Search results for: Calreticulin
#33631298 2021/02/22 To Up
Tauroursodeoxycholic acid attenuates cisplatin-induced ototoxicity by inhibiting the accumulation and aggregation of unfolded or misfolded proteins in the endoplasmic reticulum.Cisplatin-induced ototoxicity is one of the important reasons that limit the drug's clinical application, and its mechanism has not been fully elucidated so far. The aim of this study was to explore the attenuate effect of tauroursodeoxycholic acid (TUDCA), a proteostasis promoter, on cisplatin-induced ototoxicity in vivo and in vitro, and to explore its possible mechanism. Auditory brainstem response (ABR) was measured to identify the attenuate effects of TUDCA administered subcutaneously [500 mg/kg/d × 3d, cisplatin: 4.6 mg/kg/d × 3d, intraperitoneal injection (i.p.)] or trans-tympanically (0.5 mg/mL, cisplatin: 12 mg/kg, i.p. with a pump) in Sprague-Dawley (SD) rats subjected to cisplatin-induced hearing loss. The cochlear explants of neonatal rats and OC1 auditory hair cell-like cell lines cultured in vitro were used to observe the number of apoptotic cells and the endoplasmic reticulum (ER) stress in the control, cisplatin (5 μM for 48 h for cochlear explants, 10 μM for 24 h for OC1 cells), and cisplatin + TUDCA (1 mM for 24 h for cochlear explants, 1.6 mM for 24 h for OC1 cells) groups. Differences in the expression of key proteins in the ER protein quality control (ERQC) system were detected. The changes in the attenuate effect of TUDCA on cisplatin-induced ototoxicity after down-regulating calreticulin (CRT), UDP-glucose ceramide glucosyltransferase-like 1 (UGGT1), and OS9 ER lectin (OS9) were also measured. The effect of TUDCA (10 mM) on stabilizing unfolded or misfolded proteins (UFP/MFP) was analyzed in a cell-free 0.2% bovine serum albumin (BSA) aggregation system in vitro. Both the subcutaneous and trans-tympanic TUDCA administration alleviated cisplatin-induced increase in ABR thresholds in rats. TUDCA was able to reduce cisplatin-induced apoptosis and alleviate ER stress in cochlear explants and OC1 cells. Under the cisplatin treatment, the expression levels of CRT, UGGT1, and OS9 in the auditory hair cell increased, and the expression of total ubiquitinated proteins decreased. TUDCA attenuated the effect of cisplatin on UGGT1 and OS9, and recovered the protein ubiquitination levels. After down-regulating CRT, UGGT1, or OS9, the protective effect of TUDCA decreased. In the cell-free experimental system, TUDCA inhibited the aggregation of denatured BSA molecules. In summary, TUDCA can attenuate cisplatin-induced ototoxicity, possibly by inhibiting the accumulation and aggregation of UFP/MFP and the associated ER stress.
Yingying Wen, Shimin Zong, Tianyi Liu, Peiyu Du, Hao Li, Hongjun Xiao
2373 related Products with: Tauroursodeoxycholic acid attenuates cisplatin-induced ototoxicity by inhibiting the accumulation and aggregation of unfolded or misfolded proteins in the endoplasmic reticulum.11mg1 mg
#33621788 2021/02/13 To Up
Elevated levels of oxidized nucleosides in individuals with the JAK2V617F mutation from a general population study.It is unknown if the somatic mutations in chronic myeloproliferative neoplasms (MPNs), JAK2V617F and Calreticulin, are associated with oxidative stress, or impaired mitochondrial defense against reactive oxygen species. In the Danish General Suburban Population Study (GESUS), including 116 JAK2V617F-mutated, 8 CALR-mutated, and 3310 mutation-negative participants without overt MPN, and in a study of 39 patients with myelofibrosis, the most advances type of MPNs, and 179 matched controls, we compared the urinary concentration of oxidized nucleosides - 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo) - as markers of oxidative stress. In GESUS, we performed Mendelian randomization analyses, using the Ala16Val single nucleotide polymorphism in the superoxide dismutase2 (SOD2) gene. In the multivariate analyses in GESUS, the 8-oxodG and 8-oxoGuo concentration were 13% (95%CI: 6-21%, p < 0.001) and 6% (95%CI: 0.4-11%, p = 0.035) higher in mutation-positive than in mutation-negative participants, respectively. Each SOD2 T allele was associated with an odds ratio of being mutation-positive of 1.69 (95%CI: 1.12-2.55, p = 0.013) through 8-oxodG. The 8-oxodG and 8-oxoGuo concentrations were 77% (95%CI: 49-110%, p < 0.001) and 105% (95%CI: 80-133%, p < 0.001) higher in myelofibrosis patients than in controls, respectively. In conclusion, an impaired mitochondrial antioxidative defense, that is causatively associated with markers of oxidative stress, may contribute to the development of mutations associated with MPNs.
Anders L Sørensen, Hans C Hasselbalch, Mads Emil Bjørn, Claus H Nielsen, Sabrina Cordua, Vibe Skov, Lasse Kjær, Henrik E Poulsen, Christina Ellervik
1587 related Products with: Elevated levels of oxidized nucleosides in individuals with the JAK2V617F mutation from a general population study.1 100ul1 mg100 μg
#33612174 2020/11/05 To Up
Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions.Exosomes are extracellular vesicles that mediate transport of nucleic acids, proteins, and other molecules. Prior work has implicated exosomes in the transmission of radiation nontargeted effects. Here we investigate the ability of energetic heavy ions, representative of species found in galactic cosmic rays, to stimulate exosome release from human bronchial epithelial cells in vitro. Immortalized human bronchial epithelial cells (HBEC3-KT F25F) were irradiated with 1.0 Gy of high linear energy transfer (LET) Ti, Si, or O ions, or with 10 Gy of low-LET reference γ-rays, and extracellular vesicles were collected from conditioned media. Preparations were characterized by single particle tracking analysis, transmission electron microscopy, and immunoblotting for the exosomal marker, TSG101. Based on TSG101 levels, irradiation with high-LET ions, but not γ-rays, stimulated exosome release by about 4-fold, relative to mock-irradiated controls. The exosome-enriched vesicle preparations contained pro-inflammatory damage-associated molecular patterns, including HSP70 and calreticulin. Additionally, miRNA profiling was performed for vesicular RNAs using NanoString technology. The miRNA profile was skewed toward a small number of species that have previously been shown to be involved in cancer initiation and progression, including miR-1246, miR-1290, miR-23a, and miR-205. Additionally, a set of 24 miRNAs was defined as modestly over-represented in preparations from HZE ion-irradiated versus other cells. Gene set enrichment analysis based on the over-represented miRNAs showed highly significant association with nonsmall cell lung and other cancers.
Zhentian Li, Kishore K Jella, Lahcen Jaafar, Carlos S Moreno, William S Dynan
2709 related Products with: Characterization of exosome release and extracellular vesicle-associated miRNAs for human bronchial epithelial cells irradiated with high charge and energy ions.100ul200 0.1 mg1000 1 ml25 TESTS25 4 Membranes/Box10 ug1.00 flask1,000 tests
#33608912 2021/02/20 To Up
Microglial phagocytosis of neurons in neurodegeneration, and its regulation.There is growing evidence that excessive microglial phagocytosis of neurons and synapses contributes to multiple brain pathologies. RNA-seq and genome wide association (GWAS) studies have linked multiple phagocytic genes to neurodegenerative diseases, and knock-out of phagocytic genes has been found to protect against neurodegeneration in animal models, suggesting that excessive microglial phagocytosis contributes to neurodegeneration. Here, we review recent evidence that microglial phagocytosis of live neurons and synapses causes neurodegeneration in animal models of Alzheimer's disease and other tauopathies, Parkinson's disease, frontotemporal dementias, multiple sclerosis, retinal degeneration, and neurodegeneration induced by ischaemia, infection or ageing. We also review factors regulating microglial phagocytosis of neurons, including: nucleotides, frackalkine, phosphatidylserine, calreticulin, UDP, CD47, sialylation, complement, galectin-3, Apolipoprotein E, phagocytic receptors, Siglec receptors, cytokines, microglial epigenetics and expression profile. Some of these factors may be potential treatment targets to prevent neurodegeneration mediated by excessive microglial phagocytosis of live neurons and synapses.
Claire A Butler, Alma Popescu, Emily Kitchener, David H Allendorf, Mar Puigdellívol, Guy C Brown
1427 related Products with: Microglial phagocytosis of neurons in neurodegeneration, and its regulation.96 wells300 units2 Pieces/Box1ml100 μg1 Set100 μg1 Set100 100ug1 Set
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#33593418 2021/02/16 To Up
Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity.Bariatric surgery, especially Roux-en-Y gastric bypass (RYGB), is the most effective and durable treatment option for severe obesity. The mechanisms involving adipose tissue may be important to explain the effects of surgery.
Rafael Ferraz-Bannitz, Caroline Rossi Welendorf, Priscila Oliveira Coelho, Wilson Salgado, Carla Barbosa Nonino, Rebeca A Beraldo, Maria Cristina Foss-Freitas
1290 related Products with: Bariatric surgery can acutely modulate ER-stress and inflammation on subcutaneous adipose tissue in non-diabetic patients with obesity.
#33591948 2021/02/11 To Up
Calreticulin: a potential diagnostic and therapeutic biomarker in gallbladder cancer.Recent studies suggested that calreticulin (CRT) has an important role in the progression of various types of cancer. Our previous study suggested that CRT was upregulated and acted as an oncogene in hepatocellular carcinoma. However, the role of CRT in gallbladder cancer (GBC) remains unclear. The expression level of CRT was upregulated in GBC tissues in comparison with adjacent non-tumor tissues and chronic cholecystitis tissues. Moreover, CRT expression was found to be correlated with the tumor size. Knockdown of CRT inhibited cell proliferation, induced apoptosis, arrested cell cycle and resulted in decreased resistance to gemcitabine, which was mediated by the inactivation of the PI3K/Akt pathway. Collectively, the present results suggested a potential role of CRT in GBC progression and provided novel insights into the mechanism underlying the CRT-mediated chemosensitivity in GBC cells.
Jianwen Ye, Lei Qi, Zhicheng Du, Long Yu, Kunlun Chen, Renfeng Li, Ruo Feng, Wenlong Zhai
1943 related Products with: Calreticulin: a potential diagnostic and therapeutic biomarker in gallbladder cancer.
#33585151 2021/02/03 To Up
Site-directed mutagenesis in the P-domain of calreticulin transacylase identifies Lys-207 as the active site residue.In silico-docking studies from previous work have suggested that Lys-206 and lys-207 of calreticulin (CR) play a pivotal key role in its well-established transacetylation activity. To experimentally validate this prediction, we introduced three mutations at lysine residues of P-domain of CR: K → A, (K -206, -209), (K -206, -207) and (K -207, -209) and analyzed their immunoreactivity and acetylation potential. The clones of wild-type P-domain ( ) and three mutated P-domain (, and ) were expressed in pTrcHis C vector and the recombinant , , and proteins were purified by Ni-NTA affinity chromatography. Screening of the transacylase activity (TAase) by the Glutathione S Transferase (GST) assay revealed that the TAase activity was associated with the and while and did not show any activity. The immune-reactivity to anti-lysine antibody was also retained only by the in which the Lys-207 was intact. Retention of the TAase activity and immunoreactivity of with mutations introduced at Lys-206, Lys-209, while its loss with a mutation at Lys-207 residue indicated that lysine-207 of P-domain constitutes the active site residue controlling TAase activity.
Rini Joshi, Prabhjot Singh, Naresh K Sharma, Prija Ponnan, Daman Saluja, Jasvinder K Gambhir, Diwan S Rawat, Virinder S Parmar, Bilkere S Dwarakanath, Ashok K Prasad, Hanumantharao G Raj
2531 related Products with: Site-directed mutagenesis in the P-domain of calreticulin transacylase identifies Lys-207 as the active site residue.48 samples100μg0.1mg100μg
#33580514 2021/02/12 To Up
ATAD3A stabilizes GRP78 to suppress ER stress for acquired chemoresistance in colorectal cancer.AAA domain containing 3A (ATAD3A) is a nucleus-encoded mitochondrial protein with vital function in communication between endoplasmic reticulum (ER) and mitochondria which is participated in cancer metastasis. Here we show that elevated ATAD3A expression is clinically associated with poor 5-year disease-free survival in patients with colorectal cancer (CRC), especially high-risk CRC patients who received adjuvant chemotherapy. Our results indicated ATAD3A is significantly upregulated to reduce chemotherapy-induced cancer cell death. We found that knockdown of ATAD3A leads to dysregulation in protein processing for inducing ER stress by RNA sequencing (RNA-seq). In response to chemotherapy-induced ER stress, ATAD3A interacts with elevated GRP78 protein to assist protein folding and alleviate ER stress for cancer cell survival. This reduction of ER stress leads to reduce the surface exposure of calreticulin, which is the initiator of immunogenic cell death and antitumor immunity. However, silencing of ATAD3A enhances cell death, triggers the feasibility of chemotherapy-induced ER stress for antitumor immunity, increases infiltration of T lymphocytes and delays tumor regrowth in vitro and in vivo. Clinically, CRC patients with less ATAD3A have high density of CD45 intratumoral infiltrating lymphocytes (TILs) and memory CD45RO TILs. Taken together, our results suggest that pharmacologic targeting to ATAD3A might be a potential therapeutic strategy to enhance antitumor immunity for CRC patients who received adjuvant chemotherapy.
Kevin Chih-Yang Huang, Shu-Fen Chiang, Pei-Chen Yang, Tao-Wei Ke, Tsung-Wei Chen, Chen-Yu Lin, Hsin-Yu Chang, William Tzu-Liang Chen, Kun-San Clifford Chao
2765 related Products with: ATAD3A stabilizes GRP78 to suppress ER stress for acquired chemoresistance in colorectal cancer.
#33574943 2021/01/12 To Up
Gene expression profiling of CD34(+) cells from patients with myeloproliferative neoplasms.Myeloproliferative neoplasms (MPN) are clonal disorders characterized by the increased proliferation of hematopoietic stem cell precursors and mature blood cells. Mutations of Janus kinase 2 (2), Calreticulin () and (myeloproliferative leukemia virus) are key driver mutations in MPN. However, the molecular profile of triple negative MPN has been a subject of ambiguity over the past few years. Mutations of, methylcytosine dioxygenase , polycomb group protein and histone-lysine N-methyltransferase genes have accounted for certain subsets of triple negative MPNs but the driving cause for majority of cases is still unexplored. The present study performed a microarray-based transcriptomic profile analysis of bone marrow-derived CD34(+) cells from seven MPN samples. A total of 21,448 gene signatures were obtained, which were further filtered into 472 upregulated and 202 downregulated genes. Gene ontology and protein-protein interaction (PPI) network analysis highlighted an upregulation of genes involved in cell cycle and chromatin modification in V617F negative vs. positive MPN samples. Out of the upregulated genes, seven were associated with the hematopoietic stem cell signature, while forty-seven were associated with the embryonic stem cell signature. The majority of the genes identified were under the control of and transcription factors. The PPI network indicated a strong interaction between chromatin modifiers and cell cycle genes, such as histone-lysine N-methyltransferase , SWI/SNF complex subunit , chromatin remodeling complex subunit , tubulin β () and cyclin dependent kinase . Among the upregulated epigenetic markers, there was a ~10-fold increase in expression in V617F negative samples. A significant increase in total CD34 counts in 2V617F negative vs. positive samples (P<0.05) was also observed. Overall, the present data showed a distinct pattern of expression in 2V617F negative vs. positive samples with upregulated genes involved in epigenetic modification.
Mugdha Sharma, Chandra Bhavani, Srinag Bangalore Suresh, John Paul, Lokendra Yadav, Cecil Ross, Sweta Srivastava
2996 related Products with: Gene expression profiling of CD34(+) cells from patients with myeloproliferative neoplasms.300 units1.00 flask44
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