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991.
Leem JY Vijayan S Han P Cai D Machura M Lopes KO Veselits ML Xu H Thinakaran G 《The Journal of biological chemistry》2002,277(21):19236-19240
Proteolytic processing of amyloid precursor protein generates beta-amyloid (Abeta) peptides that are deposited in senile plaques in brains of aged individuals and patients with Alzheimer's disease. Presenilins (PS1 and PS2) facilitate the final step in Abeta production, the intramembranous gamma-secretase cleavage of amyloid precursor protein. Biochemical and pharmacological evidence support a catalytic or accessory role for PS1 in gamma-secretase cleavage, as well as a regulatory role in select membrane protein trafficking. In this report, we demonstrate that PS1 is required for maturation and cell surface accumulation of nicastrin, an integral component of the multimeric gamma-secretase complex. Using kinetic labeling studies we show that in PS1(-/-)/PS2(-/-) cells nicastrin fails to reach the medial Golgi compartment, and as a consequence, is incompletely glycosylated. Stable expression of human PS1 restores these deficiencies in PS1(-/-) fibroblasts. Moreover, membrane fractionation studies show co-localization of PS1 fragments with mature nicastrin. These results indicate a novel chaperone-type role for PS1 and PS2 in facilitating nicastrin maturation and transport in the early biosynthetic compartments. Our findings are consistent with PS1 influencing gamma-secretase processing at multiple steps, including maturation and intracellular trafficking of substrates and component(s) of the gamma-secretase complex. 相似文献
992.
Wi-Sun Ryu Keun-Sik Hong Sang-Wuk Jeong Jung E. Park Beom Joon Kim Joon-Tae Kim Kyung Bok Lee Tai Hwan Park Sang-Soon Park Jong-Moo Park Kyusik Kang Yong-Jin Cho Hong-Kyun Park Byung-Chul Lee Kyung-Ho Yu Mi Sun Oh Soo Joo Lee Jae Guk Kim Jae-Kwan Cha Dae-Hyun Kim Jun Lee Moon-Ku Han Man Seok Park Kang-Ho Choi Juneyoung Lee Jeffrey L. Saver Eng H. Lo Hee-Joon Bae Dong-Eog Kim 《PLoS medicine》2022,19(2)
BackgroundPreclinical data suggest circadian variation in ischemic stroke progression, with more active cell death and infarct growth in rodent models with inactive phase (daytime) than active phase (nighttime) stroke onset. We aimed to examine the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in human ischemic stroke.Methods and findingsIn a Korean nationwide multicenter observational cohort study from May 2011 to July 2020, we assessed circadian effects on initial stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at admission), END, and favorable functional outcome (3-month modified Rankin Scale [mRS] score 0 to 2 versus 3 to 6). We included 17,461 consecutive patients with witnessed ischemic stroke within 6 hours of onset. Stroke onset time was divided into 2 groups (day-onset [06:00 to 18:00] versus night-onset [18:00 to 06:00]) and into 6 groups by 4-hour intervals. We used mixed-effects ordered or logistic regression models while accounting for clustering by hospitals. Mean age was 66.9 (SD 13.4) years, and 6,900 (39.5%) were women. END occurred in 2,219 (12.7%) patients. After adjusting for covariates including age, sex, previous stroke, prestroke mRS score, admission NIHSS score, hypertension, diabetes, hyperlipidemia, smoking, atrial fibrillation, prestroke antiplatelet use, prestroke statin use, revascularization, season of stroke onset, and time from onset to hospital arrival, night-onset stroke was more prone to END (adjusted incidence 14.4% versus 12.8%, p = 0.006) and had a lower likelihood of favorable outcome (adjusted odds ratio, 0.88 [95% CI, 0.79 to 0.98]; p = 0.03) compared with day-onset stroke. When stroke onset times were grouped by 4-hour intervals, a monotonic gradient in presenting NIHSS score was noted, rising from a nadir in 06:00 to 10:00 to a peak in 02:00 to 06:00. The 18:00 to 22:00 and 22:00 to 02:00 onset stroke patients were more likely to experience END than the 06:00 to 10:00 onset stroke patients. At 3 months, there was a monotonic gradient in the rate of favorable functional outcome, falling from a peak at 06:00 to 10:00 to a nadir at 22:00 to 02:00. Study limitations include the lack of information on sleep disorders and patient work/activity schedules.ConclusionsNight-onset strokes, compared with day-onset strokes, are associated with higher presenting neurologic severity, more frequent END, and worse 3-month functional outcome. These findings suggest that circadian time of onset is an important additional variable for inclusion in epidemiologic natural history studies and in treatment trials of neuroprotective and reperfusion agents for acute ischemic stroke.Wi-Sun Ryu and colleagues investigate the association of stroke onset time with presenting severity, early neurological deterioration (END), and long-term functional outcome in ischemic stroke. 相似文献
993.
Mi‐Kyung Han Xiaoyuen Zhou Ctirad Uher Sung‐Jin Kim Mercouri G. Kanatzidis 《Liver Transplantation》2012,2(10):1218-1225
The effects of Cd‐doping on the thermoelectric properties of Sn1–xPbxTe are investigated and compared to the properties of the corresponding Sn1–xPbxTe solid solutions. The addition of Cd results in a reduction in the carrier concentration and changes in the physical properties, as well as in the conduction type of Sn1–xPbxTe. A significant increase in the power factor accompanied by a reduction in the thermal conductivity result in a higher figure of merit (ZT) for (Sn1–xPbx)0.97Cd0.03Te than that of undoped Sn1–xPbxTe. The maximum ZT (~0.7) values are observed for p‐type material with x = 0.36 at 560 K. Much higher values (ZT ~ 1.2 at 560 K for x = 0.73) are obtained on n‐type samples. 相似文献
994.
Bacterial lipoproteins play an important role in bacterial pathogenesis and physiology. The genome of Campylobacter jejuni, a major foodborn pathogen, is predicted to contain over 20 lipoproteins. However, the functions of the majority of C. jejuni lipoproteins remain unknown. The Cj0090 protein is encoded by a lipoprotein operon composed of cj0089, cj0090, and cj0091. Here, we report the crystal structure of Cj0090 at 1.9 Å resolution, revealing a novel variant of the immunoglobulin fold with β‐sandwich architecture. The structure suggests that Cj0090 may be involved in protein‐protein interactions, consistent with a possible role for bacterial lipoproteins. Proteins 2012;. © 2012 Wiley Periodicals, Inc. 相似文献
995.
Jun Seo Goo Yo Na Kim Kyung Mi Choi In Sik Hwang Ji Eun Kim Young Ju Lee Moon Hwa Kwak Sun Bo Shim Seung Wan Jee Chul Joo Lim Je Kyung Seong Dae Youn Hwang 《Clinical proteomics》2013,10(1):10
Background
To characterize changes in global protein expression in kidneys of transgenic rats overexpressing human selenoprotein M (SelM) in response to increased bioabivility of selenium (Sel), total proteins extracted from kidneys of 10-week-old CMV/hSelM Tg and wild-type rats were separated by 2-dimensional gel electrophoresis and measured for changes in expression.Results
Ten and three proteins showing high antioxidant enzymatic activity were up- and down-regulated, respectively, in SelM-overexpressing CMV/hSelM Tg rats compared to controls based on an arbitrary 2-fold difference. Up-regulated proteins included LAP3, BAIAP2L1, CRP2, CD73 antigen, PDGF D, KIAA143 homolog, PRPPS-AP2, ZFP313, HSP-60, and N-WASP, whereas down-regulated proteins included ALKDH3, rMCP-3, and STC-1. After Sel treatment, five of the up-regulated proteins were significantly increased in expression in wild-type rats, whereas there were no changes in CMV/hSelM Tg rats. Only two of the down-regulated proteins showed reduced expression in wild-type and Tg rats after Sel treatment.Conclusions
These results show the primary novel biological evidences that new functional protein groups and individual proteins in kidneys of Tg rats relate to Sel biology including the response to Sel treatment and SelM expression. 相似文献996.
Huiyun Seo In-Seon Lee Jae Eun Park Sung Goo Park Do Hee Lee Byoung Chul Park Sayeon Cho 《PloS one》2013,8(11)
Protein tyrosine phosphatases play key roles in a diverse range of cellular processes such as differentiation, cell proliferation, apoptosis, immunological signaling, and cytoskeletal function. Protein tyrosine phosphatase non-receptor type 7 (PTPN7), a member of the phosphatase family, specifically inactivates mitogen-activated protein kinases (MAPKs). Here, we report that PTPN7 acts as a regulator of pro-inflammatory TNF-α production in RAW 264.7 cells that are stimulated with lipopolysaccharide (LPS) that acts as an endotoxin and elicits strong immune responses in animals. Stimulation of RAW 264.7 cells with LPS leads to a transient decrease in the levels of PTPN7 mRNA and protein. The overexpression of PTPN7 inhibits LPS-stimulated production of TNF-α. In addition, small interfering RNA (siRNA) analysis showed that knock-down of PTPN7 in RAW 264.7 cells increased TNF-α production. PTPN7 has a negative regulatory function to extracellular signal regulated kinase 1/2 (ERK1/2) and p38 that increase LPS-induced TNF-α production in macrophages. Thus, our data presents PTPN7 as a negative regulator of TNF-α expression and the inflammatory response in macrophages. 相似文献
997.
998.
Kim DH Kim JM Lee EK Choi YJ Kim CH Choi JS Kim ND Yu BP Chung HY 《The Journal of nutritional biochemistry》2012,23(10):1277-1284
Baicalin is a flavonoid known to modify various redox-related biological activities. Included is its ability to suppress reactive species (RS) producing activity and modulate nuclear factor-κB through cellular redox regulation with enhanced thiol ability. FoxO regulates various genes that are known to be involved in cellular metabolism related to cell death and the oxidative stress response. One such case is the prevention of FoxO1 expression by activated insulin-induced phosphatidylinositol 3-kinase (PI3K)/Akt, which leads to increased oxidative stress and aging processes. In the present study, we attempted to elucidate the molecular modulation of antioxidant baicalin on the insulin-induced FoxO1 inactivation. We used HEK293T cultured cells and kidney tissue isolated from 24-month-old rats treated with baicalin at a dose of 10 or 20 mg/kg/day for 10 days. We found that baicalin enhanced catalase and suppressed RS production in cell system and in isolated kidney tissue in contrast to the nontreated aged rats. Results also showed activation of insulin signaling (PI3K/Akt), FoxO1 phosphorylation/acetylation and the down-regulation of catalase and manganese superoxide dismutase, both of which are FoxO1-targeting genes. Furthermore, baicalin-treated rats showed a decreased FoxO1 phosphorylation via PI3K/Akt cascade and FoxO1 acetylation by the cAMP-response element-binding protein binding protein (CBP). These results strongly suggest that treatment with baicalin influenced phosphorylation/acetylation of FoxO1 by up-regulating PI3K/Akt signaling through insulin in aged rats. Our results further reveal that baicalin regulated FoxO1 phosphorylation via PI3K/Akt by insulin and FoxO1 acetylation by the interaction of CBP and SIRT1, leading to changes in catalase gene expression during aging. 相似文献
999.
Zhong‐Ji Qian Kyong‐Hwa Kang BoMi Ryu Se‐Kwon Kim Jae‐Young Je Soo‐Jin Heo Chulhong Oh Do‐Hyung Kang Won Sun Park Il‐Whan Choi 《Journal of phycology》2012,48(2):475-482
Microalgae are major primary producers of organic matter in aquatic environments through their photosynthetic activities. Fermented microalga (Pavlova lutheri Butcher) preparation (FMP) is the product of yeast fermentation by Hansenula polymorpha. It was tested for the antioxidant activities including lipid peroxidation inhibitory activity, free‐radical‐scavenging activity, inhibition of reactive oxygen species (ROS) on mouse macrophages (RAW264.7 cell), and inhibited myeloperoxidase (MPO) activity in human myeloid cells (HL60). FMP exhibited the highest antioxidant activity on free‐radical scavenging, inhibitory intracellular ROS, and inhibited MPO activity. MTT [3‐(4,5‐dimethyl‐2‐yl)‐2,5‐diphenyltetrazolium bromide] assay showed no cytotoxicity in mouse macrophages (RAW264.7 cell), human myeloid cells (HL60), and human fetal lung fibroblast cell line (MRC‐5). Furthermore, the antioxidative mechanism of FMP was evaluated by protein expression levels of antioxidant enzyme (superoxide dismutase [SOD] and glutathione [GSH]) using Western blot. The results obtained in the present study indicated that FMP is a potential source of natural antioxidant. 相似文献