Linking mechanistic and behavioral responses to sublethal esfenvalerate exposure in the endangered delta smelt; Hypomesus transpacificus (Fam. Osmeridae)

Connon, Richard E; Geist, Juergen; Pfeiff, Janice; Loguinov, Alexander V; D'Abronzo, Leandro S; Wintz, Henri; Vulpe, Christopher D; Werner, Inge

iii Apoptotic responses Caspases (cysteine-aspartic acid protease) belong to a family of cysteine proteases that cleave other proteins, such as the precursor forms of the inflammatory cytokines interleukin 1-β and interleukin 18, into active mature peptides and are also involved in programmed cell death; or apoptosis [60] . Enzymatic activity requires an aspartic acid residue, and plays a critical role in the regulation of proinflammatory cytokines [61] that are associated with septic shock and autoimmune syndromes [62] . Upregulation of proinflammatory cytokines were reported in viral infected salmon, which further increased in expression following esfenvalerate exposure [63] . Caspases contribute to the pathogenesis of neurodegenerative disorders such as ischemia, Krabbes and Huntington's diseases, Alzheimer's, and other leukodystrophic diseases resulting in neural degeneration [64, 65] . Moreover, caspase inhibitors have been suggested as therapeutic treatments for neurodegenerative diseases [66] . Low concentrations of esfenvalerate; 0.0313 μg.L -1 , significantly induced caspase-3 expression 2-fold (t-test, p = 0.002) in 10-d old delta smelt. As caspases are activated by aspartic acid, induction may be suggestive of increases in substrate residues, along with inflammatory cytokines, probable effects upon the immune system, and subsequent neurodegeneration. Furthermore, a decrease in ASPA expression could be suggestive of reduced breakdown of NNA to aspartate and acetate, required as substrate for caspase activity, and synthesis of proteins required in repair mechanisms.