共查询到20条相似文献，搜索用时 21 毫秒
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Neeta Singh 《Indian journal of clinical biochemistry : IJCB》2007,22(2):6-16
Apoptosis a physiological mechanism that eliminates excessive, damaged or unwanted cells, is a highly regulated pathway important
for maintaining homeostasis in multicellular organisms. It can be initiated through various signals via the extrinsic pathway
which involves death receptors, or via the intrinsic pathway which is initiated by intracellular damage and involves the mitochondria
and release of cytochrome c from it to further activate caspases. The Bcl-2 family of proteins is situated upstream to the
irreversible damage of cellular constituents and is an important checkpoint in the fate of a cell. The pro-apoptotic members,
BH3 only members include BID, BAD and BIM. They directly or indirectly activate multidomain BAX/BAK that constitute the requisite
gateway to the intrinsic pathway which operates at the mitochondrial surface and endoplasmic reticulum. In contrast, antiapoptotic
members such as Bcl-2, Bcl-XL bind and sequester activation. Downstream of mitochondria, the apoptosome involvement is seen
to generate caspase activity. Post mitochondria regulation involves IAPs, and their inhibitors. The pathogenesis of several
diseases such as cancer, neurodegenerative disorders, autoimmune disorders, heart disease, infectious diseases including AIDS
is closely related to aberrant apoptosis. Consequently interest has emerged in employing various the rapeutic approaches such
as gene therapy, antisense therapy, recombinant biologicals, organic and combinatorial chemistry, to specifically target apoptosis
signaling pathways such as death receptors FAS/TRAIL, Bcl-2, p53, IAPs, SMAC and caspases, etc. and are now advancing from
preclinical to clinical phase. 相似文献
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Chun Ruan Xinxing Ouyang Hongzhi Liu Song Li Jingsi Jin Weiyi Tang Yu Xia Bing Su 《国家科学评论(英文版)》2019,6(6):1149
The mammalian target of rapamycin (mTOR) is an evolutionarily conserved Ser/Thr protein kinase with essential cellular function via processing various extracellular and intracellular inputs. Two distinct multi-protein mTOR complexes (mTORC), mTORC1 and mTORC2, have been identified and well characterized in eukaryotic cells from yeast to human. Sin1, which stands for Sty1/Spc1-interacting protein1, also known as mitogen-activated protein kinase (MAPK) associated protein (MAPKAP)1, is an evolutionarily conserved adaptor protein. Mammalian Sin1 interacts with many cellular proteins, but it has been widely studied as an essential component of mTORC2, and it is crucial not only for the assembly of mTORC2 but also for the regulation of its substrate specificity. In this review, we summarize our current knowledge of the structure and functions of Sin1, focusing specifically on its protein interaction network and its roles in the mTOR pathway that could account for various cellular functions of mTOR in growth, metabolism, immunity and cancer. 相似文献
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BackgroundOral cancer is one of the common malignant tumors of the head and neck. However, current treatments have numerous side effects, and drugs from natural sources may have better therapeutic potential. This research investigated the induction of apoptosis by α-hederin (α-HN), a constituent of Pulsatilla chinensis (Bunge) Regel, in the oral cancer cell line SCC-25 and its underlying mechanism.ResultsSCC-25 cells were treated with 50, 100, and 200 μmol/L α-HN. Cell proliferation; extent of apoptosis; activities of caspases-3, 8, and 9; and the expression of Bcl-2, Bax, phosphorylated (p)-phosphoinositide 3-kinase (PI3K), p-Akt, and p-mammalian target of rapamycin (mTOR) proteins were determined using the 3-(4,5)-2-thiazole-(2,5)-diphenyl tetrazolium bromide, flow cytometry, caspase activity detection kits, and western blot assays, respectively. The results showed that the proliferation of SCC-25 cells in the α-HN-treated groups decreased significantly, and the inhibitory effect was time and concentration dependent. Compared with cells in the control group, the extent of apoptosis increased significantly, caspase-3 and -9 activities were significantly enhanced, and the Bcl-2 level was lowered and the Bax level was elevated significantly in SCC-25 cells treated with α-HN for 48 h (P < 0.05). The expression of p-PI3K, p-Akt, and p-mTOR was also significantly lower in SCC-25 cells treated with α-HN than that in the control group (P < 0.05).ConclusionThese results indicate that α-HN can inhibit proliferation and induce apoptosis of SCC-25 cells and may exert these effects by inhibiting the PI3K/Akt/mTOR signaling pathway.How to cite: Wang H, Wu B, Wang H. Alpha-hederin induces the apoptosis of oral cancer SCC-25 cells by regulating PI3K/Akt/mTOR signaling pathway. Electron J Biotechnol 2019;38. https://doi.org/10.1016/j.ejbt.2018.12.005 相似文献
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宫颈鳞状上皮癌变过程中细胞周期调节通路p14^ARF-MDM2-p53作用的研究 总被引：2，自引：0，他引：2
目的 探讨细胞周期调节p14ARF-MDM2-p53通路在宫颈上皮癌变过程中的作用.方法 采用免疫组化SP法检测18例正常宫颈上皮、48例宫颈上皮内瘤变(CIN)和23例宫颈鳞状细胞癌组织p14ARF、MDM2及p53蛋白的表达.结果 p14ARF蛋白表达阳性率在正常宫颈上皮、CIN和宫颈鳞癌组分别为28%、42%和78%,宫颈鳞癌组表达较正常上皮和CIN组升高(P＜0.05);MDM2蛋白表达阳性率在正常宫颈上皮、CIN和宫颈鳞癌组分别为0%、23%和43%,CIN和宫颈鳞癌组较正常宫颈上皮表达升高(P＜0.05);p53蛋白表达阳性率在正常宫颈上皮、CIN和宫颈鳞癌组分别为6%、31%和39%,CIN及宫颈鳞癌组表达水平较正常宫颈上皮升高(P＜0.05);统计分析未发现三种蛋白的表达存在显著相关性.结论 p14ARF-MDM2-p53细胞周期调节通路与宫颈癌发生发展有关并有望用于CIN及宫颈癌的诊断. 相似文献
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Anmol Goyal Rajendra Prasad Parul Goel Amit Pal Suvarna Prasad Isha Rani 《Indian journal of clinical biochemistry : IJCB》2021,36(4):387
Coronavirus disease 2019 (Covid-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a pandemic disease which has affected more than 6.2 million people globally, with numbers mounting considerably daily. However, till date, no specific treatment modalities are available for Covid-19 and also not much information is known about this disease. Recent studies have revealed that SARS-CoV-2 infection is associated with the generation of thrombosis and coagulopathy. Fundamentally, it has been believed that a diverse array of signalling pathways might be responsible for the activation of coagulation cascade during SARS-CoV-2 infection. Henceforth, a detailed understanding of these probable underlying molecular mechanistic pathways causing thrombosis in Covid-19 disease deserves an urgent exploration. Therefore, in this review, the hypothetical crosstalk between distinct signalling pathways including apoptosis, inflammation, hypoxia and angiogenesis attributable for the commencement of thrombotic events during SARS-CoV-2 infection has been addressed which might further unravel promising therapeutic targets in Covid-19 disease. 相似文献
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Rebecca Soffe Sara Baratchi Shi-Yang Tang Arnan Mitchell Peter McIntyre Khashayar Khoshmanesh 《Biomicrofluidics》2016,10(2)
Microfluidic platforms enable a variety of physical or chemical stimulation of single or multiple cells to be examined and monitored in real-time. To date, intracellular calcium signalling research is, however, predominantly focused on observing the response of cells to a single mode of stimulation; consequently, the sensitising/desensitising of cell responses under concurrent stimuli is not well studied. In this paper, we provide an extended Discontinuous Dielectrophoresis procedure to investigate the sensitising of chemical stimulation, over an extensive range of shear stress, up to 63 dyn/cm2, which encompasses shear stresses experienced in the arterial and venus systems (10 to 60 dyn/cm2). Furthermore, the TRPV4-selective agonist GSK1016790A, a form of chemical stimulation, did not influence the ability of the cells'' to remain immobilised under high levels of shear stress; thus, enabling us to investigate shear stress stimulation on agonism. Our experiments revealed that shear stress sensitises GSK1016790A-evoked intracellular calcium signalling of cells in a shear-stimulus dependent manner, as observed through a reduction in the cellular response time and an increase in the pharmacological efficacy. Consequently, suggesting that the role of TRPV4 may be underestimated in endothelial cells—which experience high levels of shear stress. This study highlights the importance of conducting studies at high levels of shear stress. Additionally, our approach will be valuable for examining the effect of high levels of shear on different cell types under different conditions, as presented here for agonist activation. 相似文献
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Binita Goswami Pankaj Mittal Nikhil Gupta 《Indian journal of clinical biochemistry : IJCB》2013,28(1):90-94
Inflammatory pathways have garnered considerable interest in the recent past as an important mediator of the molecular mechanisms leading to carcinogenesis. The present study was conducted to evaluate the correlation of levels of IL-6 with tumor burden and receptor status in patients of locally advanced carcinoma breast. This prospective study was conducted by the collaborative efforts of the departments of Surgery and Biochemistry, Maulana Azad Medical College and associated Lok Nayak Hospital and GB Pant Hospitals, New Delhi. The study population comprised of 30 cases of locally advanced breast carcinoma recruited from the surgical outpatient department. The various parameters that were evaluated include detailed clinico-pathological profile and IL-6 levels. Tissue specimens received after surgeries were examined for the various characteristics indicative of tumor prognosis. Majority of the patients was in the age group of 41–50 years and was postmenopausal. The serum level of IL-6 increased as the disease progressed from T3N1M0 to T4dN2M0 (41.4 ± 31.9 vs. 164.0 ± 31.1 pg/ml respectively). There was significant correlation of IL-6 levels with lymph node involvement, tumor grade, mitotic index and adipose tissue invasion. Emerging molecular markers are being investigated for breast cancer prognosis assessment and prediction of response to chemotherapy including selection of best possible treatment modality. Our study showed that there is progressive increase in IL-6 levels as the stage of disease progresses. 相似文献
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Chunzhao Zhao Wei Jiang Omar Zayed Xin Liu Kai Tang Wenfeng Nie Yali Li Shaojun Xie Yuan Li Tiandan Long Linlin Liu Yingfang Zhu Yang Zhao Jian-Kang Zhu 《国家科学评论(英文版)》2021,8(1)
Salt stress is a major environmental factor limiting plant growth and productivity. We recently discovered an important new salt tolerance pathway, where the cell wall leucine-rich repeat extensins LRX3/4/5, the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23 and receptor-like kinase FERONIA (FER) function as a module to simultaneously regulate plant growth and salt stress tolerance. However, the intracellular signaling pathways that are regulated by the extracellular LRX3/4/5-RALF22/23-FER module to coordinate growth, cell wall integrity and salt stress responses are still unknown. Here, we report that the LRX3/4/5-RALF22/23-FER module negatively regulates the levels of jasmonic acid (JA), salicylic acid (SA) and abscisic acid (ABA). Blocking JA pathway rescues the dwarf phenotype of the lrx345 and fer-4 mutants, while disruption of ABA biosynthesis suppresses the salt-hypersensitivity of these mutants. Many salt stress-responsive genes display abnormal expression patterns in the lrx345 and fer-4 mutants, as well as in the wild type plants treated with epigallocatechin gallate (EGCG), an inhibitor of pectin methylesterases, suggesting cell wall integrity as a critical factor that determines the expression pattern of stress-responsive genes. Production of reactive oxygen species (ROS) is constitutively increased in the lrx345 and fer-4 mutants, and inhibition of ROS accumulation suppresses the salt-hypersensitivity of these mutants. Together, our work provides strong evidence that the LRX3/4/5-RALF22/23-FER module controls plant growth and salt stress responses by regulating hormonal homeostasis and ROS accumulation. 相似文献
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PTEN（10号染色体缺失的磷酸酶及张力蛋白同源物）作为一个重要的抑癌蛋白,其生物学功能主要体现在调节与细胞生长、增殖、分化、迁移和凋亡有关的信号通路上。在细胞中,PTEN 功能受到H2O2的氧化调节。 相似文献
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Nitric oxide (NO) a free radical having both cytoprotective as well as tumor promoting agent is formed from l-arginine by converting it to l-citrulline via nitric oxide synthase enzymes. The reaction product of nitric oxide with superoxide generates potent oxidizing
agent, peroxynitrite which is the main mediator of tissue and cellular injury. Peroxynitrite is reactive towards many biomolecules
which includes amino acids, nucleic acid bases; metal containing compounds, etc. NO metabolites may play a key role in mediating
many of the genotoxic/carcinogenic effects as DNA damage, protein or lipid modification, etc. The basic reactions of nitric
oxide can be divided as direct effect of the radical where it alone plays a role in either damaging or protecting the cell
milieu and an indirect effect in which the byproducts of nitric oxide formed by convergence of two independent radical generating
pathways play the role in biological reactions which mainly involve oxidative and nitrosative stress. Nitric oxide is also
capable of directly interacting with mitochondria through inhibition of respiration or by permeability transition. Reaction
of nitric oxide with metal ions include its direct interaction with the metals or with oxo complexes thereby reducing them
to lower valent state. Excessive production of nitric oxide can be studied by inhibiting the synthetic pathway of nitric oxide
using both selective or specific nitric oxide synthase inhibitor or non-selective nitric oxide synthase inhibitor with respect
to isoforms of nitric oxide. 相似文献
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BackgroundJatropha curcas is a wide-spreading latex-rich biodiesel plant with high oil content in seeds that have always been under intense studies. However, studies are lacking on the latex component that is considered rich in proteins with potentially important physiological functions and secondary metabolites that are a promising source for new drugs. The proteomic analysis, which would be the first step to study these substances, was hampered by the presence of interfering components. Phenol extraction and Trichloroacetic acid (TCA)/acetone extraction, two major plant proteomic isolation methods, were used and compared in this study.ResultsWe identified 459 proteins from the J. curcas latex proteome using the combination of the two extraction techniques. Although more number of latex proteins were identified by the phenol extraction (401 proteins vs. 123 proteins by the TCA/acetone extraction), only 65 proteins were commonly isolated by both methods. Analysis of the biochemical properties revealed that relatively more number of lower isoelectric point (pI) proteins were isolated by the TCA/acetone method (pI mode: 4.79, 6.51 for phenol). Moreover, GO, COG, and KEGG analyses showed that certain classes/categories/pathways annotated more number of proteins than others, and most of them had proportionally comparable protein counts by both the methods, however, with exemplified exceptions.ConclusionsA large number of proteins were found and exclusively identified by either method, indicating that a better proteome coverage of plant samples in a similar context needs the combined use of multiple isolation methods. In addition, the core biological function of the latex may be uncovered by certain GO, COG, and KEGG classes/categories/pathways that annotate more proteins. 相似文献
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《Research Policy》2023,52(9):104866
Cellular agriculture and its products, such as cultured meat, are suggested to have the potential to advance the sustainability of current food systems. Instead of engaging in current debates concerning the anticipated benefits and challenges of cellular agriculture, it is more useful to identify potential pathways leading to food system transitions. Our study aims to compare Finnish and German political stakeholders' (n = 25) perceptions concerning cultured meat and to analyse its potential transition pathways utilising the multi-level perspective (MLP). Data were collected via semi-structured theme interviews in early 2020. Results show that the participants acknowledge that landscape-level pressures, such as climate change or finite resources, are challenging current food systems. The food regime's position is perceived as somewhat uncertain. The current practices of livestock agriculture, strong food traditions and multiple interest groups' aspirations are anticipated to both hinder and advance a transition to cellular agriculture. On the niche innovation level, cultured meat was perceived as a promising yet technocratic solution. Cultured meat may be an option for continued meat consumption without feelings of guilt but with preconditions such as guaranteed safety, affordable prices and an authentic meat taste similar or better compared with conventionally produced meat. Our article concludes with three potential transition pathways for cellular agriculture. The “technocratic stagnation” pathway is characterised by perceived threats and stakeholder unwillingness to accept cultured meat. The “promising circumstances” pathway is emphasised by positive societal conditions for cultured meat development and stakeholders' incremental adaptation to it as an additional food product on the market. The “rapid advancement” pathway is characterised by technological breakthroughs and high acceptance of cultured meat, which could lead to radical changes in the current food system. 相似文献
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Ajay Kumar Khanna Sujit Yadav Z. Ali N. C. Arya Anuradha Khanna 《Indian journal of clinical biochemistry : IJCB》1996,11(1):52-55
Serum Adenosine Deaminase (ADA) activity was studied in 20 control cases and 32 patients with carcinoma breast. In control group the ADA activity ranged from 13–94 IU/L with a mean of 43.75±21.55 IU/L while in patients of carcinoma breast it was 16–95 IU/L with a mean of 47.46±22.54 IU/L, but these values were not statistically different. The ADA activity was also compared with other parameters in patients of carcinoma breast but the difference was not statistically significant in the various parameters like duration of disease, menopausal status, tumor size, hemoglobin level, total leucocyte count, absolute lymphocyte count, total serum proteins, serum albumin, histological grade of tumor and lymphocytic infiltration. The only significant difference in ADA activity was when N1 status of lymph node was compared with N2 status of lymph node. 相似文献