Sex-Dependent and Aging Adaptive Homeostasis in Response to Oxidative Stress

Undergraduate #63
Discipline: Biological Sciences
Subcategory: Cell and Molecular Biology

Sarah Wong - University of Southern California
Co-Author(s): Laura Corrales-Diaz Pomatto, John Tower, and Kelvin J.A. Davies, University of Southern California, Los Angeles

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Adaptation to oxidative stress not only differs between the sexes, but also declines with age. These two frameworks offer insight to the underlying mechanisms for survival differences between males and females, and between the young and the old. These differences are maintained across species from the common fruit fly, Drosophila melanogaster, to humans. In this study, we evaluated the oxidative-stress adaptive responses, an example of physiological Adaptive Homeostasis as recently defined (Davies, K.J.A. Adaptive Homeostasis, Molecular Aspects of Medicine 49, 1–7, 2016), to hydrogen peroxide (H 2 O 2 ) and redox-cycling agents, specifically paraquat, 2-methyl- 1,4 napthoquinone (menadione), and 2,3-Dimethoxy-1,4- naphthoquinone (DMNQ). To investigate adaptation, we focused on three common laboratory D. melanogaster strains: Oregon-R, w[1118], and Canton-S. The flies were pretreated with stimulatory, low doses of H 2 O 2 , paraquat, menadione or DMNQ before receiving a toxic challenge dose. We find that females show adaptive increases in survival after exposure to small amounts of hydrogen peroxide (H 2 O 2 ). Conversely, males exhibit no adaptive response to H 2 O 2. Males did exhibit adaptive responses to the redox cycling agents, however, whereas females did not. The same trend was observed when comparing older flies with younger flies, although the adaptive ability is significantly decreased. To assess the changes in proteolytic activity and the expression of the 20S Proteasome, fluorogenic peptide assays and Western blots were performed. Our work suggests that males may potentially use an alternative mechanism in order to induce their adaptive response to redox cycling agents, emphasizing the need to evaluate sex as critical biological variable in future studies.

Funder Acknowledgement(s): NIH/NIEHS R01 grant ES03598-25 (PI: Davies, K.J.A.)

Faculty Advisor: Kelvin J.A. Davies, kelvin@usc.edu

Role: Assisted Ph.D. student with the tossing, sorting of fruit flies by sex, and treatment of sample groups; grinded and lysed samples for assays; handled kill curve assays of challenge doses and contributed to data input; performed bicinchoninic acid assays, western blots and fluorogenic peptide cleavage assays for 3 wild-type strains with 3 separate treatment groups; currently contributing to writing of paper for future publication