Fig. 1.

ERK1/2 inhibition-induced PGC-1α and miR34a regulation and the connection to the NAD⁺ salvage pathway through the enzyme, NAMPT. Illustrative connections between trametinib pretreatment and inhibition of ERK1/2 phosphorylation and the NAD salvage pathway. a By inhibiting ERK1/2 phosphorylation before renal IR AKI renal dysfunction is prevented. Trametinib treatment mediated mitochondrial biogenesis through an increase in PGC-1α non-acetylated protein and ameliorated NAD⁺ and the rate-limiting NAD salvage enzyme, NAMPT, loss following IR by decreasing miR34a. miR34a did not change due to IR alone. b Illustration of NAD generation from both the de novo pathway and the salvage pathway