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Event: 867

Key Event Title

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

Decrease, Intracellular pH

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
Decrease, Intracellular pH
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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
Cellular

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
eukaryotic 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

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
regulation of intracellular pH decreased

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
pH Induced Nasal Tumors MolecularInitiatingEvent Justin Teeguarden (send email) Open for citation & comment EAGMST Under Review

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
Rattus sp. ABTC 42503 Rattus sp. ABTC 42503 High NCBI
mouse Mus musculus High NCBI
human Homo sapiens Moderate NCBI

Life Stages

An indication of the the relevant life stage(s) for this KE. More help

Sex Applicability

An indication of the the relevant sex for this KE. More help

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

Cells regulate proton concentrations within a narrow range with intracellular buffers and plasma membrane-bound transportors such as the Na+/H+ antiportor, and others such as the vacuolar proton pump[1]. Increased production or reduced buffering of protons can exceed homeostatic control mechanisms and cause intracellular acidification.

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

Intracellular pH can be measured in vitro using membrane permeable pH sensitive dyes, [2] and in vivo using ratiometric NIR fluorescent probes[3]. pH change can be measured using pH sensitive dyes distributed to the intracellular space, as was done in liver cells and nasal tissue and oral cavity epithelia[4].

Domain of Applicability

A description of the scientific basis for the indicated domains of applicability and the WoE calls (if provided).  More help
All cells regulate intracellular pH and produce protons as a normal byproduct of metabolism.

References

List of the literature that was cited for this KE description. More help
  1. Izumi, Torigoe, Ishiguchi, Uramoto, Yoshida, Tanabe, Ise, Murakami, Yoshida, Nomoto and Kohno (2003). Cellular pH regulators: potentially promising molecular targets for cancer chemotherapy. Cancer Treat Rev. 29: 541-549
  2. Bogdanffy (2002). Vinyl acetate-induced intracellular acidification: implications for risk assessment. Toxicol Sci. 66: 320-326, Lantz, Orozco and Bogdanffy (2003). Vinyl acetate decreases intracellular pH in rat nasal epithelial cells. Toxicol Sci. 75: 423-431, Nakamoto, Wagner, Melvin and Bogdanffy (2005). Vinyl acetate induces intracellular acidification in mouse oral buccal epithelial cells. Toxicol Lett. 158: 116-121
  3. Li, Wang, Yang, Zhao, Yuan, Zheng and Yang (2015). Hemicyanine-based high resolution ratiometric near-infrared fluorescent probe for monitoring pH changes in vivo. Anal Chem. 87: 2495-2503
  4. Bogdanffy (2002). Vinyl acetate-induced intracellular acidification: implications for risk assessment. Toxicol Sci. 66: 320-326, Lantz, Orozco and Bogdanffy (2003). Vinyl acetate decreases intracellular pH in rat nasal epithelial cells. Toxicol Sci. 75: 423-431, Nakamoto, Wagner, Melvin and Bogdanffy (2005). Vinyl acetate induces intracellular acidification in mouse oral buccal epithelial cells. Toxicol Lett. 158: 116-121
  5. Bogdanffy (2002). Vinyl acetate-induced intracellular acidification: implications for risk assessment. Toxicol Sci. 66: 320-326
  6. Lantz, Orozco and Bogdanffy (2003). Vinyl acetate decreases intracellular pH in rat nasal epithelial cells. Toxicol Sci. 75: 423-431, Nakamoto, Wagner, Melvin and Bogdanffy (2005). Vinyl acetate induces intracellular acidification in mouse oral buccal epithelial cells. Toxicol Lett. 158: 116-121
  7. Simon, Filser and Bolt (1985). Metabolism and pharmacokinetics of vinyl acetate. Arch Toxicol. 57: 191-195, Bogdanffy and Taylor (1993). Kinetics of nasal carboxylesterase-mediated metabolism of vinyl acetate. Drug Metabolism and Disposition. 21: 1107-1111, Bogdanffy, Sarangapani, Kimbell, Frame and Plowchalk (1998). Analysis of vinyl acetate metabolism in rat and human nasal tissues by an in vitro gas uptake technique. Toxicological Sciences. 46: 235-246, Bogdanffy, Manning and Sarangapani (1999). High-affinity nasal extraction of vinyl acetate vapor is carboxylesterase dependent. Inhal Toxicol. 11: 927-941, Morris, Symanowicz and Sarangapani (2002). Regional distribution and kinetics of vinyl acetate hydrolysis in the oral cavity of the rat and mouse. Toxicol Lett. 126: 31-39