Bax shuttling after rotenone treatment of neuronal primary cultures: Effects on cell death phenotypes

2009 ◽  
Vol 87 (9) ◽  
pp. 2047-2065 ◽  
Author(s):  
Martin B. Gill ◽  
J. Regino Perez-Polo
Keyword(s):  
Cell Death ◽  
Primary Cultures ◽  
Rotenone Treatment ◽  
Neuronal Primary Cultures

μ-Opiate Receptors in Neuronal Primary Cultures from Cerebral Cortex

1990 ◽  
Vol 17 (3) ◽  
pp. 177-181
Author(s):  
Peter S. Eriksson ◽  
Elisabeth Hansson ◽  
Lars Rönnbäck
Keyword(s):  
Cerebral Cortex ◽  
Primary Cultures ◽  
Opiate Receptors ◽  
Neuronal Cultures ◽  
Camp Accumulation ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Neuronal Primary Cultures ◽  
Dose Dependent ◽  
Μ Receptor

The presence of μ-opioid receptors was demonstrated as effects of receptor stimulation on PGE1-induced cAMP accumulation in neuronal-enriched primary cultures from rat cerebral cortex. Morphine was used as a μ-receptor agonist. There was a dose-dependent inhibition of the PGE1-stimulated cAMP accumulation by morphine, blocked by the μ-receptor antagonist naloxone. These findings suggest that these neuronal cultures express μ-receptors, possibly connected to adenylate cyclase via an inhibitory Gi-protein. The probable use of functional μ-receptors in neurotoxicological tests is discussed.

Mechanisms of death induced by cisplatin in proximal tubular epithelial cells: apoptosis vs. necrosis

1996 ◽  
Vol 270 (4) ◽  
pp. F700-F708 ◽  
Author(s):  
W. Lieberthal ◽  
V. Triaca ◽  
J. Levine
Keyword(s):  
Cell Death ◽  
Dna Cleavage ◽  
Primary Cultures ◽  
Cell Monolayer ◽  
Membrane Integrity ◽  
Ladder Pattern ◽  
Proximal Tubular Epithelial Cells ◽  
Proximal Tubular ◽  
High Concentrations ◽  
Induced Apoptosis

We have examined the mechanisms of cell death induced by cisplatin in primary cultures of mouse proximal tubular cells. High concentrations of cisplatin (800 microM) led to necrotic cell death over a few hours. Much lower concentrations of cisplatin (8 microM) led to apoptosis, which caused loss of the cell monolayer over several days. Necrosis was characterized by a cytosolic swelling and early loss of plasma membrane integrity. In contrast, early features of cells undergoing apoptosis included cell shrinkage and loss of attachment to the monolayers. Nuclear chromatin became condensed and fragmented in apoptosing cells. These features were absent in necrotic cells. DNA electrophoresis of cells exposed to 800 microM cisplatin yielded a "smear" pattern, due to random DNA degradation. In contrast, the DNA of apoptosing cells demonstrated a "ladder" pattern resulting from internucleosomal DNA cleavage. Antioxidants delayed cisplatin-induced apoptosis but not necrosis. Thus the mechanism of cell death induced by cisplatin is concentration dependent. Reactive oxygen species play a role in mediating apoptosis but not necrosis induced by cisplatin.

scholarly journals Comparison of Gene Expression Profile in Embryonic Mesencephalon and Neuronal Primary Cultures

PLoS ONE ◽  
2009 ◽  
Vol 4 (3) ◽  
pp. e4977 ◽  
Author(s):  
Dario Greco ◽  
Floriana Volpicelli ◽  
Antonio Di Lieto ◽  
Damiana Leo ◽  
Carla Perrone-Capano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Primary Cultures ◽  
Neuronal Primary Cultures

Poly(ADP-ribose) polymerase-1-deficient mice are protected from angiotensin II-induced cardiac hypertrophy

2006 ◽  
Vol 291 (4) ◽  
pp. H1545-H1553 ◽  
Author(s):  
Jyothish B. Pillai ◽  
Madhu Gupta ◽  
Senthilkumar B. Rajamohan ◽  
Roberto Lang ◽  
Jai Raman ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Cell Signaling ◽  
Primary Cultures ◽  
Heart Weight ◽  
Cell Protein ◽  
Sequence Of Events ◽  
Deficient Mice

Poly(ADP-ribose) polymerase-1 (PARP), a chromatin-bound enzyme, is activated by cell oxidative stress. Because oxidative stress is also considered a main component of angiotensin II-mediated cell signaling, it was postulated that PARP could be a downstream target of angiotensin II-induced signaling leading to cardiac hypertrophy. To determine a role of PARP in angiotensin II-induced hypertrophy, we infused angiotensin II into wild-type (PARP+/+) and PARP-deficient mice. Angiotensin II infusion significantly increased heart weight-to-tibia length ratio, myocyte cross-sectional area, and interstitial fibrosis in PARP+/+ but not in PARP−/− mice. To confirm these results, we analyzed the effect of angiotensin II in primary cultures of cardiomyocytes. When compared with PARP−/− cardiomyocytes, angiotensin II (1 μM) treatment significantly increased protein synthesis in PARP+/+ myocytes, as measured by 3H-leucine incorporation into total cell protein. Angiotensin II-mediated hypertrophy of myocytes was accompanied with increased poly-ADP-ribosylation of nuclear proteins and depletion of cellular NAD content. When cells were treated with cell death-inducing doses of angiotensin II (10–20 μM), robust myocyte cell death was observed in PARP+/+ but not in PARP−/− myocytes. This type of cell death was blocked by repletion of cellular NAD levels as well as by activation of the longevity factor Sir2α deacetylase, indicating that PARP induction and subsequent depletion of NAD levels are the sequence of events causing angiotensin II-mediated cardiomyocyte cell death. In conclusion, these results demonstrate that PARP is a nuclear integrator of angiotensin II-mediated cell signaling contributing to cardiac hypertrophy and suggest that this could be a novel therapeutic target for the management of heart failure.

Clinical Responses to EGFr-TKI’s characterized by drug-induced cell death in human NSCLC primary cultures

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 18184-18184
Author(s):  
R. A. Nagourney ◽  
M. Paulsen ◽  
D. Mc Connell ◽  
R. Shuman
Keyword(s):  
Cell Death ◽  
Programmed Cell Death ◽  
Clinical Response ◽  
Primary Cultures ◽  
Single Agent ◽  
Human Tumor ◽  
Egfr Mutations ◽  
Molecular Profile ◽  
Nsclc Patients ◽  
Human Nsclc

18184 Background: Small molecule inhibitors of the EGFr have proven effective in advanced NSCLC but response rates in unselected populations remain low. Certain subsets of patients appear favored including females, non-smokers and Asians. Molecular profiles suggest that gene amplification or EGFr mutations (codons 19–21) may underlie responses. Our prior observations (Proc. AACR 2002, Abs.3902) indicated that gefitinib and erlotinib induced cell-death in human tumor microspheroids isolated from surgical specimens of some NSCLC patients, suggesting programmed cell death to be an important mechanism of action for these molecules. As part of an IRB-approved clinical trial, patients whose tumors were found sensitive to the EGFr-TKI’s by laboratory analysis, received 1st line single agent oral erlotinib at 150 mg/day. Methods: Following informed consent, NSCLC patients participating in the trial provided tissue for analysis as previously described (J Clin Oncol, 2000 18: 2245–2249). Dose response curves provided LC50 values by interpolation. Modified Z-score analysis identified patients sensitive to the EGFr-TKI’s by comparison with a database of over 900 EGFr-TKI analyses. Results: Three female caucasian patients were found more sensitive to EGFr-TKI’s than cytotoxic chemotherapy (2 non- & 1 former smoker). All 3 responded to erlotinib, 2 near-CR by PET, 1 lasting 19 months, the 2nd continuing at 10 months, with a 3rd patient in continuous PR at month 6. Toxicities have been moderate. One near-CR had virtually no skin rash. The molecular profile of 1 near-CR revealed no known gain of function mutation but instead a novel mutation in the EGFr domain. Conclusions: Exposure of human NSCLC microspheroids to EGFr-TKI’s in short term culture results in cell death events associated with clinical response, suggesting that programmed cell death is an important determinant of clinical response to these agents. This is consistent with the concept of oncogene addiction, in tumors driven by EGFr upregulation. Accrual to this trial continues. Supported by the Memorial Medical Center Foundation. [Table: see text]

Graded ATP depletion can cause necrosis or apoptosis of cultured mouse proximal tubular cells

1998 ◽  
Vol 274 (2) ◽  
pp. F315-F327 ◽  
Author(s):  
Wilfred Lieberthal ◽  
Sarah A. Menza ◽  
Jerrold S. Levine
Keyword(s):  
Cell Death ◽  
Narrow Range ◽  
Apoptotic Cell ◽  
Primary Cultures ◽  
Atp Depletion ◽  
High Dose ◽  
Renal Growth ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Epidermal Growth

The mechanisms of cell death induced by ATP depletion were studied in primary cultures of mouse proximal tubular (MPT) cells. Graded ATP depletion, ranging in severity from ∼2 to 70% of control levels, was induced by incubating cells with either antimycin or 2-deoxyglucose, with varying concentrations of dextrose. We found that cells subjected to ATP depletion below ∼15% of control died uniformly of necrosis. In contrast, cells subjected to ATP depletion between ∼25 and 70% of control all died by apoptosis. The rapidity of cell death was proportional to the severity of reduction of cell ATP content and was independent of the mechanism of cell death. Renal growth factors, epidermal growth factor (EGF) and high-dose insulin, did not ameliorate apoptotic cell death induced by ATP depletion. We conclude that ATP depletion can cause either necrosis or apoptosis in MPT cells. Furthermore, we have identified a narrow range of ATP depletion (∼15 to 25% of control) representing a threshold that determines whether cells die by necrosis or apoptosis.

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