Inhibitory effect of tartrate against phosphate-induced DJ-1 aggregation

Kim, Min Soo,Lee, Sangmin,Yun, Sanguk,Suh, Pann-Ghill,Park, Jongmi,Cui, Minghua,Choi, Sun,Cha, Sun-Shin,Jin, Wook Elsevier 2018 INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES Vol.107 No.2

<P><B>Abstract</B></P> <P>The DJ-1 protein engages in diverse cellular and pathological processes, including tumorigenesis, apoptosis, sperm fertilization, and the progression of Parkinson’s disease (PD). The functional dimeric form of DJ-1 transforms into non-functional filamentous aggregates in an inorganic phosphate (P<SUB>i</SUB>)-dependent manner in vitro. Here, we demonstrated that P<SUB>i</SUB> and reactive oxygen species (ROS) induce DJ-1 aggregation in Neuro2A and SH-SY5Y cells. Remarkably, tartrate treatment significantly reduced P<SUB>i</SUB>- and ROS-induced DJ-1 aggregation and restored P<SUB>i</SUB>- and ROS-provoked cell death using quantitative data as mean±standard deviation, and statistics. Mechanistically, tartrate prevented DJ-1 aggregation via occupying the P<SUB>i</SUB>-binding site. These findings revealed an unexpected physiological role of tartrate in the maintenance of DJ-1 function, and thus, a potential use as an inhibitor of DJ-1 aggregation.</P>

Time-series transcriptomic analysis of the kelp grouper Epinephelus moara in response to low salinity stress

Quanxin Gao,Yanfeng Yue,Minghua Min,Shiming Peng,Zhaohong Shi,Jinbo Wang,Tao Zhang 한국통합생물학회 2018 Animal cells and systems Vol.22 No.4

The Kelp grouper Epinephelus moara is one of the most widely consumed and economically important marine fish in China. The species can tolerate a wide range of salinity, but genomic resources are not available, and the molecular mechanisms underlying adaptation to salinity at the transcriptomic level remain largely unclear. In this study, the transcriptomic responses of the liver of E. moara under low salinity were investigated using the Illumina digital gene expression system. After de novo assembly, 499,356 transcripts were generated and contributed 445,068 unigenes. A total of 14, 19, 33 and 3101 genes were differentially expressed following exposure to low salinity stress for 2, 6, 24 and 48 h, respectively. Only two genes were differentially expressed in all groups. Four genes related to metabolism and ambient salinity adaption were randomly selected to validate the differentially expressed genes (DEGs) by real-time PCR. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to analyse the functional significance of DEGs, including those responding to salinity through diverse biological processes, cellular components, molecular functions, and pathways associated with metabolic and osmotic responses. This work provides new insight into the response to salinity challenges in E. moara, and the findings expand our knowledge of the molecular basis of metabolic regulation mechanisms in this species. Additionally, the transcriptional data provide a valuable resource for future molecular and genetic studies on E. moara.

Nanoplastic Ingestion Enhances Toxicity of Persistent Organic Pollutants (POPs) in the Monogonont Rotifer <i>Brachionus koreanus</i> via Multixenobiotic Resistance (MXR) Disruption

Jeong, Chang-Bum,Kang, Hye-Min,Lee, Young Hwan,Kim, Min-Sub,Lee, Jin-Sol,Seo, Jung Soo,Wang, Minghua,Lee, Jae-Seong American Chemical Society 2018 Environmental science & technology Vol.52 No.19

<P>Among the various materials found inside microplastic pollution, nanosized microplastics are of particular concern due to difficulties in quantification and detection; moreover, they are predicted to be abundant in aquatic environments with stronger toxicity than microsized microplastics. Here, we demonstrated a stronger accumulation of nanosized microbeads in the marine rotifer <I>Brachionus koreanus</I> compared to microsized ones, which was associated with oxidative stress-induced damages on lipid membranes. In addition, multixenobiotic resistance conferred by <I>P</I>-glycoproteins and multidrug resistance proteins, as a first line of membrane defense, was inhibited by nanoplastic pre-exposure, leading to enhanced toxicity of 2,2′,4,4′-tetrabromodiphenyl ether and triclosan in <I>B. koreanus</I>. Our study provides a molecular mechanistic insight into the toxicity of nanosized microplastics toward aquatic invertebrates and further implies the significance of synergetic effects of microplastics with other environmental persistent organic pollutants.</P> [FIG OMISSION]</BR>

Adverse effects of methylmercury (MeHg) on life parameters, antioxidant systems, and MAPK signaling pathways in the copepod <i>Tigriopus japonicus</i>

Lee, Young Hwan,Kang, Hye-Min,Kim, Duck-Hyun,Wang, Minghua,Jeong, Chang-Bum,Lee, Jae-Seong Elsevier 2017 Aquatic toxicology Vol.184 No.-

<P><B>Abstract</B></P> <P>Methylmercury (MeHg) is a concerning environmental pollutant that bioaccumulates and biomagnifies in the aquatic food web. However, the effects of MeHg on marine zooplankton are poorly understood even though zooplankton are considered key mediators of the bioaccumulation and biomagnification of MeHg in high-trophic marine organisms. Here, the toxicity of MeHg in the benthic copepod <I>Tigriopus japonicus</I> was assessed, and its adverse effects on growth rate and reproduction were demonstrated. Antioxidant enzymatic activities were increased in the presence of MeHg, indicating that these enzymes play an important role in the defense response to MeHg, which is regulated by a complex mechanism. Subsequent activation of different patterns of mitogen-activated protein kinase (MAPK) pathways was demonstrated, providing a mechanistic approach to understand the signaling pathways involved in the effects of MeHg. Our results provide valuable information for understanding the toxicity of MeHg and the underlying defense mechanism in response to MeHg exposure in marine zooplankton.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The toxicity of MeHg in <I>Tigriopus japonicus</I> was assessed. </LI> <LI> Adverse effects on growth rate and reproduction were demonstrated upon MeHg. </LI> <LI> Antioxidant enzymatic activities were increased in the presence of MeHg. </LI> <LI> Subsequent activation of MAPK pathways was demonstrated in response to MeHg. </LI> </UL> </P>

Adverse effects of BDE-47 on life cycle parameters, antioxidant system, and activation of MAPK signaling pathway in the rotifer <i>Brachionus koreanus</i>

Park, Jun Chul,Han, Jeonghoon,Lee, Min-Chul,Kang, Hye-Min,Jeong, Chang-Bum,Hwang, Dae-Sik,Wang, Minghua,Lee, Jae-Seong Elsevier 2017 Aquatic toxicology Vol.186 No.-

<P><B>Abstract</B></P> <P>2,2′,4,4′-Tetrabromodiphenyl ether (BDE-47) is widely dispersed endocrine disrupting chemicals (EDCs) in the aquatic ecosystem. Due to its devastating effect on marine organisms and insufficient database on toxicology, we investigated the adverse effects of BDE-47 on life parameters and antioxidant defense system following the reactive oxygen species (ROS) production in the monogonont rotifer <I>Brachionus koreanus</I>. In <I>B. koreanus</I>, the reduction in life cycle, fecundity, and population growth were observed in response to BDE-47. 50μg/L BDE-47 significantly reduced (<I>P</I> <0.05) life expectancy and net reproductive rate. In response to 10–50μg/L BDE-47 exposure, the oxidative stress was elicited via the generation of ROS, while the antioxidant related enzymes (e.g. glutathione <I>S</I>-transferase [GST] and glutathione reductase [GR]) have demonstrated significant activity levels (<I>P</I> <0.05) to further alleviate the oxidative stress in a concentration dependent manner. Furthermore, transcript profiles of antioxidant function (<I>GST-A</I>, <I>-O</I>, and -<I>S1–S8</I>)-related genes have shown the significant increase over 24h in response to BDE-47 (0, 10, 25, and 50μg/L). As for MAPK signaling pathway analysis, up-regulation of their activities was observed at 25μg/L BDE-47 but their activities have reduced at adult NOEC concentration of 50μg/L. This study provides a better understanding of the effects of BDE-47 on life parameters, molecular defense system, and activation of MAPK signaling pathway against generated oxidants in the rotifer.</P> <P><B>Highlights</B></P> <P> <UL> <LI> 50μg/L BDE-47 significantly reduced (<I>P</I> <0.05) life expectancy and net reproductive rate. </LI> <LI> The oxidative stress was elicited via the generation of ROS after 10–50μg/L BDE-47 exposure. </LI> <LI> Antioxidant related enzymatic activities were significantly uprelated (<I>P</I> <0.05) due to oxidative stress. </LI> <LI> Transcript profiles of antioxidant function-related genes were significantly increased over 24h. </LI> <LI> Activation of MAPK signaling pathway was observed at 25μg/L BDE-47. </LI> </UL> </P>

Adverse effects of methylmercury (MeHg) on life parameters, antioxidant systems, and MAPK signaling pathways in the rotifer <i>Brachionus koreanus</i> and the copepod <i>Paracyclopina nana</i>

Lee, Young Hwan,Kim, Duck-Hyun,Kang, Hye-Min,Wang, Minghua,Jeong, Chang-Bum,Lee, Jae-Seong Elsevier 2017 Aquatic toxicology Vol.190 No.-

<P><B>Abstract</B></P> <P>To evaluate the adverse effects of MeHg on the rotifer <I>Brachionus koreanus</I> and the copepod <I>Paracyclopina nana</I>, we assessed the effects of MeHg toxicity on life parameters (e.g. growth retardation and fecundity), antioxidant systems, and mitogen-activated protein kinase (MAPK) signaling pathways at various concentrations (1ng/L, 10ng/L, 100ng/L, 500ng/L, and 1000ng/L). MeHg exposure resulted in the growth retardation with the increased ROS levels but decreased glutathione (GSH) levels in a dose-dependent manner in both <I>B. koreanus</I> and <I>P. nana</I>. Antioxidant enzymatic activities (e.g. glutathione <I>S</I>-transferase [GST], glutathione reductase [GR], and glutathione peroxidase [GPx]) in <I>B. koreanus</I> showed more positive responses compared the control but in <I>P. nana</I>, those antioxidant enzymatic activities showed subtle changes due to different no observed effect concentration (NOEC) values among the two species. Expression of antioxidant genes (e.g. superoxide dismutase [<I>SOD</I>], GSTs, glutathione peroxidase [<I>GPx</I>], and catalase [<I>CAT</I>]) also demonstrated similar effects as shown in antioxidant enzymatic activities. In <I>B. koreanus</I>, the level of p-ERK was decreased in the presence of 1000ng/L MeHg, while the levels of p-ERK and p-p38 in <I>P. nana</I> were reduced in the presence of 10ng/L MeHg. However, p-JNK levels were not altered by MeHg in <I>B. koreanus</I> and <I>P. nana</I>, compared to the corresponding controls. In summary, life parameters (e.g. reduced fecundity and survival rate) were closely associated with effects on the antioxidant system in response to MeHg. These observations provide a better understanding on the adverse effects of MeHg on in vivo life parameters and molecular defense mechanisms in <I>B. koreanus</I> and <I>P. nana</I>.</P> <P><B>Highlights</B></P> <P> <UL> <LI> MeHg retarded growth in a dose-dependent manner and increased ROS levels in a dose-dependent manner in both organisms. </LI> <LI> Antioxidant enzymatic activities revealed different tendencies between <I>P. nana</I> and <I>B. koreanus</I>. </LI> <LI> In <I>B. koreanus</I>, the level of p-ERK was decreased at 1000ng/L MeHg, while the levels of p-ERK and p-p38 in <I>P. nana</I> were reduced at 10ng/L MeHg. </LI> <LI> Antioxidant system in response to MeHg was associated with negative effects on life parameters (e.g. reduced fecundity and survival rate). </LI> </UL> </P>

5-Lipoxygenase inhibitors suppress RANKL-induced osteoclast formation via NFATcl expression

( Ju Hee Kang ),( Zheng Ting ),( Mi Ran Moon ),( Jung Seon Sim ),( Jung Min Lee ),( Kyung Eun Doh ),( Sunhye Hong ),( Minghua Cui ),( Sun Choi ),( Hyeun Wook Chang ),( Hea Young Park Choo ),( Mijung Y 영남대학교 약품개발연구소 2016 영남대학교 약품개발연구소 연구업적집 Vol.26 No.-

5-Lipoxygenase synthesizes leukotrienes from arachidonic acid. We developed three novel 5-LO inhibi-tors having a benzoxazole scaffold as a potential anti-osteoclastogenics. They significantly suppressed RANKL-induced osteoclast formation in mouse bone marrow-derived macrophages. Furthermore, one compound. K7, inhibited the bone resorptive activity of osteoclasts. The anti-osteoclastogenic effect of K7 was mainly attributable to reduction in the expression of NFATc1. an essential transcription factor for osteoclast differentiation. K7 inhibited osteoclast formation via ERK and p38 MAPK. as well as NF-KB signaling pathways. K7 reduced lipopolysaccharide (LPS)-induced osteoclast formation in vivo. corroborating the in vitro data. Thus, IG exerted an inhibitory effect on osteoclast formation in vitro and in vivo, properties that make it a potential candidate for the treatment of bone diseases associated with excessive bone resorption.