Stress response to genotoxic agents and to infection
Date
2012-10-08
Authors
Hull, Rodney
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Abstract
Insects have evolved various physiological responses to cope with stressors such as
pathogens, toxins and environmental factors. It is known that the responses resulting
from infection or DNA damage share some of the same pathways. Exposure of
Drosophila melanogaster and the dung beetle Euoniticellus intermedius to stress led
to changes in the expression of proteins involved in metabolism, development, protein
degradation, mRNA processing and stress responses. Stress responses in D.
melanogaster are well characterised. However, the role played by Drosophila p53
(Dmp53) and a member of the retinoblastoma binding protein 6 (RBBP6) family,
Snama, are unknown. Snama has been proposed to play a role in Dmp53 regulation.
Following DNA damage we investigated the role of Dmp53 and Snama. Flies
recovering from camptothecin treatment display a glycolytic flux, involving a
metabolic shift, different to that observed in cancer cells. Camptothecin treatment
leads to an increase in the mortality of both sexes. Furthermore, females show a
specific decrease in fecundity which is due to an increase in Dmp53 dependent
apoptosis in the ovaries and is accompanied by a depletion of Snama and an increase
in Dmp53 transcripts. Expression data indicated that Dmp53 activity may be largely
regulated at the protein level. Bypassing glycolysis through methyl pyruvate
supplementation led to differential expression of Dmp53 and Snama and improved
reproduction and embryonic development. These results highlight differences
between the metabolic strategies used by cancerous and non-cancerous cells which
may be exploited in future chemotherapies. While immune responses amongst insect
orders are evolutionarily conserved, many remain uncharacterised. To investigate the
immune system of an organism that lives in a microbe rich environment, E.
intermedius was infected with the fungal pathogen Beauveria bassiana. This resulted
in decreased lifespan and fecundity. Homologs of proteins involved in the immune
response of insects were identified in E. intermedius, including a member of the Toll
family of proteins, an insect defensin (present in the hemolymph) as well as a homolog of the serine protease Persephone. These results show that immune
signalling pathways are conserved in this dung beetle.