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Comprehensive identification of VX-adducted plasma proteins using high-resolution mass spectrometry
Hazara Begum Mohammad,Min-Sik Kim,Ji Hwan Park,Jun Hyung Lee,Minh Hung Vu,Jin-Young Lee,Woo-Hyeon Jeong 대한화학회 2022 Bulletin of the Korean Chemical Society Vol.43 No.10
VX is one of the chemical warfare agents that attack victims’nervous systemsand ultimately lead to their death. Upon VX exposure, circulating proteins in thebloodstream can be modified with VX that may produce diagnostic VX adducts.Thus, these adducts would be key evidence for the forensic investigation againstchemical warfare or terrorism. In this study, we discovered a list of potentialblood protein biomarkers for VX exposure. To do so, we employed high-resolution mass spectrometry-based proteomics and identified 18 VX-adductedproteins with 32 adduct sites from VX-treated human plasma samples. Further-more, we examined these targets using a data-independent acquisition methodand obtained eight practically detectable biomarkers. Our results may serve as avaluable resource for verifying nerve agent exposure under chemical attack.
Identification of organophosphate modifications by high‐resolution mass spectrometry
Lee Jun Hyung,Jang Wooyoung Eric,Park Ji Hwan,Mohammad Hazara Begum,Lee Jin‐Young,Jeong Woo‐Hyeon,Kim Min‐Sik 대한화학회 2022 Bulletin of the Korean Chemical Society Vol.43 No.3
Organophosphate (OP) compounds exhibit neurotoxicity by binding to serine residues of acetylcholinesterase (AChE) in the cholinergic nervous system and subsequently lead to the accumulation of acetylcholine in neuromuscular junctions of synapses. AChE capable of hydrolyzing choline esters is known to be inhibited in patients with nerve agents poisoning. Since OP is known to be transported by covalent bonding to human serum albumin (HSA), OP-HSA adducts are considered potential diagnostic markers for OP exposures. In this study, HSA modification sites by OP or OP-like compounds such as V-type (VX) and Novichok-type (A234), insecticide (DFP), and serine protease inhibitor (PMSF) were studied using liquid chromatography-high-resolution tandem mass spectrometry. As a result, we have discovered a novel OP-HSA modification site, Y341.
Park Gaeun,Jang Wooyoung Eric,Kim Seoyeon,Gonzales Edson Luck,Ji Jungeun,Choi Seunghwan,Kim Yujin,Park Ji Hwan,Mohammad Hazara Begum,Bang Geul,Kang Minkyung,Kim Soobin,Jeon Se Jin,Kim Jin Young,Kim Kw 생화학분자생물학회 2023 Experimental and molecular medicine Vol.55 No.-
Autism spectrum disorder (ASD) is a neurodevelopmental disorder associated with impaired social behavior and communication, repetitive behaviors, and restricted interests. In addition to genetic factors, environmental factors such as prenatal drug exposure contribute to the development of ASD. However, how those prenatal factors induce behavioral deficits in the adult stage is not clear. To elucidate ASD pathogenesis at the molecular level, we performed a high-resolution mass spectrometry-based quantitative proteomic analysis on the prefrontal cortex (PFC) of mice exposed to valproic acid (VPA) in utero, a widely used animal model of ASD. Differentially expressed proteins (DEPs) in VPA-exposed mice showed significant overlap with ASD risk genes, including differentially expressed genes from the postmortem cortex of ASD patients. Functional annotations of the DEPs revealed significant enrichment in the Wnt/β-catenin signaling pathway, which is dysregulated by the upregulation of Rnf146 in VPA-exposed mice. Consistently, overexpressing Rnf146 in the PFC impaired social behaviors and altered the Wnt signaling pathway in adult mice. Furthermore, Rnf146-overexpressing PFC neurons showed increased excitatory synaptic transmission, which may underlie impaired social behavior. These results demonstrate that Rnf146 is critical for social behavior and that dysregulation of Rnf146 underlies social deficits in VPA-exposed mice.