Cell Suicide in Health and Disease

Duke, Richard C.; Ojcius, David M.; Young, John Ding‐E

doi:10.1038/scientificamerican1296-80

Cited by 167 publications

(114 citation statements)

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“…As well as having a role in controlling cell number during early development, apoptosis is important for the removal of infected or genetically altered cells (Duke et al, 1996). Defects in the apoptotic mechanism are often found in neoplastic growth (Duke et al 1996;Green and Martin, 1995;Tompson, 1995), which is also the case in colorectal cancer (Evertsson et al, 1999;Gryfe et al, 1997;Tsujitani et al, 1996). Development of colorectal cancer proceeds through a series of genetic alterations that result in the activation of oncogenes and loss of tumor suppressor genes (Gryfe et al 1997;Rafter and Glinghammar, 1998;Ilyas et al, 1999).…”

Section: Discussionmentioning

confidence: 99%

Caspase-3 Activity as a Prognostic Factor in Colorectal Carcinoma

Jonges

Nagelkerke²,

Ensink

et al. 2001

Laboratory Investigation

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SUMMARY:Several techniques to determine apoptotic frequencies in tumors have been described. In this study, we report that biochemical detection of enzymatic caspase-3 activity is a simple and quantitative technique to measure apoptosis in colorectal tumor cells. The relevance of the level of apoptosis in colorectal cancer for the clinical course remains unclear. Therefore, we studied the correlation between caspase-3 activity and prognosis of the disease in relation to different factors known to be involved in apoptosis induction. High caspase-3 activity significantly correlated with a higher risk of recurrence and was preferentially found in tumors of the right side of the colon. No correlation was detected between high caspase-3 activity and altered protein expression of p53, ␤-catenin, or proteins of mismatched repair genes. This indicates that high caspase-3 activity has no evident correlation with the genetic Wnt-signaling or the mismatch repair mutational pathways. The caspase-3 activity significantly correlated with CD57 ϩ tumor infiltrating cells. Therefore, high caspase-3 activity in right-sided tumors might be induced by a specific lymphocytic reaction. (Lab Invest 2001, 81:681-688).A poptosis is an essential biologic process. As well as having a role in controlling cell number during early development, apoptosis is important for the removal of infected or genetically altered cells (Duke et al, 1996). Defects in the apoptotic mechanism are often found in neoplastic growth (Duke et al 1996;Green and Martin, 1995;Tompson, 1995), which is also the case in colorectal cancer (Evertsson et al, 1999;Gryfe et al, 1997;Tsujitani et al, 1996). Development of colorectal cancer proceeds through a series of genetic alterations that result in the activation of oncogenes and loss of tumor suppressor genes (Gryfe et al 1997;Rafter and Glinghammar, 1998;Ilyas et al, 1999). Mutations in genes known to be involved in cell cycle regulation, such as APC, p53, ␤-catenin, deleted in colorectal cancer (DCC), and K-ras, have been reported in colorectal cancer (reviewed in Gryfe et al, 1997). Furthermore, mutated genes involved in DNA mismatch repair can contribute to tumor growth. Alterations in these mismatch repair genes will lead to a microsatellite instability phenotype (MSI) (reviewed in Lothe, 1997). During tumorigenesis one of the target genes that is preferentially inactivated due to MSI is transforming growth factor ␤ receptor II (TGF␤RII) (Markowitz et al, 1995;Akiyama et al, 1996). Inactivation of TGF␤RII on cells down-regulates the suppressive function of TGF␤ on cell proliferation and in that way also results in disturbance of growth control (DeVisser and Kast, 1999). Most of the hereditary nonpolyposis colorectal tumors (HNPCC) exhibit MSI, whereas in sporadic colorectal cancers only 3% to 10% show this phenotype. This low rate of MSI in sporadic colorectal cancers seems to be caused by somatic inactivation of hMLH1 (Lothe, 1997).As well as the occurrence of apoptosis in cells caused by intrinsic factors, apopto...

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Section: Discussionmentioning

confidence: 99%

Caspase-3 Activity as a Prognostic Factor in Colorectal Carcinoma

Jonges

Nagelkerke²,

Ensink

et al. 2001

Laboratory Investigation

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“…In hematopoietic cells, it is thought to occur normally during maturation and development to regulate the numbers of cells allowed to complete the differentiation pathway. In situations when more cells are needed, suppression of apoptosis enlarges the cell pool in the differentiation pathway, thus providing a mechanism for rapidly increasing cell numbers [1][2][3]. For polymorphonuclear leukocytes (PMN), it also appears to provide a mechanism for clearing cells from tissue sites without further propagation of inflammation, a crucial effect for orderly progression from injury through inflammation to healing [3].…”

Section: Introductionmentioning

confidence: 99%

Membrane depolarization and depletion of intracellular calcium stores are associated with delay of apoptosis in human neutrophils

Chacón-Cruz

Oelberg

Davis

et al. 1998

Journal of Leukocyte Biology

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Apoptosis occurs rapidly in human polymorphonuclear leukocytes (PMN) after exposure to 1 mM cycloheximide (CHX). We examined whether this form of stimulated apoptosis altered either resting cytosolic free Ca 2؉ concentrations ([free Ca]) or membrane potential ( ) in PMN and found no significant effects. However, manipulation of either PMN intracellular Ca 2؉ stores or was found to delay CHX-induced apoptosis. Depletion of PMN intracellular Ca 2؉ stores with thapsigargin caused membrane depolarization and significantly delayed CHX-induced apoptosis based on both morphological and annexin-V-fluorescein isothiocyanate binding criteria. Short-term suspension (4 h) of PMN in Ca 2؉ -free buffer depleted internal Ca 2؉ stores, induced membrane depolarization at 2.5 h, and delayed spontaneous (24 h) apoptosis but had no effect on CHX-induced apoptosis. Rapid membrane depolarization with 150 mM KCl buffer significantly delayed CHX-induced apoptosis, suggesting that depolarization rather than Ca 2؉ stores depletion was the crucial event. Timing experiments revealed that depolarization within 12 min of CHX exposure significantly delayed apoptosis. Collectively, these observations suggest an early -sensitive step in the apoptosis pathway initiated by CHX. CHX exposure alone does not alter either resting PMN [free Ca] or ; accompanying depolarization of plasma membrane (either electrochemically or via depletion of internal Ca 2؉ stores) delays CHX-induced apoptosis in a time-dependent manner. J. Leukoc. Biol. 64: 759-766; 1998.

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“…Rheumatoid arthritis and different cancer types are the best examples for too little apoptosis. Ischemic heart disease, AIDS and neurodegenerative diseases such as Alzheimer's and Parkinson's are the best examples for too much apoptosis [8,9].…”

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confidence: 99%

Evaluation of annexin V and Calcein-AM as markers of mononuclear cell apoptosis during human immunodeficiency virus infection

Palma¹,

Baggio²,

Spada³

et al. 2008

Braz J Infect Dis

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Evaluation of apoptosis by flow cytometry is generally accomplished by methods that use annexin V-FITC as vital dye, which access phosphatidylserine exposed on the external membrane at the beginning of this process. In addition, the concomitant use of propidium iodide makes possible to verify the characteristic nuclear alterations in the late stages of apoptosis, as a consequence of the increase in membrane permeability. On the other hand, the use of calcein-AM in association with ethidium homodimer (EthD-1) allows the evaluation of cell apoptosis through detection of esterase activity and cellular membrane physical and chemical alterations. The aim of this study was to compare the sensibility of calcein-AM and EthD-1 with annexin V-FITC and propidium iodide for early apoptosis evaluation in peripheral blood mononuclear cell culture, obtained from HIV-infected patients. Apoptosis and cellular viability were detected and quantified by flow cytometry after 24 and 48 hours incubation times. Our results showed that calcein-AM/EthD-1 was more sensitive for apoptotic cell quantification in both incubation times than annexin V-FITC/propidium iodide (mean of 46.95% ± 3.56, p < 0.0001, for 24 hours and mean of 37.67% ± 2.47, p < 0.0014 for 48 hours), besides allowing to clearly define viable, apoptotic and dead cell populations. Key-Words: Apoptosis, flow cytometry, annexin V, propidium iodide, calcein-AM, ethidium homodimer. Abbreviations: Calcein-AM, calcein acetoxymethyl ester; EthD-1, ethidium homodimer; FITC, fluorescein isothiocyanate.

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Cell Suicide in Health and Disease

Cited by 167 publications

References 0 publications

Caspase-3 Activity as a Prognostic Factor in Colorectal Carcinoma

Caspase-3 Activity as a Prognostic Factor in Colorectal Carcinoma

Membrane depolarization and depletion of intracellular calcium stores are associated with delay of apoptosis in human neutrophils

Evaluation of annexin V and Calcein-AM as markers of mononuclear cell apoptosis during human immunodeficiency virus infection

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