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Hajung Yoo Jeongmin Lee Bokwang Kim Heechang Moon Huisu Jeong Kyungmi Lee Woo Jeung Song Junho K. Hur Yohan Oh 《BMB reports》2022,55(7):323
Together with neuronal loss, the existence of insoluble inclusions of alpha-synuclein (α-syn) in the brain is widely accepted as a hallmark of synucleinopathies including Parkinson’s disease (PD), multiple system atrophy, and dementia with Lewy body. Because the α-syn aggregates are deeply involved in the pathogenesis, there have been many attempts to demonstrate the mechanism of the aggregation and its potential causative factors including post-translational modifications (PTMs). Although no concrete conclusions have been made based on the previous study results, growing evidence suggests that modifications such as phosphorylation and ubiquitination can alter α-syn characteristics to have certain effects on the aggregation process in PD; either facilitating or inhibiting fibrillization. In the present work, we reviewed studies showing the significant impacts of PTMs on α-syn aggregation. Furthermore, the PTMs modulating α-syn aggregation-induced cell death have been discussed. 相似文献
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Cell growth conditions and purification methods are important in determining biopharmaceutical activity. However, in studies aimed at manufacturing virus-like particles (VLPs) for the purpose of creating a prophylactic vaccine and antigen for human papillomavirus (HPV), the effects of the presence of a resin-bound ligand during purification have never been investigated. In this study, we compared the structural integrity and immunogenicity of two kinds of VLPs derived from HPV type 16 (HPV16 VLPs): one VLP was purified by heparin chromatography (hHPV16 VLP) and the other by cation-exchange chromatography (cHPV16 VLP). The reactivity of anti-HPV16 neutralizing monoclonal antibodies (H16.V5 and H16.E70) towards hHPV16 VLP were significantly higher than the observed cHPV16 VLP reactivities, implying that hHPV16 VLP possesses a greater number of neutralizing epitopes and has a greater potential to elicit anti-HPV16 neutralizing antibodies. After the application of heparin chromatography, HPV16 VLP has a higher affinity for H16.V5 and H16.E70. This result indicates that heparin chromatography is valuable in selecting functional HPV16 VLPs. In regard to VLP immunogenicity, the anti-HPV16 L1 IgG and neutralizing antibody levels elicited by immunizations of mice with hHPV16 VLPs were higher than those elicited by cHPV16 VLP with and without adjuvant. Therefore, the ability of hHPV16 VLP to elicit humoral immune responses was superior to that of cHPV16 VLP. We conclude that the specific chromatographic technique employed for the purification of HPV16 VLPs is an important factor in determining the structural characteristics and immunogenicity of column-purified VLPs. 相似文献
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Su Yeoun Kim Young Joo Jeon Seung Hun Oh Hyun Sook Kim Ok Joon Kim Doyeun Oh Mingull Jeung Byung Soo Shin Young Seok Park Nam Keun Kim 《Genes & genomics.》2012,34(5):485-492
Kinase insert domain receptor (KDR) gene polymorphisms are associated with coronary artery lesions. The aims of this study were to evaluate the role of KDR polymorphisms in patients susceptible to cerebral white matter lesion (cWML), and determine the relationship between KDR polymorphisms and plasma total homocysteine levels. A total of 326 study subjects who had never had a stroke were enrolled in this study. The indices of cWMLs included total WML (TWML), periventricular white matter lesion (PWML), and subcortical white matter lesion (SCWML) in brain fluid-attenuated inversion recovery images. Among the 326 study subjects, TWML was found in 65 patients (20%). Common genetic variants of KDR (?604, 1192, and 1719) were examined. In multivariate analysis, there were no significant effects of any tested KDR polymorphisms on cWML. A significant association with plasma total homocysteine levels was found for TWML. The haplotypes of the KDR -604, 1192, and 1719 polymorphisms were associated with the increased risk of development of cWML. We conclude that the haplotypes of KDR polymorphisms are associated with an increased risk of development of cWML. 相似文献
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David-Marian Otte Maria Luisa Barcena de Arellano Andras Bilkei-Gorzo ?nder Albayram Sophie Imbeault Haang Jeung Judith Alferink Andreas Zimmer 《PloS one》2013,8(6)
NMDA receptors are activated after binding of the agonist glutamate to the NR2 subunit along with a co-agonist, either L-glycine or D-serine, to the NR1 subunit. There is substantial evidence to suggest that D-serine is the most relevant co-agonist in forebrain regions and that alterations in D-serine levels contribute to psychiatric disorders. D-serine is produced through isomerization of L-serine by serine racemase (Srr), either in neurons or in astrocytes. It is released by astrocytes by an activity-dependent mechanism involving secretory vesicles. In the present study we generated transgenic mice (SrrTg) expressing serine racemase under a human GFAP promoter. These mice were biochemically and behaviorally analyzed using paradigms of anxiety, depression and cognition. Furthermore, we investigated the behavioral effects of long-term administration of D-serine added to the drinking water. Elevated brain D-serine levels in SrrTg mice resulted in specific behavioral phenotypes in the forced swim, novelty suppression of feeding and olfactory bulbectomy paradigms that are indicative of a reduced proneness towards depression-related behavior. Chronic dietary D-serine supplement mimics the depression-related behavioral phenotype observed in SrrTg mice. Our results suggest that D-serine supplementation may improve mood disorders. 相似文献
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Kyung-Chul?Choi Peter?CK?Leung Eui-Bae?JeungEmail author 《Reproductive biology and endocrinology : RB&E》2005,3(1):66
Although Calbindin-D9k (CaBP-9k), a cytosolic calcium binding protein which has calcium binding sites, is expressed in various
tissues, i.e., intestine, uterus, and placenta, potential roles of this gene and its protein are not clearly understood. Uterine
CaBP-9k may be involved in controlling myometrial activity related with intracellular calcium level and is not under the control
of vitamin D despite the presence of vitamin D receptors. But, it is under the control of the sex steroid hormones, estrogen
(E2) and progesterone (P4), in female reproductive systems including the uterus and placenta. Thus, in this review, we summarize
recent research literature in regards to the expression and regulation of CaBP-9k in mammals and introduce the research data
of recent studies by us and others. 相似文献
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Cyclosporine A (CsA) is a powerful immunosuppressive drug with side effects including the development of chronic nephrotoxicity. In this study, we investigated CsA treatment induced apoptotic and autophagic cell death in pituitary GH3 cells. CsA treatment (0.1 to 10 µM) decreased survival of GH3 cells in a dose-dependent manner. Cell viability decreased significantly with increasing CsA concentrations largely due to an increase in apoptosis, while cell death rates due to autophagy altered only slightly. Several molecular and morphological features correlated with cell death through these distinct pathways. At concentrations ranging from 1.0 to 10 µM, CsA induced a dose-dependent increase in expression of the autophagy markers LC3-I and LC3-II. Immunofluorescence staining revealed markedly increased levels of both LC3 and lysosomal-associated membrane protein 2 (Lamp2), indicating increases in autophagosomes. At the same CsA doses, apoptotic cell death was apparent as indicated by nuclear and DNA fragmentation and increased p53 expression. In apoptotic or autophagic cells, p-ERK levels were highest at 1.0 µM CsA compared to control or other doses. In contrast, Bax levels in both types of cell death were increased in a dose-dependent manner, while Bcl-2 levels showed dose-dependent augmentation in autophagy and were decreased in apoptosis. Manganese superoxide dismutase (Mn-SOD) showed a similar dose-dependent reduction in cells undergoing apoptosis, while levels of the intracellular calcium ion exchange maker calbindin-D9k were decreased in apoptosis (1.0 to 5 µM CsA), but unchanged in autophagy. In conclusion, these results suggest that CsA induction of apoptotic or autophagic cell death in rat pituitary GH3 cells depends on the relative expression of factors and correlates with Bcl-2 and Mn-SOD levels. 相似文献
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