排序方式: 共有33条查询结果,搜索用时 9 毫秒
1.
Azam Khedri Shahnaz Khaghani Alireza Kheirollah Hossein Babaahmadi-Rezaei Amir Shadboorestan Mohammad Zangooei Hajar Shokri Afra Reza Meshkani Mohammad Hossein Ghahremani 《Journal of cellular biochemistry》2019,120(6):9125-9137
Fragile histidine trail (FHIT) is a tumor suppressor in response to DNA damage which has been deleted in various tumors. However, the signaling mechanisms and interactions of FHIT with regard to apoptotic proteins including p53 and p38 in the DNA damage-induced apoptosis are not well described. In the present study, we used etoposide-induced DNA damage in MCF-7 as a model to address these crosstalks. The time course study showed that the expression of FHIT, p53, and p38MAPK started after 1 hour following etoposide treatment. FHIT overexpression led to increase p53 expression, p38 activation, and augmented apoptosis following etoposide-induced DNA damage compared to wild-type cells. However, FHIT knockdown blocked p53 expression, delayed p38 activation, and completely inhibited etoposide-induced apoptosis. Inhibition of p38 activity prevented induction of p53, FHIT, and apoptosis in this model. Thus, activation of p38 upon etoposide treatment leads to increase in FHIT and p53 expression. In p53 knockdown MCF-7, the FHIT induction was hampered but p38 activation was induced in lower doses of etoposide. In p53 knockdown cells, inhibition of p38 induced FHIT expression and apoptosis. Our data demonstrated that the exposure of MCF-7 cells to etoposide increases apoptosis through a mechanism involving the activation of the p38-FHIT-p53 pathway. Moreover, our findings suggest signaling interaction for these pathways may represent a promising therapy for breast cancer. 相似文献
2.
Ismawati Ismawati Ilhami Romus Mukhyarjon Mukhyarjon Afra Muthya 《Reports of Biochemistry & Molecular Biology》2022,10(4):633
Background:The effect of proteasome inhibitors on atherosclerosis is known to vary depending on the atherosclerosis stage. Previous studies have shown that the highest proteasome expression in atherosclerotic lesions is at the progression stage. Adhesion molecules play a role in the progression stage of atherosclerosis, but no studies have analyzed the effect of proteasome inhibitors on the expression of adhesion molecules at this stage.Methods:This experimental study aimed to analyze the effect of a proteasome inhibitor, namely bortezomib, on the vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule1 (ICAM-1) expressions in blood vessels of rat model of atherosclerosis at the progression stage. This study used 18 male Wistar rats divided into three groups, i.e. group I that is the control group given standard feed, group II induced by atherosclerosis, and group III induced by atherosclerosis and given bortezomib. Atherosclerosis induction was performed using vitamin D3 (700,000 IU/kg) orally by gastric intubation on the 1st day and atherogenic feed given for four days. Bortezomib 50 µg/kgBW/day was administered intra-peritoneally. The expression of VCAM-1 and ICAM-1 molecules was measured using immunohistochemistry and analyzed quantitatively using Adobe Photoshop software.Results:The statistical test showed differences in VCAM-1 expression between atherosclerosis + Bortezomib group and atherosclerosis group, but there were no differences in the expression of ICAM-1 and atherosclerotic lesions between the groups.Conclusion:Administration of bortezomib 50μg/kg for four days in progressive atherosclerosis model rats can inhibit VCAM-1 expression, although it does not affect ICAM-1 expression and cannot inhibit atherosclerotic lesion formation.Key Words: Atherosclerosis, Bortezomib, Proteasome, VCAM-1, ICAM-1 相似文献
3.
Anne L. Wheeler Cátia M. Teixeira Afra H. Wang Xuejian Xiong Natasa Kovacevic Jason P. Lerch Anthony R. McIntosh John Parkinson Paul W. Frankland 《PLoS computational biology》2013,9(1)
Long-term memories are thought to depend upon the coordinated activation of a broad network of cortical and subcortical brain regions. However, the distributed nature of this representation has made it challenging to define the neural elements of the memory trace, and lesion and electrophysiological approaches provide only a narrow window into what is appreciated a much more global network. Here we used a global mapping approach to identify networks of brain regions activated following recall of long-term fear memories in mice. Analysis of Fos expression across 84 brain regions allowed us to identify regions that were co-active following memory recall. These analyses revealed that the functional organization of long-term fear memories depends on memory age and is altered in mutant mice that exhibit premature forgetting. Most importantly, these analyses indicate that long-term memory recall engages a network that has a distinct thalamic-hippocampal-cortical signature. This network is concurrently integrated and segregated and therefore has small-world properties, and contains hub-like regions in the prefrontal cortex and thalamus that may play privileged roles in memory expression. 相似文献
4.
Ahammad Ishtiaque Sarker Md. Rafiul Islam Khan Akib Mahmud Islam Sohidul Hossain Mahmud 《International journal of peptide research and therapeutics》2020,26(4):1923-1938
International Journal of Peptide Research and Therapeutics - Overexpression of ERBBB family of receptors (ERBB1, ERBB2, ERBB3 and ERBB4) has been found to be hyper-activated in a number of... 相似文献
5.
6.
A hitherto unknown hydroxy acid has been isolated from Blepharis sindica seed oil has been characterized as 9-hydroxydodecanoic acid by IR, NMR and mass spectral studies. The structure of this acid was further supported by its chemical transformations. 相似文献
7.
8.
Ishtiaque Rashid Michal Hammel Aleksandr Sverzhinsky Miaw-Sheue Tsai John M. Pascal John A. Tainer Alan E. Tomkinson 《The Journal of biological chemistry》2021,297(2)
Tyrosyl DNA phosphodiesterase 1 (TDP1) and DNA Ligase IIIα (LigIIIα) are key enzymes in single-strand break (SSB) repair. TDP1 removes 3′-tyrosine residues remaining after degradation of DNA topoisomerase (TOP) 1 cleavage complexes trapped by either DNA lesions or TOP1 inhibitors. It is not known how TDP1 is linked to subsequent processing and LigIIIα-catalyzed joining of the SSB. Here we define a direct interaction between the TDP1 catalytic domain and the LigIII DNA-binding domain (DBD) regulated by conformational changes in the unstructured TDP1 N-terminal region induced by phosphorylation and/or alterations in amino acid sequence. Full-length and N-terminally truncated TDP1 are more effective at correcting SSB repair defects in TDP1 null cells compared with full-length TDP1 with amino acid substitutions of an N-terminal serine residue phosphorylated in response to DNA damage. TDP1 forms a stable complex with LigIII170–755, as well as full-length LigIIIα alone or in complex with the DNA repair scaffold protein XRCC1. Small-angle X-ray scattering and negative stain electron microscopy combined with mapping of the interacting regions identified a TDP1/LigIIIα compact dimer of heterodimers in which the two LigIII catalytic cores are positioned in the center, whereas the two TDP1 molecules are located at the edges of the core complex flanked by highly flexible regions that can interact with other repair proteins and SSBs. As TDP1and LigIIIα together repair adducts caused by TOP1 cancer chemotherapy inhibitors, the defined interaction architecture and regulation of this enzyme complex provide insights into a key repair pathway in nonmalignant and cancer cells. 相似文献
9.
Neural circuits underlying imitation learning of hand actions: an event-related fMRI study 总被引:20,自引:0,他引:20
The neural bases of imitation learning are virtually unknown. In the present study, we addressed this issue using an event-related fMRI paradigm. Musically naive participants were scanned during four events: (1) observation of guitar chords played by a guitarist, (2) a pause following model observation, (3) execution of the observed chords, and (4) rest. The results showed that the basic circuit underlying imitation learning consists of the inferior parietal lobule and the posterior part of the inferior frontal gyrus plus the adjacent premotor cortex (mirror neuron circuit). This circuit, known to be involved in action understanding, starts to be active during the observation of the guitar chords. During pause, the middle frontal gyrus (area 46) plus structures involved in motor preparation (dorsal premotor cortex, superior parietal lobule, rostral mesial areas) also become active. Given the functional properties of area 46, a model of imitation learning is proposed based on interactions between this area and the mirror neuron system. 相似文献
10.
New neurons are continuously generated in the subgranular zone of the hippocampus throughout adulthood, and there is increasing interest as to whether these new neurons become functionally integrated into memory circuits. This protocol describes the immunohistochemical procedures to visualize the recruitment of new neurons into circuits supporting spatial memory in intact mice. To label adult-generated granule cells, mice are injected with the proliferation marker 5-bromo-2'-deoxyuridine (BrdU). At different delays after BrdU treatment, mice are trained to locate a hidden platform in the Morris water maze, and spatial memory can then be tested in a probe test with the platform removed from the pool. Ninety minutes after this probe test, mice are perfused and tissue is sectioned. Immunohistochemical procedures are used to quantify BrdU-labeled cells and expression of the immediate early gene, Fos. Because Fos expression is regulated by neuronal activity, the degree of overlap between BrdU-labeled and Fos-labeled neurons provides an indication of whether adult-generated granule neurons have been incorporated into spatial memory circuits. 相似文献