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31.
Ningmei Wang Aimeng Ji Abolfazl Masoudi Shuang Li Yuhong Hu Yefei Zhang Zhijun Yu Han Wang Hui Wang Jingze Liu 《Insect Science》2023,30(3):725-740
Ticks are external parasitic arthropods that can transmit a variety of pathogens by sucking blood. Low-temperature tolerance is essential for ticks to survive during the cold winter. Exploring the protein regulation mechanism of low-temperature tolerance of Haemaphysalis longicornis could help to explain how ticks survive in winter. In this study, the quantitative proteomics of several tissues of H. longicornis exposed to low temperature were studied by data independent acquisition technology. Totals of 3 699, 3 422, and 1 958 proteins were identified in the salivary gland, midgut, and ovary, respectively. The proteins involved in energy metabolism, cell signal transduction, protein synthesis and repair, and cytoskeleton synthesis changed under low-temperature stress. The comprehensive analysis of the protein regulation of multiple tissues of female ticks exposed to low temperature showed that maintaining cell homeostasis, maintaining cell viability, and enhancing cell tolerance were the most important means for ticks to maintain vital signs under low temperature. The expression of proteins involved in and regulating the above cell activities was the key to the survival of ticks under low temperatures. Through the analysis of a large amount of data, we found that the expression levels of arylamine N-acetyltransferase, inositol polyphosphate multikinase, and dual-specificity phosphatase were up-regulated under low temperature. We speculated that they might have important significance in low-temperature tolerance. Then, we performed RNA interference on the mRNA of these 3 proteins, and the results showed that the ability of female ticks to tolerate low temperatures decreased significantly. 相似文献
32.
Neda Masoudi Pablo Ibanez-Cruceyra Sarah-Lena Offenburger Alexander Holmes Anton Gartner 《PLoS genetics》2014,10(12)
Parkinson''s disease (PD), the second most prevalent neurodegenerative disease after Alzheimer''s disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling. 相似文献
33.
Raheleh Masoudi Maria S. Ioannou Michael D. Coughlin Promila Pagadala Kenneth E. Neet Oliver Clewes Shelley J. Allen David Dawbarn Margaret Fahnestock 《The Journal of biological chemistry》2009,284(27):18424-18433
Nerve growth factor (NGF) is produced as a precursor called pro-nerve growth factor (proNGF), which is secreted by many tissues and is the predominant form of NGF in the central nervous system. In Alzheimer disease brain, cholinergic neurons degenerate and can no longer transport NGF as efficiently, leading to an increase in untransported NGF in the target tissue. The protein that accumulates in the target tissue is proNGF, not the mature form. The role of this precursor is controversial, and both neurotrophic and apoptotic activities have been reported for recombinant proNGFs. Differences in the protein structures, protein expression systems, methods used for protein purification, and methods used for bioassay may affect the activity of these proteins. Here, we show that proNGF is neurotrophic regardless of mutations or tags, and no matter how it is purified or in which system it is expressed. However, although proNGF is neurotrophic under our assay conditions for primary sympathetic neurons and for pheochromocytoma (PC12) cells, it is apoptotic for unprimed PC12 cells when they are deprived of serum. The ratio of tropomyosin-related kinase A to p75 neurotrophin receptor is low in unprimed PC12 cells compared with primed PC12 cells and sympathetic neurons, altering the balance of proNGF-induced signaling to favor apoptosis. We conclude that the relative level of proNGF receptors determines whether this precursor exhibits neurotrophic or apoptotic activity.Nerve growth factor (NGF)3 regulates neuronal survival, neurite outgrowth, and differentiation in the peripheral and central nervous systems (1). The mature form of NGF forms a non-covalent homodimer and binds with high affinity (kd ≈ 10−11 m) to tropomyosin-related kinase A (TrkA) and with low affinity (kd ≈ 10−9 m) to the common neurotrophin receptor p75NTR (p75 neurotrophin receptor) (2). NGF promotes cell survival and growth in cells expressing TrkA through activation of the phosphatidylinositol 3-kinase/AKT pathway and the Ras/mitogen-activated protein kinase (MAPK) pathway (3, 4). p75NTR plays diverse roles, ranging from cell survival to cell death depending on the cellular context in which it is expressed. Through activation of the NF-κB pathway, p75NTR can contribute to cell survival in sensory neurons (5), it is involved in axonal growth via regulation of Rho activity (6), and it can interact with Trks to enhance neurotrophin affinity (at low concentration of ligand) and specificity of binding to Trks (7–9). High levels of p75NTR expression can induce apoptosis when there are low levels of Trk or when Trk is absent (10, 11). Apoptosis occurs through increased ceramide production (12), activation of c-Jun N-terminal kinase (JNK1), and p53 (10, 13). p75NTR requires a co-receptor called sortilin to induce cell death (14).NGF is produced as a precursor called pro-nerve growth factor (proNGF) (15). ProNGF is secreted by many tissues such as prostate cells, spermatids, hair follicles, oral mucosal keratinocytes, sympathetic neurons, cortical astrocytes, heart, and spleen (16–20). ProNGF is the predominant form of NGF in the central and peripheral nervous systems, whereas little or no mature NGF can be detected (21–24). In Alzheimer disease brain, retrograde transport from the cortex and hippocampus to basal forebrain cholinergic neurons is reduced as these neurons degenerate, with concomitant proNGF accumulation in the cortex and hippocampus (21, 23). This suggested that proNGF mediates biological activity besides its prodomain function of promoting protein folding and regulation of neurotrophin secretion (25–28). To study the role of proNGF protein in vitro, point mutations were inserted at the cleavage site used by furin, a proprotein convertase known to cleave proNGF (29), to minimize the conversion of proNGF to mature NGF. The resulting recombinant, cleavage-resistant proNGFs reportedly exhibit either apoptotic activity (30, 31) or neurotrophic activity (32, 33). These recombinant proteins differ in several ways (ProNGF(R−1G) ProNGFhis ProNGFE ProNGF123 WT-NGFhis Mutations −1 (R to G) −2 and −1 (RR to AA), 118 and 119 (RR to AA) −1 and +1 (RS to AA) −73 and −72 (RR to AA), −43 and −42 (KKRR to KAAR), −2 and −1 (KR to AA) None: cleavable proNGF Tag No tag Histidine tag No tag No tag Histidine tag Expression system Insect cells Insect cells, mammalian cells Bacteria Insect cells Insect cells, mammalian cells Purification No purification Nickel column Refolded from inclusion bodies, FPLC Cation exchange chromatography, immunoaffinity chromatography Nickel column