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dc.contributor.advisorMoore, D. Blaine, 1972-
dc.contributor.authorMyers, Barret J.
dc.descriptioniv, 35 p.
dc.descriptionDiebold Scholar
dc.description.abstractAlcohol abuse is known to promote cell death in many tissues, including the liver and nervous system, however its precise sub-cellular mechanism remains unclear. Ethanol induces apoptosis in cells via a caspase-dependent mechanism. Control of caspase activity, and thus apoptosis, is directly modulated by the Bcl-2 family of proteins, which includes both pro- and anti-apoptotic members. Anti-apoptotic Bcl-2 protects cells from apoptosis by inhibiting caspase activation. Bcl-2 is known to be localized both to mitochondria and the ER and overexpression of ER-localized Bcl-2 has been shown to significantly rescue cells from ethanol-induced apoptosis. Caspase-9 and caspase-12 are thought to be downstream of mitochondria and the endoplasmic reticulum respectively, however it is unknown which of these caspases is activated in ethanol-induced apoptosis. Chinese hamster ovary cells (CHO695) were treated with a pan-caspase inhibitor, a caspase-9 inhibitor or a caspase-12 inhibitor, and then treated with 1.5 M ethanol in order to determine the sub-cellular mechanism of rescue from ethanol toxicity. An MTT assay was used to measure cell viability in response to ethanol treatment. Treatment with the pan-inhibitor provided CHO695 cells with significant rescue from ethanol toxicity. Caspase-12 inhibition conferred significant protection from ethanol toxicity to cells, while caspase-9 inhibition did not provide significant rescue. Caspase-12 and pan-caspase inhibition were not statistically different. This work suggests that ethanol-induced apoptosis does not occur via a mitochondrial stress pathway and caspase-9 activation, but rather through an ER-stress pathway and subsequent caspase-12 activation. Future work should clarify the role of the ER in ethanol toxicity contributing to both liver and neuronal cell death associated with alcohol abuse.en_US
dc.description.sponsorshipHoward Hughes Medical Institute
dc.publisherKalamazoo Collegeen_US
dc.relation.ispartofKalamazoo College Biology Senior Individualized Projects Collection
dc.relation.ispartofseriesSenior Individualized Projects. Biology.
dc.rightsU.S. copyright laws protect this material. Commercial use or distribution of this material is not permitted without prior written permission of the copyright holder.
dc.titleInhibition of ER-Stress Associated Caspase-12 Rescues Cultured Cells from Ethanol Toxicityen_US

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  • Biology Senior Individualized Projects [1489]
    This collection includes Senior Individualized Projects (SIP's) completed in the Biology Department. Abstracts are generally available to the public, but PDF files are available only to current Kalamazoo College students, faculty, and staff.

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