API

Event: 1262

Key Event Title

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Apoptosis

Short name

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Apoptosis

Biological Context

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Level of Biological Organization
Cellular

Cell term

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Cell term
cell


Organ term

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Organ term
organ


Key Event Components

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Process Object Action
apoptotic process increased

Key Event Overview


AOPs Including This Key Event

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Stressors

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Taxonomic Applicability

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Life Stages

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Life stage Evidence
Not Otherwise Specified High

Sex Applicability

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Term Evidence
Unspecific High

Key Event Description

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Apoptosis, also called as “physiological cell death”, is involved in cell turnover, physiological involution and atrophy of various tissues and organs [Kerr, 1972). The formation of apoptotic bodies involves marked condensation of both nucleus and cytoplasm, nuclear fragmentation, and separation of protuberances [Kerr, 1972]. Apoptosis is characterized by DNA ladder and chromatin condensation. Several stimuli such as hypoxia, nucleotides deprivation, chemotherapeutical drugs, DNA damage, and mitotic spindle damage induce p53 activation, leading to p21 activation and cell cycle arrest [Pucci, 2000]. The SAHA or TSA treatment on neonatal human dermal fibroblasts (NHDFs) for 24 or 72 hrs inhibited proliferation of the NHDF cells [Glaser, 2003]. Considering that the acetylation of histone H4 was increased by the treatment of SAHA for 4 hrs, histone deacetylase inhibition may be involved in the inhibition of the cell proliferation [Glaser, 2003]. The impaired proliferation was observed in HDAC1-/- ES cells, which was rescued with the reintroduction of HDAC1 [Zupkovitz, 2010]. The present AOP focuses on p21 pathway leading to apoptosis, however, the alternative pathway such as NF-kB signaling pathways may be involved in apoptosis of spermatocytes [Wang, 2017].


How It Is Measured or Detected

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The apoptosis is detected with the expression alteration of procaspases 7 and 3 by Western blotting using antibodies [Parajuli, 2014]. The apoptosis is measured with down-regulation of anti-apoptotic gene baculoviral inhibitor of apoptosis protein repeat containing 2 (BIRC2, or cIAP1) [Parajuli, 2014]. Apoptotic nucleosomes were detected using Cell Death Detection ELISA kit, which were calculated as absorbance subtraction at 405 nm and 490 [Parajuli, 2014]. Cell viability was measured with live cell number changes using the CellTiter-Glo Luminescent Cell Viability Assay [Parajuli, 2014]. Cleavage of PARP was detected with Western blotting [Parajuli, 2014]. The proliferation/viability of NHDFs was measured with Alamar-Blue [modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] [Glaser, 2003]. Proliferation of the HDAC-/- ES cells was determined with crystal violet and measurement of absorbance at 595 nm [Zupkovitz, 2010]. Caspase-3 and caspase-9 activity is measured with the enzyme-catalyzed release of p-nitroanilide (pNA) and quantified at 405 nm [Wu, 2016]. Apoptosis is measured with Annexin V-FITC probes, and the relative percentage of Annexin V-FITC-positive/PI-negative cells is analyzed by flow cytometry [Wu, 2016].


Domain of Applicability

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The apoptosis and proliferation inhibition induced by MAA was measured in human prostate cancer cell lines (Homo sapiens) [Parajuli, 2014]. The cell viability inhibition induced by SAHA or TSA was observed in NHDFs (Homo sapiens) [Glaser, 2003]. The proliferation of the HDAC-/- ES cells was inhibited compared to HDAC+/+ ES cells (Homo sapiens) [Zupkovitz, 2010].


Regulatory Significance of the Adverse Outcome

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References

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Kerr JFR et al. (1972) Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer 26: 239-257Pucci B et al. (2000) Cell cycle and apoptosis. Neoplasia 2:291-299

Pucci B et al. (2000) Cell cycle and apoptosis. Neoplasia 2:291-299

Glaser KB et al. (2003) Gene expression profiling of multiple histone deacetylase (HDAC) inhibitors: defining a common gene set produced by HDAC inhibition in T24 and MDA carcinoma cell lines. Mol Cancer Ther 2:151-163

Zupkovitz G et al. (2010) The cyclin-dependent kinase inhibitor p21 is a crucial target for histone deacetylase 1 as a regulator of cellular proliferation. Mol Cell Biol 30:1171-1181

Wang C et al. (2017) CD147 regulates extrinsic apoptosis in spermatocytes by modulating NFkB signaling pathways. Oncotarget 8: 3132-3143

Parajuli KR et al. (2014) Methoxyacetic acid suppresses prostate cancer cell growth by inducing growth arrest and apoptosis. Am J Clin Exp Urol 2:300-313

Wu R et al. (2016) microRNA-497 induces apoptosis and suppressed proliferation via the Bcl-2/Bax-caspase9-caspase 3 pathway and cyclin D2 protein in HUVECs. PLoS One 11: e0167052