Knoops, BernardQuintana Latorre, JohannaJohannaQuintana Latorre2025-05-142025-05-142025-05-142023https://hdl.handle.net/2078.2/35462In order to prevent cellular damage induced by increased production of reactive oxygen species, aerobic organisms have evolved intricate antioxidant defense mechanisms. High levels of ROS induce oxidative stress which is damaging to lipids, proteins, and DNA. Oxidative stress has, therefore, been associated with the pathogenesis of various disorders. Amongst antioxidant enzymatic defense, peroxiredoxin-5 (PRDX5) has proved to be highly efficient in protecting the cell from oxidative stress. Surprisingly, a previous investigation led by a master's student suggested that astrocyte 1321N1 cells with a PRDX5 knockout (PRDX5 KO) exhibited a significantly enhanced resistance to oxidative stress induced by rotenone, in comparison to their PRDX5 wild-type (PRDX5 WT) counterparts. This suggests that an alternative mechanism could compensate for the loss of PRDX5 and increase cell survival in KO cells following exposure to rotenone. Prior investigations have elucidated an interplay between PRDXs and STAT3 in oxidative stress conditions. Thus, this study aims to investigate the involvement of STAT3 as an underlying mechanism in the increased resistance to rotenone-induced oxidative stress in 1321N1 PRDX5 KO cells. Our data corroborates previous findings in 1321N1 cells. Moreover, by extending this inquiry to oligodendrocytes, we found that HOG PRDX5 KO cells did not respond in the same manner implying that WT astrocytes are more susceptible to rotenone-induced oxidative stress. In addition to this, we confirmed that rotenone-induced apoptosis through the intrinsic apoptotic pathway, and that it induced apoptosis rather than secondary necrosis in the 1321N1 cell line. Moreover, our investigations of STAT3 expression and activation suggest that it may not play a direct role in this context. Further exploration demonstrated that anti-apoptotic targets of STAT3, Bcl-2, and Bcl-xL were downregulated, whereas c-Myc proto-oncogene and survivin were upregulated. No other participants could be found to play a part in this compensatory mechanism. Finally, in 1321N1 cells, no interaction between PRDX5 and STAT3 was evidenced. Taken together, our data leads us to propose the existence of a compensatory mechanism that safeguards cells against oxidative stress induced by rotenone. However, this mechanism does not seem to operate via the JAK/STAT3 pathway.PRDX5STAT3rotenoneoxidative stressastrocytesROStext::thesis::master thesisthesis:43542