The effects of Nordihydroguaiaretic acid and the function of HDAC‐6 in the model organism Caenorhabditis elegans

To explore the effects of Nordihydroguairetic Acid (NDGA) and the role of the histone deacetylase HDAC‐6 in oxidative stress responses, we are performing RNA interference (RNAi) in the model organism C. elegans . NDGA is a polyphenolic lignan known for its antioxidant properties and is found in large quantities in the long‐lived desert plant Larrea tridentata . HDAC‐6 is an enzyme involved in the acetylation of α‐tubulin microtubules, Hsp90 and the redox regulatory protein peroxiredoxin (Prx). Preliminary results indicate that cultivation of worms on 1mM NDGA‐enhanced medium results in reduced body size with no apparent affect on fertility. An RNAi construct of 233bp targeting exon 8 of the HDAC‐6 gene on chromosome IV was created by amplifying genomic DNA (gDNA) from wild‐type C. elegans . The amplified product was cloned into the RNAi expression vector pL4440. The vector contains T7 RNA polymerase promoters flanking the multiple cloning site, enabling the production of double‐stranded RNA upon induction. Ongoing experiments will include cellular assays to elucidate a possible phenotype related to the role of HDAC‐6 in oxidative stress responses.