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David Yang-Wei Fann Yun-An Lim Yi-Lin Cheng Ker-Zhing Lok Prasad Chunduri Sang-Ha Baik Grant R. Drummond S. Thameem Dheen Christopher G. Sobey Dong-Gyu Jo Christopher Li-Hsian Chen Thiruma V. Arumugam 《Molecular neurobiology》2018,55(2):1082-1096
Multi-protein complexes, termed “inflammasomes,” are known to contribute to neuronal cell death and brain injury following ischemic stroke. Ischemic stroke increases the expression and activation of nucleotide-binding oligomerization domain (NOD)-like receptor (NLR) Pyrin domain containing 1 and 3 (NLRP1 and NLRP3) inflammasome proteins and both interleukin (IL)-1β and IL-18 in neurons. In this study, we provide evidence that activation of either the NF-κB and MAPK signaling pathways was partly responsible for inducing the expression and activation of NLRP1 and NLRP3 inflammasome proteins and that these effects can be attenuated using pharmacological inhibitors of these two pathways in neurons and brain tissue under in vitro and in vivo ischemic conditions, respectively. Moreover, these findings provided supporting evidence that treatment with intravenous immunoglobulin (IVIg) preparation can reduce activation of the NF-κB and MAPK signaling pathways resulting in decreased expression and activation of NLRP1 and NLRP3 inflammasomes, as well as increasing expression of anti-apoptotic proteins, Bcl-2 and Bcl-xL, in primary cortical neurons and/or cerebral tissue under in vitro and in vivo ischemic conditions. In summary, these results provide compelling evidence that both the NF-κB and MAPK signaling pathways play a pivotal role in regulating the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons and brain tissue under ischemic conditions. In addition, treatment with IVIg preparation decreased the activation of the NF-κB and MAPK signaling pathways, and thus attenuated the expression and activation of NLRP1 and NLRP3 inflammasomes in primary cortical neurons under ischemic conditions. Hence, these findings suggest that therapeutic interventions that target inflammasome activation in neurons may provide new opportunities in the future treatment of ischemic stroke. 相似文献
3.
Yoonkyung Park Baik Hwang Byoungsik Pyo Hyeonsook Cheong 《Biotechnology and Bioprocess Engineering》1997,2(1):15-18
We intended to examine the expression of the T-cell growth factor (human interleukin-2) so that a binary vector, pSSK-1, carrying
the IL-2 gene was constructed and transferred intoA. tumefaciens for the purpose of the transformation of the potato (Solanum tuberosum cv. Superior). All of theAgrobacterium-infected potato explants were regenerated to shoots in modified MS medium and 81% of them rooted on the medium containing
kanamycin (200 mg/L). Southern and Northern analysis were performed to verify the transformation events. EL-ISA test indicated
that IL-2 protein was produced from IL-2-transformed potatoes. These results suggested expression and production of the IL-2
protein from the transgenic potato. 相似文献
4.
Woo HN Baik SH Park JS Gwon AR Yang S Yun YK Jo DG 《Biochemical and biophysical research communications》2011,(1):402-15
Accumulation of amyloid-β (Aβ) is widely accepted as the key instigator of Alzheimer’s disease (AD). The proposed mechanism is that accumulation of Aβ results in inflammatory responses, oxidative damages, neurofibrillary tangles and, subsequently, neuronal/synaptic dysfunction and neuronal loss. Given the critical role of Aβ in the disease process, the proteases that produce this peptide are obvious targets. The goal would be to develop drugs that can inhibit the activity of these targets. Protease inhibitors have proved very effective for treating other disorders such as AIDS and hypertension. Mutations in APP (amyloid-β precursor protein), which flanks the Aβ sequence, cause early-onset familial AD, and evidence has pointed to the APP-to-Aβ conversion as a possible therapeutic target. Therapies aimed at modifying Aβ-related processes aim higher up the cascade and are therefore more likely to be able to alter the progression of the disease. However, it is not yet fully known whether the increases in Aβ levels are merely a result of earlier events that were already causing the disease. 相似文献
5.
The endoplasmic reticulum (ER) plays essential roles indispensable for cellular activity and survival, including functions such as protein synthesis, secretory and membrane protein folding, and Ca2+ release in cells. The ER is sensitive to stresses that can lead to the aggregation and accumulation of misfolded proteins, which eventually triggers cellular dysfunction; severe or prolonged ER stress eventually induces apoptosis. ER stress-induced apoptosis causes several devastating diseases such as atherosclerosis, neurodegenerative diseases, and diabetes. In addition, the production of biopharmaceuticals such as monoclonal antibodies requires the maintenance of normal ER functions to achieve and maintain the production of high-quality products in good quantities. Therefore, it is necessary to develop methods to efficiently relieve ER stress and protect cells from ER stress-induced apoptosis. The silkworm storage protein 1 (SP1) has anti-apoptotic activities that inhibit the intrinsic mitochondrial apoptotic pathway. However, the role of SP1 in controlling ER stress and ER stress-induced apoptosis has not been investigated. In this paper, we demonstrate that SP1 can inhibit apoptosis induced by a well-known ER stress inducer, thapsigargin, by alleviating the decrease in cell viability and mitochondrial membrane potential. Interestingly, SP1 significantly blocked increases in CHOP and GRP78 expression as well as ER Ca2+ leakage into the cytosol following ER stress induction. This indicates that SP1 protects cells from ER stressinduced apoptosis by functioning as an upstream inhibitor of apoptosis. Therefore, studying SP1 function can offer new insights into protecting cells against ER stress-induced apoptosis for future applications in the biopharmaceutical and medicine industries. 相似文献
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7.
Keun Sik Baik Yeoung Min Hwang Jong-Soon Choi Joseph Kwon Chi Nam Seong 《Antonie van Leeuwenhoek》2013,104(6):1143-1150
A motile, curved to twisted rod-shaped aerobic bacterium, designated strain 04SU4-PT, was isolated from freshwater collected from the Woopo wetland (Republic of Korea). Cells were observed to be Gram-stain negative, catalase negative and oxidase positive. The major fatty acids (>10 % of the total) were identified as C19:0 ω8c cyclo (24.6 %), C16:0 (24.3 %) and C18:1 ω7c (13.1 %). The DNA G+C content was determined to be 71.5 mol%. The major polar lipids were identified as phosphatidylglycerol, phosphatidylethanolamine, one unknown phospholipid and one unknown aminolipid. The major ubiquinone was determined to be Q-10. A phylogenetic tree based on 16S rRNA gene sequences showed that strain 04SU4-PT forms an evolutionary lineage within the genus Dongia and its nearest neighbour is Dongia mobilis LM22T (98.0 % sequence similarity). Genomic DNA–DNA hybridization of stain 04SU4-PT with D. mobilis LM22T showed relatedness of only 34.2 %. The phenotypic characteristics indicate the strain 04SU4-PT can be distinguished from the sole member of the genus Dongia. On the basis of the data presented in this study, strain 04SU4-PT represents a novel species, for which the name Dongia rigui is proposed. The type strain is 04SU4-PT (KCTC 23341T = JCM 17521T). 相似文献
8.
Jun Park Yong Hwa Jo Chang Hoon Cho Wonchae Choe Insug Kang Hyung Hwan Baik Kyung-Sik Yoon 《Biochemical and biophysical research communications》2013,430(1):429-435
DNA DSBs are induced by IR or radiomimetic drugs such as doxorubicin. It has been indicated that cells from ataxia-telangiectasia patients are highly sensitive to radiation due to defects in DNA repair, but whether they have impairment in apoptosis has not been fully elucidated. A-T cells showed increased sensitivity to high levels of DNA damage, however, they were more resistant to low doses. Normal cells treated with combination of KU55933, a specific ATM kinase inhibitor, and doxorubicin showed increased resistance as they do in a similar manner to A-T cells. A-T cells have higher viability but more DNA breaks, in addition, the activations of p53 and apoptotic proteins (Bax and caspase-3) were deficient, but Akt expression was enhanced. A-T cells subsequently underwent premature senescence after treatment with a low dose of doxorubicin, which was confirmed by G2 accumulation, senescent morphology, and SA-β-gal positive until 15 days repair incubation. Finally, A-T cells are radio-resistant at low doses due to its defectiveness in detecting DNA damage and apoptosis, but the accumulation of DNA damage leads cells to premature senescence. 相似文献
9.
Yoon Dae Wui Hong Il-Hee Baik Inkyung Shin Hyun-Woo 《Sleep and biological rhythms》2019,17(3):297-304
Sleep and Biological Rhythms - There is an increasing need for portable sleep monitoring in clinical practice, but there is no comparative study that used the same device for home and in-laboratory... 相似文献
10.
Jang HD Chung YM Baik JH Choi YG Park IS Jung YK Lee SY 《Biochemical and biophysical research communications》2001,281(2):499-505
Tumor necrosis factor (TNF) signaling leads to pleiotropic responses in a wide range of cell types, in part by activating antiapoptotic and proapoptotic pathways. Previous studies have suggested that TNF receptor-associated factor (TRAF) 2 can mediate crucial antiapoptotic signals during TNF stimulation. However, it is unclear how the antiapoptotic signals via TRAF2 in TNF-R1 signaling is regulated. Here we show that TRAF1 is cleaved by caspase-8 into two fragments during apoptosis induced by TNF. Overexpression of the C-terminal cleavage product, TRAF1-c, increased TNF-induced cell death of hybridoma T cells. Importantly, we demonstrate that the cleavage product of TRAF1 coimmunoprecipitates with TRAF2 that is released from the TNF-R1 complex in response to prolonged TNF treatment. These results indicate that caspase-dependent cleavage of TRAF1 generates TRAF1-c fragments that are able to bind TRAF2, and then sequester TRAF2 from the TNF-R1 complex, rendering cells, at least in part, sensitive to TNF. 相似文献