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intrinsic apoptosis pathway

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https://www.readbyqxmd.com/read/28340475/irinotecan-upregulates-fibroblast-growth-factor-receptor-3-expression-in-colorectal-cancer-cells-which-mitigates-irinotecan-induced-apoptosis
#1
Zeynep N Erdem, Stefanie Schwarz, Daniel Drev, Christine Heinzle, Andrea Reti, Petra Heffeter, Xenia Hudec, Klaus Holzmann, Bettina Grasl-Kraupp, Walter Berger, Michael Grusch, Brigitte Marian
BACKGROUND: Irinotecan (IRI) is an integral part of colorectal cancer (CRC) therapy, but response rates are unsatisfactory and resistance mechanisms are still insufficiently understood. As fibroblast growth factor receptor 3 (FGFR3) mediates essential survival signals in CRC, it is a candidate gene for causing intrinsic resistance to IRI. METHODS: We have used cell line models overexpressing FGFR3 to study the receptor's impact on IRI response. For pathway blockade, a dominant-negative receptor mutant and a small molecule kinase inhibitor were employed...
March 21, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28336431/calcium-sensing-receptor-antagonist-nps2390-attenuates-neuronal-apoptosis-though-intrinsic-pathway-following-traumatic-brain-injury-in-rats
#2
Zhaoliang Xue, Zhengfei Song, Yingfeng Wan, Kun Wang, Lianjie Mo, Yirong Wang
Traumatic brain injury (TBI) initiates a complex cascade of neurochemical and signaling changes that leads to neuronal apoptosis, which contributes to poor outcomes for patients with TBI. Previous study indicates that calcium-sensing receptor (CaSR) activation contributes to neuron death in focal cerebral ischemia-reperfusion mice, however, its role in neuronal apoptosis after TBI is not well-established. Using a controlled cortical impact model in rats, the present study was designed to determine the effect of CaSR inhibitor NPS2390 upon neuronal apoptosis after TBI...
March 20, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#3
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28320189/tempol-4-hydroxy-tempo-inhibits-anoxia-induced-progression-of-mitochondrial-dysfunction-and-associated-neurobehavioral-impairment-in-neonatal-rats
#4
Puneet K Samaiya, Gopeshwar Narayan, Ashok Kumar, Sairam Krishnamurthy
BACKGROUND: Anoxia leads to a robust generation of reactive oxygen species/nitrogen species which can result in mitochondrial dysfunction and associated cell death in the cerebral cortex of neonates. AIM: The present study investigated the pharmacological role of tempol in the treatment of rat neonatal cortical mitochondrial dysfunction induced insult progression (day-1 to day-7) and associated neurobehavioral alterations post-anoxia. METHODS: Rat pups of 30h age or postnatal day 2 (PND2) were randomly divided into 5 groups (n=5 per group): (1) Control; (2) Anoxia; (3) Anoxia+Tempol 75mg/kg; (4) Anoxia+Tempol 150mg/kg; and (5) Anoxia+Tempol 300mg/kg, and subjected to two episode of anoxia (10min each) at 24h of time interval in an enclosed chamber supplied with 100% N2...
April 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28319728/modulation-of-host-cell-apoptotic-pathways-by-intracellular-pathogens
#5
REVIEW
Anja Friedrich, Julian Pechstein, Christian Berens, Anja Lührmann
Nearly all steps of the host cell apoptotic cascade can be subverted by intracellular microorganisms. Some pathogens modulate early steps and interfere with sensing of extracellular signals, cellular stress or signal transduction; others target Bcl-2 proteins, caspases, or inhibitor of apoptosis proteins (IAPs). In many cases the exact molecular mechanisms leading to interference with the host cell apoptotic cascade are still unknown. However, there are some examples where bacterial factors that modulate host cell death have been identified...
March 17, 2017: Current Opinion in Microbiology
https://www.readbyqxmd.com/read/28317867/double-knockout-of-bax-and-bak-from-kidney-proximal-tubules-reduces-unilateral-urethral-obstruction-associated-apoptosis-and-renal-interstitial-fibrosis
#6
Shuqin Mei, Lin Li, Qingqing Wei, Jielu Hao, Yunchao Su, Changlin Mei, Zheng Dong
Interstitial fibrosis, a common pathological feature of chronic kidney diseases, is often associated with apoptosis in renal tissues. To determine the associated apoptotic pathway and its role in renal interstitial fibrosis, we established a mouse model in which Bax and Bak, two critical genes in the intrinsic pathway of apoptosis, were deleted specifically from kidney proximal tubules and used this model to examine renal apoptosis and interstitial fibrosis following unilateral urethral obstruction (UUO). It was shown that double knockout of Bax and Bak from proximal tubules attenuated renal tubular cell apoptosis and suppressed renal interstitial fibrosis in UUO...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315432/splicing-factors-of-sr-and-hnrnp-families-as-regulators-of-apoptosis-in-cancer
#7
Hanna Kędzierska, Agnieszka Piekiełko-Witkowska
SR and hnRNP proteins were initially discovered as regulators of alternative splicing: the process of controlled removal of introns and selective joining of exons through which multiple transcripts and, subsequently, proteins can be expressed from a single gene. Alternative splicing affects genes involved in all crucial cellular processes, including apoptosis. During cancerogenesis impaired apoptotic control facilitates survival of cells bearing molecular aberrations, contributing to their unrestricted proliferation and chemoresistance...
March 14, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28315370/control-of-mitochondrial-physiology-and-cell-death-by-the-bcl-2-family-proteins-bax-and-bok
#8
Beatrice D'Orsi, Julia Mateyka, Jochen H M Prehn
Neuronal cell death is often triggered by events that involve intracellular increases in Ca(2+). Under resting conditions, the intracellular Ca(2+) concentration is tightly controlled by a number of extrusion and sequestering mechanisms involving the plasma membrane, mitochondria, and ER. These mechanisms act to prevent a disruption of neuronal ion homeostasis. As these processes require ATP, excessive Ca(2+) overloading may cause energy depletion, mitochondrial dysfunction, and may eventually lead to Ca(2+)-dependent cell death...
March 14, 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28301569/meiotic-failure-in-cyclin-a1-deficient-mouse-spermatocytes-triggers-apoptosis-through-intrinsic-and-extrinsic-signaling-pathways-and-14-3-3-proteins
#9
Sunil K Panigrahi, Marcia Manterola, Debra J Wolgemuth
Cyclin A1 (Ccna1), a member of the mammalian A type cyclins, is most abundantly expressed in spermatocytes and is essential for spermatogenesis in the mouse. Ccna1- deficient spermatocytes arrest at late meiotic prophase and undergo apoptosis. To further delineate the mechanisms and key factors involved in this process, we have examined changes in expression of genes involved in both intrinsic and extrinsic signaling pathways that trigger apoptosis in the mutant spermatocytes. Our results show that both pathways are involved, and that the factors involved in the intrinsic pathway were expressed earlier than those involved in the extrinsic pathway...
2017: PloS One
https://www.readbyqxmd.com/read/28301214/novel-glycopyrrolidine-compounds-inhibit-human-cancer-cell-proliferation-and-induce-apoptotic-mode-of-cell-death
#10
Hemadev Bhoopalan, Shilpa Tentu, Prasana R, Purushothaman S, Akkanapally Venu, Ragavachary Raghunathan, Suresh Babu Pakala, Suresh Kumar Rayala, Ganesh Venkatraman
Spirocyclic compounds, present in a number of bioactive natural alkaloids, are cyclic systems containing one carbon atom common to two rings. A highly regioselective glycopyrrolidine compound library was synthesized using 1,3-dipolar cycloaddition method, and its efficacy was tested on cell lines representing most commonly occurring cancers and the molecular mechanism of cell death deciphered. Results showed that among the 16 compounds screened, RPRR210 showed the most potent anticancer activity and induced cell cycle arrest, inhibited migration, caused cell death by inducing apoptosis through the intrinsic pathway, and were nontoxic to normal cells...
March 16, 2017: Cancer Investigation
https://www.readbyqxmd.com/read/28297832/-effects-of-high-intensity-focused-ultrasound-on-apoptosis-associated-gene-expression-in-xenografts-with-human-pancreatic-cancer
#11
L L Hong, Z Guo, W G Xing, H P Yu, C F Liu, X L Yang, H L Wang
Objective: To identify the expression of apoptosis-associated genes of high- intensity focused ultrasound(HIFU) in xenograft with human pancreatic cancer. Methods: Mice implated with human pancreatic cancer cells (YY-1) were divided into HIFU group or control group. Tumor cell apoptosis was verified by TUNEL. The expression of the apoptosis-associated genes was analyzed by Agilent Human Gene Expression. Selected genes was validated by quantitative real-time PCR(RT-PCR)and Western blot. Results: The rate of tumor cell apoptosis in HIFU group was higher than that of control group at 7, 14 days after HIFU treatment ((63...
March 7, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28296810/activation-associated-accelerated-apoptosis-of-memory-b-cells-in-critically-ill-patients-with-sepsis
#12
Manu Shankar-Hari, David Fear, Paul Lavender, Tracey Mare, Richard Beale, Chad Swanson, Mervyn Singer, Jo Spencer
OBJECTIVE: Sepsis is life-threatening organ dysfunction due to dysregulated host responses to infection. Current knowledge of human B-cell alterations in sepsis is sparse. We tested the hypothesis that B-cell loss in sepsis involves distinct subpopulations of B cells and investigated mechanisms of B-cell depletion. DESIGN: Prospective cohort study. SETTING: Critical care units. PATIENTS: Adult sepsis patients without any documented immune comorbidity...
March 14, 2017: Critical Care Medicine
https://www.readbyqxmd.com/read/28280360/arenobufagin-activates-p53-to-trigger-esophageal-squamous-cell-carcinoma-cell-apoptosis-in-vitro-and-in-vivo
#13
Junhong Lv, Shaohuan Lin, Panli Peng, Changqing Cai, Jianming Deng, Mingzhi Wang, Xuejun Li, Rongsheng Lin, Yu Lin, Ailing Fang, Qiling Li
Esophageal squamous cell carcinoma (ESCC) is often diagnosed at late incurable stage and lacks effective treatment strategy. Bufadienolides are cardiotonic steroids isolated from the skin and parotid venom glands of the toad Bufo bufo gargarizans Cantor with novel anticancer activity. However, there is little information about the effects and action mechanisms of bufadienolides on ESCC cells. In this study, the in vitro and in vivo anti-ESCC activities of bufadienolides, including bufalin (Bu) and arenobufagin (ArBu), were examined and the underlying molecular mechanisms were elucidated...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28273930/peptide-au-clusters-induced-tumor-cells-apoptosis-via-targeting-glutathione-peroxidase-1-the-molecular-dynamics-assisted-experimental-studies
#14
Meiqing Liu, Liang Gao, Lina Zhao, Jian He, Qing Yuan, Peng Zhang, Yawei Zhao, Xueyun Gao
The original motivation of the article is to give a systematic investigation on the protocol of combining computer simulation and accurate synthesis of serial peptide protected gold clusters for potent tumor targeting therapy. Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant selenoenzyme that regulates cellular redox level, thus becomes a potential target in cancer treatment. We firstly utilize molecular dynamic (MD) simulation to rationally design and screen serial peptide-Au cluster compounds with special peptide sequences and precise gold atoms, which can recognize and bind specific domain of GPx-1 with high affinity...
December 2017: Scientific Reports
https://www.readbyqxmd.com/read/28272306/akt2-blocks-nucleus-translocation-of-apoptosis-inducing-factor-aif-and-endonuclease-g-endog-while-promoting-caspase-activation-during-cardiac-ischemia
#15
Shuai Yang, Xinmei Zhao, Hui Xu, Fan Chen, Yitao Xu, Zhe Li, Daniel Sanchis, Liang Jin, Yubin Zhang, Junmei Ye
The AKT (protein kinase B, PKB) family has been shown to participate in diverse cellular processes, including apoptosis. Previous studies demonstrated that protein kinase B2 (AKT2(-/-)) mice heart was sensitized to apoptosis in response to ischemic injury. However, little is known about the mechanism and apoptotic signaling pathway. Here, we show that AKT2 inhibition does not affect the development of cardiomyocytes but increases cell death during cardiomyocyte ischemia. Caspase-dependent apoptosis of both the extrinsic and intrinsic pathway was inactivated in cardiomyocytes with AKT2 inhibition during ischemia, while significant mitochondrial disruption was observed as well as intracytosolic translocation of cytochrome C (Cyto C) together with apoptosis-inducing factor (AIF) and endonuclease G (EndoG), both of which are proven to conduct DNA degradation in a range of cell death stimuli...
March 6, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28267609/the-culicoides-sonorensis-inhibitor-of-apoptosis-1-protein-protects-mammalian-cells-from-apoptosis-induced-by-infection-with-african-horse-sickness-virus-and-bluetongue-virus
#16
Elaine Vermaak, Francois F Maree, Jacques Theron
African horse sickness virus (AHSV) and bluetongue virus (BTV) are arboviruses of the genus Orbivirus that are transmitted to their vertebrate hosts by Culicoides biting midges. These orbiviruses exhibit lytic infection (apoptosis) in mammalian cells, but cause persistent infection with no cytopathic effects in Culicoides sonorensis cells. Although regulation of apoptosis could thus be integral for establishing persistent virus infection in midge cells, nothing is known about the presence and function of apoptosis pathways in Culicoides midges and their derived cell lines...
March 4, 2017: Virus Research
https://www.readbyqxmd.com/read/28263848/phaleria-macrocarpa-boerl-fruit-induce-g0-g1-and-g2-m-cell-cycle-arrest-and-apoptosis-through-mitochondria-mediated-pathway-in-mda-mb-231-human-breast-cancer-cell
#17
Nowroji Kavitha, Chern Ein Oon, Yeng Chen, Jagat R Kanwar, Sreenivasan Sasidharan
ETHNOPHARMACOLOGICAL RELEVANCE: Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. AIM OF THE STUDY: The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death...
March 2, 2017: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/28260803/reversal-of-paclitaxel-resistance-in-human-ovarian-cancer-cells-with-redox-responsive-micelles-consisting-of-%C3%AE-tocopheryl-succinate-based-polyphosphoester-copolymers
#18
Feng-Qian Chen, Jin-Ming Zhang, Xie-Fan Fang, Hua Yu, Yu-Ling Liu, Hui Li, Yi-Tao Wang, Mei-Wan Chen
P-glycoprotein (P-gp)-mediated multidrug resistance (MDR) is a major obstacle in achieving the therapeutic benefits of paclitaxel (PTX) in the treatment of human ovarian carcinoma. This study is aimed to develop an efficient PTX drug delivery approach to overcome MDR. Redox-responsive micelles consisting of amphiphilic polymers containing disulfide linkages, ie, poly (phosphate ester)-SS-D-α-tocopheryl succinate (POPEA-SS-TOS, PSST) were prepared. PTX-loaded PSST micelles (PTX/PSST-M) designed to display synergistic functions, including reversible inhibition of P-gp, intracellular redox-sensitive release and potent anticancer activities...
March 6, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28260216/near-complete-backbone-resonance-assignments-of-acid-denatured-human-cytochrome-c-in-dimethylsulfoxide-a-prelude-to-studying-interactions-with-phospholipids
#19
Andreas Ioannis Karsisiotis, Oliver M Deacon, Colin Macdonald, Tharin M A Blumenschein, Geoffrey R Moore, Jonathan A R Worrall
Human cytochrome c plays a central role in the mitochondrial electron transfer chain and in the intrinsic apoptosis pathway. Through the interaction with the phospholipid cardiolipin, cytochrome c triggers release of pro-apoptotic factors, including itself, from the mitochondrion into the cytosol of cells undergoing apoptosis. The cytochrome c/cardiolipin complex has been extensively studied through various spectroscopies, most recently with high-field solution and solid-state NMR spectroscopies, but there is no agreement between the various studies on key structural features of cytochrome c in its complex with cardiolipin...
March 4, 2017: Biomolecular NMR Assignments
https://www.readbyqxmd.com/read/28259974/3-hydroxyterphenyllin-a-natural-fungal-metabolite-induces-apoptosis-and-s-phase-arrest-in-human-ovarian-carcinoma-cells
#20
Yaomin Wang, Casey Compton, Gary O Rankin, Stephen J Cutler, Yon Rojanasakul, Youying Tu, Yi Charlie Chen
In the present study, we evaluated 3-Hydroxyter-phenyllin (3-HT) as a potential anticancer agent using the human ovarian cancer cells A2780/CP70 and OVCAR-3, and normal human epithelial ovarian cells IOSE-364 as an in vitro model. 3-HT suppressed proliferation and caused cytotoxicity against A2780/CP70 and OVCAR-3 cells, while it exhibited lower cytotoxicity in IOSE-364 cells. Subsequently, we found that 3-HT induced S phase arrest and apoptosis in a dose-independent manner. Further investigation revealed that S phase arrest was related with DNA damage which mediated the ATM/p53/Chk2 pathway...
March 2, 2017: International Journal of Oncology
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