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41.
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Shreyasi Asthana Zaved Hazarika Parth Sarathi Nayak Jyoti Roy Anupam Nath Jha Bibekanand Mallick Suman Jha 《Biochimica et Biophysica Acta (BBA)/General Subjects》2019,1863(1):153-166
Background
Injection localized amyloidosis is one of the most prevalent disorders in type II diabetes mellitus (TIIDM) patients relying on insulin injections. Previous studies have reported that nanoparticles can play a role in the amyloidogenic process of proteins. Hence, the present study deals with the effect of zinc oxide nanoparticles (ZnONP) on the amyloidogenicity and cytotoxicity of insulin.Methods
ZnONP is synthesised and characterized using XRD, Zeta Sizer, UV-Visible spectroscope and TEM. The characterization is followed by ZnONP interaction with insulin, which is studied employing fluorescence spectroscopes, isothermal titration calorimetry and molecular dynamics simulations. The interaction leads insulin conformational rearrangement into amyloid-like fibril, which is studied using thioflavin T dye binding assay, circular dichroism spectroscopy and TEM, followed by cytotoxicity propensity using Alamar Blue dye reduction assay.Results
Insulin has very weak interaction with ZnONP interface. Insulin at studied concentration forms amorphous aggregates at physiological pH, whereas in presence of ZnONP interface amyloid-like fibrils are formed. While the amyloid-like fibrils are cytotoxic to MIN6 and THP-1 cell lines, insulin and ZnONP individual solutions and their fresh mixtures enhance the cells proliferation.Conclusions
The presence of ZnONP interface enhances insulin fibrillation at physiological pH by providing a favourable template for the nucleation and growth of insulin amyloids.General significance
The studied protein-nanoparticle system from protein conformational dynamics point of view throws caution over nanoparticle use in biological applications, especially in vivo applications, considering the amyloidosis a very slow but non-curable degenerative disease. 相似文献43.
Uzma Saqib Syed M. Faisal Rohit Saluja Mirza S. Baig 《Journal of cellular biochemistry》2019,120(1):452-460
The benefits associated with resveratrol (Resv; 3,4′,5-trihydroxy-trans-stilbene) are known for a long time. The therapeutic properties of Resv are observed in diseases like cancer, neurological disorders, atherosclerosis, aging, inflammation, etc. Multiple studies suggest that the beneficial properties of Resv are due to its binding to targets in multiple pathways. The same has been reflected in inflammation, where Resv has been shown to inhibit nuclear factor κ light-chain enhancer of activated B cells in the toll-like receptor 4 (TLR4) pathway. There are multiple cellular targets which bind to Resv, however the mode and the key interactions involved remain elusive for many of them. In the current work, we have investigated the structural insights of Resv with three of its binding partners involved in the inflammatory TLR4 signaling pathway. Through a structure-based modelling and molecular dynamics study, we have unraveled the molecular and atomic interactions involved in the Resv-binary complexes of inhibitor of κB kinase, cyclooxygeanse-2, and tank-binding kinase I, all three of which are key players in TLR4 inflammatory signaling. This study is the latest addition to the investigations of the structural partners of Resv and its molecular interactions. 相似文献
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Relationship between NF-kappaB and trypsinogen activation in rat pancreas after supramaximal caerulein stimulation 总被引:3,自引:0,他引:3
Hietaranta AJ Saluja AK Bhagat L Singh VP Song AM Steer ML 《Biochemical and biophysical research communications》2001,280(1):388-395
Intra-acinar cell nuclear factor-kappaB (NF-kappaB) and trypsinogen activation are early events in secretagogue-induced acute pancreatitis. We have studied the relationship between NF-kappaB and trypsinogen activation in rat pancreas. CCK analogue caerulein induces early (within 15 min) parallel activation of both NF-kappaB and trypsinogen in pancreas in vivo as well as in pancreatic acini in vitro. However, NF-kappaB activation can be induced without trypsinogen activation by lipopolysaccharide in pancreas in vivo and by phorbol ester in pancreatic acini in vitro. Stimulation of acini with caerulein after 6 h of culture results in NF-kappaB but not trypsinogen activation. Protease inhibitors (AEBSF, TLCK, and E64d) inhibit both intracellular trypsin activity and NF-kappaB activation in caerulein stimulated acini. A chymotrypsin inhibitor (TPCK) inhibits NF-kappaB activation but not trypsin activity. The proteasome inhibitor MG-132 prevents caerulein-induced NF-kappaB activation but does not prevent trypsinogen activation. These findings indicate that although caerulein-induced NF-kappaB and trypsinogen activation are temporally closely related, they are independent events in pancreatic acinar cells. NF-kappaB activation per se is not required for the development of early acinar cell injury by supramaximal secretagogue stimulation. 相似文献
47.
Mongin Alexander A.; Reddi Jyoti M.; Charniga Carol; Kimelberg Harold K. 《American journal of physiology. Cell physiology》1999,276(5):C1226
Volume-dependent anion channels permeable forCl and amino acids arethought to play an important role in the homeostasis of cell volume.Astrocytes are the main cell type in the mammalian brain showing volumeperturbations under physiological and pathophysiological conditions. Weinvestigated the involvement of tyrosine phosphorylation in hyposmoticmedium-induced[3H]taurine andD-[3H]aspartaterelease from primary astrocyte cultures. The tyrosine kinase inhibitorstyrphostin 23 and tyrphostin A51 partially suppressed thevolume-dependent release of[3H]taurine in adose-dependent manner with half-maximal effects at ~40 and 1 µM,respectively. In contrast, the release ofD-[3H]aspartatewas not significantly affected by these agents in the sameconcentration range. The inactive analog tyrphostin 1 hadno significant effect on the release of both amino acids. The dataobtained suggest the existence of at least two volume-dependent anionchannels permeable to amino acids in astrocyte cultures. One of thesechannels is permeable to taurine and is under the control of tyrosinekinase(s). The other is permeable to both taurine and aspartate, butits volume-dependent regulation does not require tyrosine phosphorylation. 相似文献
48.
Kurukulasuriya R Sorensen BK Link JT Patel JR Jae HS Winn MX Rohde JR Grihalde ND Lin CW Ogiela CA Adler AL Collins CA 《Bioorganic & medicinal chemistry letters》2004,14(9):2047-2050
Biaryl amides derived from a reported series of ureas 1 were evaluated and found to be potent human glucagon receptor antagonists. The benzofuran analogue 6i was administered in Sprague-Dawley rats and blocked the effects of an exogenous glucagon challenge. 相似文献
49.
Synaptotagmin is considered a calcium-dependent trigger for regulated exocytosis. We examined the role of synaptotagmin VII (Syt VII) in the calcium-dependent exocytosis of individual lysosomes in wild-type (WT ) and Syt VII knockout (KO ) mouse embryonic fibroblasts (MEFs) using total internal reflection fluorescence microscopy. In WT MEFs, most lysosomes only partially released their contents, their membrane proteins did not diffuse into the plasma membrane, and inner diameters of their fusion pores were smaller than 30 nm. In Syt VII KO MEFs, not only was lysosomal exocytosis triggered by calcium, but all of these restrictions on fusion were also removed. These observations indicate that Syt VII does not function as the calcium-dependent trigger for lysosomal exocytosis. Instead, it restricts the kinetics and extent of calcium-dependent lysosomal fusion. 相似文献
50.
As part of a project that aims at screening TNA-related oligonucleotide systems in which threose backbone units may have some or all of their oxygen functions replaced by nitrogen, two TNA analogs containing (2'NH)- and (3'NH)-phosphoramidate groups, respectively, in place of phosphodiester groups were synthesized. They show base-pairing properties that are very similar to those of TNA itself. We also synthesized 2',3'-diamino analogs of alpha-L-threofuranosyl mononucleosides, yet attempts to convert them to TNA analogs containing phosphodiamidate linker groups were not successful. Such 2',3'-diamino derivatives of threofuranosyl nucleosides may be of interest, however, as building blocks of TNA analogs that contain non-phosphorous linker groups. 相似文献