Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its ... ...

Abstract	Myonectin is a muscle-secreted factor that helps maintain homeostasis in the body by regulating several functions, including lipid metabolism. Previous studies suggested that myonectin may play a role in muscle health in an autocrine manner, but its impact on human skeletal muscle is still unclear. We aimed to investigate the relationship of serum myonectin levels with sarcopenia and related muscle parameters. We conducted a cross-sectional study of 142 older adults whose muscle mass, grip strength, gait speed, chair stands, and short physical performance battery (SPPB) were evaluated in the geriatric clinic of a tertiary medical center. Sarcopenia was defined based on Asian-specific cutoff values, and circulating myonectin levels were measured using an enzyme immunoassay. Before and after adjusting for age, sex, and body mass index, the serum myonectin level was not significantly different when the patients were stratified by status of sarcopenia, muscle mass, muscle strength, and physical performance. Furthermore, whether given as a continuous variable or divided into quartile groups, the serum myonectin level had no association with the skeletal muscle mass, grip strength, gait speed, chair stand test, or SPPB score. Our findings did not confirm the potential role of myonectin in muscle metabolism observed in experimental research. Thus, serum myonectin levels cannot predict the risk of sarcopenia in older Asian adults.
Keywords	Sarcopenia ; Myonectin ; Myokine ; Biomarker ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	796
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Proteomic analysis predicts anti-angiogenic resistance in recurred glioblastoma

Hanwool Jeon / Joonho Byun / Hayeong Kang / Kyunggon Kim / Eunyeup Lee / Jeong Hoon Kim / Chang Ki Hong / Sang Woo Song / Young-Hoon Kim / Sangjoon Chong / Jae Hyun Kim / Soo Jeong Nam / Ji Eun Park / Seungjoo Lee

Journal of Translational Medicine, Vol 21, Iss 1, Pp 1-

2023 Volume 19

Abstract: Abstract Background Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median ... ...

Abstract	Abstract Background Recurrence is common in glioblastoma multiforme (GBM) because of the infiltrative, residual cells in the tumor margin. Standard therapy for GBM consists of surgical resection followed by chemotherapy and radiotherapy, but the median survival of GBM patients remains poor (~ 1.5 years). For recurrent GBM, anti-angiogenic treatment is one of the common treatment approaches. However, current anti-angiogenic treatment modalities are not satisfactory because of the resistance to anti-angiogenic agents in some patients. Therefore, we sought to identify novel prognostic biomarkers that can predict the therapeutic response to anti-angiogenic agents in patients with recurrent glioblastoma. Methods We selected patients with recurrent GBM who were treated with anti-angiogenic agents and classified them into responders and non-responders to anti-angiogenic therapy. Then, we performed proteomic analysis using liquid-chromatography mass spectrometry (LC–MS) with formalin-fixed paraffin-embedded (FFPE) tissues obtained from surgical specimens. We conducted a gene-ontology (GO) analysis based on protein abundance in the responder and non-responder groups. Based on the LC–MS and GO analysis results, we identified potential predictive biomarkers for anti-angiogenic therapy and validated them in recurrent glioblastoma patients. Results In the mass spectrometry-based approach, 4957 unique proteins were quantified with high confidence across clinical parameters. Unsupervised clustering analysis highlighted distinct proteomic patterns (n = 269 proteins) between responders and non-responders. The GO term enrichment analysis revealed a cluster of genes related to immune cell-related pathways (e.g., TMEM173, FADD, CD99) in the responder group, whereas the non-responder group had a high expression of genes related to nuclear replisome (POLD) and damaged DNA binding (ERCC2). Immunohistochemistry of these biomarkers showed that the expression levels of TMEM173 and FADD were significantly associated with the overall ...
Keywords	Anti-angiogenic resistance ; Prediction biomarker ; Proteomics ; Medicine ; R
Subject code	610
Language	English
Publishing date	2023-02-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparative Analysis of Proteomes and Phosphoproteomes in Patients with Prostate Cancer Using Different Surgical Conditions

Hee-Sung Ahn / Jeonghun Yeom / Hwangkyo Jeong / Won Young Park / Ja Yoon Ku / Byeong Jin Kang / Kyung Hwan Kim / Chan Ho Lee / Sangheon Song / Sun Sik Bae / Kyunggon Kim / Hong Koo Ha

The World Journal of Men's Health, Vol 40, Iss 4, Pp 608-

2022 Volume 617

Abstract: Purpose: To establish the standard of procedure in preparing benign and cancerous prostate tissues and evaluate the quality of proteomics and phosphoproteomics during transurethral resection of the prostate (TUR-P) with different surgical conditions. ... ...

Abstract	Purpose: To establish the standard of procedure in preparing benign and cancerous prostate tissues and evaluate the quality of proteomics and phosphoproteomics during transurethral resection of the prostate (TUR-P) with different surgical conditions. Materials and Methods: TUR-P tissue samples from three patients, two diagnosed with prostate cancer and one with benign prostatic hyperplasia, were each analyzed under three different conditions, based on differences in energy values, tissue locations, and surgical techniques. Global- and phosphorylated proteomic profiles of prostate tissues were analyzed by liquid chromatography-tandem mass spectrometry. Results: A total of 6,019 global proteins and 4,280 phosphorylated peptides were identified in the nine tissues. The quantitative distributions of proteins and phosphorylation in tissues from the same patient were not affected by changes in the surgical conditions, but indirect relative comparisons differed among patients. Phosphorylation levels, especially of proteins involved in the androgen receptor pathway, important in prostate cancer, were preserved in each patient. Conclusions: Proteomic profiles of prostate tissue collected by TUR-P were not significantly affected by energy levels, tissue location, or surgical technique. In addition, since protein denaturation of samples through TUR-P is rarely confirmed in this study, we think that it will be an important guide for tissue samples in castration resistant prostate cancer patients, where it is difficult to obtain tissue. This result is the first report about proteomic and phosphoproteomic results with TUR-P samples in prostate cancer and will be theoretical basis in protein analysis research with prostate cancer tissues.
Keywords	mass spectrometry ; prostatic hyperplasia ; prostatic neoplasm ; proteme ; transurethral resection of prostate ; Medicine ; R ; Diseases of the genitourinary system. Urology ; RC870-923
Subject code	610
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	Korean Society for Sexual Medicine and Andrology
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Function of Drosophila USP14 in Endoplasmic Reticulum Stress and Retinal Degeneration in a Model for Autosomal Dominant Retinitis Pigmentosa

Jung-Eun Park / Thị Xuân Thùy Trần / Nayoung Park / Jeonghun Yeom / Kyunggon Kim / Min-Ji Kang

Biology, Vol 9, Iss 332, p

2020 Volume 332

Abstract: Endoplasmic reticulum (ER) stress and its adaptive cellular response, the unfolded protein response (UPR), are involved in various diseases including neurodegenerative diseases, metabolic diseases, and even cancers. Here, we analyzed the novel function ... ...

Abstract	Endoplasmic reticulum (ER) stress and its adaptive cellular response, the unfolded protein response (UPR), are involved in various diseases including neurodegenerative diseases, metabolic diseases, and even cancers. Here, we analyzed the novel function of ubiquitin-specific peptidase 14 (USP14) in ER stress. The overexpression of Drosophila USP14 protected the cells from ER stress without affecting the proteasomal activity. Null Hong Kong (NHK) and alpha-1-antitrypsin Z (ATZ) are ER-associated degradation substrates. The degradation of NHK, but not of ATZ, was delayed by USP14. USP14 restored the levels of rhodopsin-1 protein in a Drosophila model for autosomal dominant retinitis pigmentosa and suppressed the retinal degeneration in this model. In addition, we observed that proteasome complex is dynamically reorganized in response to ER stress in human 293T cells. These findings suggest that USP14 may be a therapeutic strategy in diseases associated with ER stress.
Keywords	USP14 ; ER stress ; retinal degeneration ; Drosophila ; Biology (General) ; QH301-705.5
Subject code	570
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Identification of a novel therapeutic target underlying atypical manifestation of Gaucher disease

Eun Na Kim / Hyo‐Sang Do / Hwangkyo Jeong / Taeho Kim / Sun Hee Heo / Yoo‐Mi Kim / Chong Kun Cheon / Yena Lee / Yunha Choi / In Hee Choi / Jeongmin Choi / Han‐Wook Yoo / Chong Jai Kim / Ari Zimran / Kyunggon Kim / Beom Hee Lee

Clinical and Translational Medicine, Vol 12, Iss 5, Pp n/a-n/a (2022)

2022

Keywords	Medicine (General) ; R5-920
Language	English
Publishing date	2022-05-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Long-Lasting Growth Hormone Regulated by the Ubiquitin-Proteasome System

Myung-Sun Kim / Kyunggon Kim / Su Kyung Oh / Gidae Lee / Jin-Ock Kim / Lan Li / Jung-Hyun Park / Kwang-Hyun Baek

International Journal of Molecular Sciences, Vol 22, Iss 6268, p

2021 Volume 6268

Abstract: To increase the half-life of growth hormones, we proposed its long-lasting regulation through the ubiquitin-proteasome system (UPS). We identified lysine residues (K67, K141, and K166) that are involved in the ubiquitination of human growth hormone (hGH) ...

Abstract	To increase the half-life of growth hormones, we proposed its long-lasting regulation through the ubiquitin-proteasome system (UPS). We identified lysine residues (K67, K141, and K166) that are involved in the ubiquitination of human growth hormone (hGH) using ubiquitination site prediction programs to validate the ubiquitination sites, and then substituted these lysine residues with arginine residues. We identified the most effective substituent (K141R) to prevent ubiquitination and named it AUT-hGH. hGH was expressed and purified in the form of hGH-His, and ubiquitination was first verified at sites containing K141 in the blood stream. Through the study, we propose that AUT-hGH with an increased half-life could be used as a long-lasting hGH in the blood stream.
Keywords	anti-ubiquitination technology ; half-life ; hGH ; ubiquitination ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	MDPI AG
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Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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