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Event: 2124

Key Event Title

A descriptive phrase which defines a discrete biological change that can be measured. More help

increased, Bax expression

Short name
The KE short name should be a reasonable abbreviation of the KE title and is used in labelling this object throughout the AOP-Wiki. More help
increased, Bax
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Biological Context

Structured terms, selected from a drop-down menu, are used to identify the level of biological organization for each KE. More help
Level of Biological Organization
Molecular

Cell term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Cell term
cell

Organ term

The location/biological environment in which the event takes place.The biological context describes the location/biological environment in which the event takes place.  For molecular/cellular events this would include the cellular context (if known), organ context, and species/life stage/sex for which the event is relevant. For tissue/organ events cellular context is not applicable.  For individual/population events, the organ context is not applicable.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Organ term
organ

Key Event Components

The KE, as defined by a set structured ontology terms consisting of a biological process, object, and action with each term originating from one of 14 biological ontologies (Ives, et al., 2017; https://aopwiki.org/info_pages/2/info_linked_pages/7#List). Biological process describes dynamics of the underlying biological system (e.g., receptor signalling).Biological process describes dynamics of the underlying biological system (e.g., receptor signaling).  The biological object is the subject of the perturbation (e.g., a specific biological receptor that is activated or inhibited). Action represents the direction of perturbation of this system (generally increased or decreased; e.g., ‘decreased’ in the case of a receptor that is inhibited to indicate a decrease in the signaling by that receptor).  Note that when editing Event Components, clicking an existing Event Component from the Suggestions menu will autopopulate these fields, along with their source ID and description.  To clear any fields before submitting the event component, use the 'Clear process,' 'Clear object,' or 'Clear action' buttons.  If a desired term does not exist, a new term request may be made via Term Requests.  Event components may not be edited; to edit an event component, remove the existing event component and create a new one using the terms that you wish to add.  Further information on Event Components and Biological Context may be viewed on the attached pdf. More help
Process Object Action
apoptosis regulator BAX increased

Key Event Overview

AOPs Including This Key Event

All of the AOPs that are linked to this KE will automatically be listed in this subsection. This table can be particularly useful for derivation of AOP networks including the KE.Clicking on the name of the AOP will bring you to the individual page for that AOP. More help
AOP Name Role of event in AOP Point of Contact Author Status OECD Status
Co-activation of IP3R and RyR to lower IQ and socio-economic burden KeyEvent Karine Audouze (send email) Under development: Not open for comment. Do not cite
AHR activation leading to POI KeyEvent Sapana Kushwaha (send email) Under development: Not open for comment. Do not cite

Taxonomic Applicability

Latin or common names of a species or broader taxonomic grouping (e.g., class, order, family) that help to define the biological applicability domain of the KE.In many cases, individual species identified in these structured fields will be those for which the strongest evidence used in constructing the AOP was available in relation to this KE. More help
Term Scientific Term Evidence Link
mouse Mus musculus High NCBI
rat Rattus norvegicus Moderate NCBI
human Homo sapiens High NCBI
Drosophila melanogaster Drosophila melanogaster High NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help
Life stage Evidence
All life stages Moderate

Sex Applicability

An indication of the the relevant sex for this KE. More help
Term Evidence
Female High

Key Event Description

A description of the biological state being observed or measured, the biological compartment in which it is measured, and its general role in the biology should be provided. More help

Bax (Bcl-2-associated X protein) is a pro-apoptotic member of the Bcl-2 family that plays a critical role in regulating apoptosis. It is primarily localized in the cytoplasm and translocates to the mitochondria during apoptotic signaling. Bax  plays a critical role in regulating apoptosis, including the apoptosis of oocytes during early development. When apoptotic signals are received, pro-apoptotic members like Bax  are activated, often through phosphorylation or cleavage (e.g., in response to cellular stress). Once activated, Bax  translocate to the outer mitochondrial membrane, where they form pores, leading to the release of cytochrome c and other apoptotic factors from the mitochondria into the cytoplasm. Increased expression of pro-apoptotic proteins (like Bax or Bad) can lead to excessive apoptosis, which might contribute to diseases such as neurodegenerative disorders, autoimmune diseases, or reproductive cell depletion (like oocyte loss).

How It Is Measured or Detected

A description of the type(s) of measurements that can be employed to evaluate the KE and the relative level of scientific confidence in those measurements.These can range from citation of specific validated test guidelines, citation of specific methods published in the peer reviewed literature, or outlines of a general protocol or approach (e.g., a protein may be measured by ELISA). Do not provide detailed protocols. More help

Immunohistochemistry (IHC) IHC detects Bax protein expression in tissue sections. After tissue fixation and antigen retrieval, Bax-specific antibodies are applied, followed by an enzyme-conjugated secondary antibody. A chromogenic substrate (e.g., DAB) generates a color reaction, allowing visualization under a microscope, which is useful for studying tissue-specific expression (4,8).

Immunofluorescence (IF) This technique is used for localizing Bax protein in cells or tissues. Fluorescently labeled primary or secondary antibodies bind to Bax, and confocal or fluorescence microscopy is used for imaging. IF provides high-resolution spatial distribution of Bax expression(6).

Quantitative Real-Time PCR (qRT-PCR) Used to measure Bax mRNA expression levels, this method involves RNA extraction, reverse transcription to cDNA, and amplification using gene-specific primers. Fluorescent dyes or probes (e.g., SYBR Green, TaqMan) help quantify Bax mRNA in real-time, making it a sensitive method for gene expression analysis (6,7).

Northern blotting

This is a standard approach for detecting Bax mRNA expression. RNA is isolated from tissues or cells, separated by size using gel electrophoresis, transferred to a membrane, and hybridised with a labelled Bax-specific probe. The signal indicates both the existence and size of the Bax transcripts (9).

TUNEL Assay (Indirect Method) While not directly measuring Bax, the TUNEL assay detects apoptotic DNA fragmentation, often correlated with Bax activation. It is used in ovarian apoptosis studies alongside Bax expression analysis(4,10).

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help

Taxonomic: Conserved in mammals (humans, rodents) and some invertebrates (Drosophila).

Life Stage: Relevant in embryonic development (organogenesis)(12, 14), adulthood (toxicology, cancer)(15,16,17) and aging (neurodegeneration, ovarian atrophy)(13).

Sex Applicability: Critical in female reproductive toxicity (ovarian atresia) and male spermatogenesis, but applies broadly across tissues in both sexes.

References

List of the literature that was cited for this KE description. More help
  1. Hussein MR. Apoptosis in the ovary: molecular mechanisms. Hum Reprod Update. 2005;11(2):162-77.
  2. Pawlowski J, Kraft AS. Bax-induced apoptotic cell death. Proc Natl Acad Sci U S A. 2000;97(2):529-31.
  3. Greenfeld CR, Pepling ME, Babus JK, Furth PA, Flaws JA. BAX regulates follicular endowment in mice. Reproduction. 2007;133(5):865-76.
  4. Albamonte MS, Willis MA, Albamonte MI, Jensen F, Espinosa MB, Vitullo AD. The developing human ovary: immunohistochemical analysis of germ-cell-specific VASA protein, BCL-2/BAX expression balance and apoptosis. Hum Reprod. 2008;23(8):1895-901.
  5. Perez GI, Jurisicova A, Wise L, Lipina T, Kanisek M, Bechard A, et al. Absence of the proapoptotic Bax protein extends fertility and alleviates age-related health complications in female mice. Proc Natl Acad Sci U S A. 2007;104(12):5229-34.
  6. Ke F, Bouillet P, Kaufmann T, Strasser A, Kerr J, Voss AK. Consequences of the combined loss of BOK and BAK or BOK and BAX. Cell Death Dis. 2013;4(6):e650.
  7. Rhon-Calderón EA, Toro CA, Lomniczi A, Galarza RA, Faletti AG. Changes in the expression of genes involved in the ovarian function of rats caused by daily exposure to 3-methylcholanthrene and their prevention by α-naphthoflavone. Arch Toxicol. 2018;92(2):907-19.
  8. Pru JK, Kaneko-Tarui T, Jurisicova A, Kashiwagi A, Selesniemi K, Tilly JL. Induction of proapoptotic gene expression and recruitment of p53 herald ovarian follicle loss caused by polycyclic aromatic hydrocarbons. Reprod Sci. 2009;16(4):347-56.
  9. Tai YT, Lee S, Niloff E, Weisman C, Strobel T, Cannistra SA. BAX protein expression and clinical outcome in epithelial ovarian cancer. J Clin Oncol. 1998;16(8):2583-90.
  10. Gaumer S, Guénal I, Brun S, Théodore L, Mignotte B. Bcl-2 and Bax mammalian regulators of apoptosis are functional in Drosophila. Cell Death & Differentiation. 2000;7(9):804-14
  11. Russell LD, Chiarini-Garcia H, Korsmeyer SJ, Knudson CM. Bax-dependent spermatogonia apoptosis is required for testicular development and spermatogenesis. Biol Reprod. 2002;66(4):950-8.
  12. Fish EW, Mendoza-Romero HN, Love CA, Dragicevich CJ, Cannizzo MD, Boschen KE, et al. The pro-apoptotic Bax gene modifies susceptibility to craniofacial dysmorphology following gastrulation-stage alcohol exposure. Birth Defects Res. 2022;114(19):1229-43.
  13. MacGibbon GA, Lawlor PA, Sirimanne ES, Walton MR, Connor B, Young D, et al. Bax expression in mammalian neurons undergoing apoptosis, and in Alzheimer's disease hippocampus. Brain Res. 1997;750(1-2):223-34.
  14. Sun F, Akazawa S, Sugahara K, Kamihira S, Kawasaki E, Eguchi K, Koji T. Apoptosis in normal rat embryo tissues during early organogenesis: the possible involvement of Bax and Bcl-2. Arch Histol Cytol. 2002;65(2):145-57.
  15. Lee DH, Szczepanski M, Lee YJ. Role of Bax in quercetin-induced apoptosis in human prostate cancer cells. Biochem Pharmacol. 2008;75(12):2345-55.
  16. Cory S, Adams JM. Killing cancer cells by flipping the Bcl-2/Bax switch. Cancer Cell. 2005;8(1):5-6.
  17. Liu Z, Ding Y, Ye N, Wild C, Chen H, Zhou J. Direct Activation of Bax Protein for Cancer Therapy. Med Res Rev. 2016;36(2):313-41.