Cellular Stress and Thioredoxin (AY22/23)

Gabelmann, John

Student Work

Cellular Stress and Thioredoxin (AY22/23)

Public Deposited

Stress Granules (SGs) are cytoplasmic aggregates of mRNA, protein, and other cellular components that form as a result of different types of cellular stress. Many heavy metals, such as arsenic, exert toxicity on cells via oxidative stress, causing stress granules to form. Arsenic Methyltransferase (AS3MT) can methylate arsenic, reducing the oxidative stress it causes. Thioredoxin (TRX1) acts as a general sink for oxidative species, sequestering arsenite and reducing the oxidative stress it causes. Fas Apoptotic Inhibitory Molecule (FAIM) can sequester disordered proteins. It is hypothesized that the characteristics of AS3MT, TRX1 and FAIM can prevent SG formation through prevention of aggregation via G3BP1, one of the primary protein drivers for SG formation. To test this hypothesis, AS3MT, TRX1 or FAIM was expressed by transient transfection in cultured human cells (HeLas), and SG formation was assessed by fluorescence microscopy.. The results showed preliminary evidence that these proteins suppress SG formation, although more testing with refined experimentation is needed to fully assess the degree of suppression. Additionally, several proteins related to the alleviation of oxidative stress, including TRX1, TXNRD1, GPX4 and GSR, were found to co-localize with G3BP1 in SGs, indicating that these proteins may be important functional components of SGs. Overall, the results of this experiment and refined protocol will greatly help understanding of SG regulation in response to oxidative stress.

This report represents the work of one or more WPI undergraduate students submitted to the faculty as evidence of completion of a degree requirement. WPI routinely publishes these reports on its website without editorial or peer review.

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