Cellular Energy Sensor Sirt1 Augments Mapk Signaling to Promote Hypoxia/Reoxygenation-Induced Catch-up Growth in Zebrafish Embryo

Zoolog Sci. 2024 Feb;41(1):21-31. doi: 10.2108/zs230059.ABSTRACTAnimal growth is blunted in adverse environments where catabolic metabolism dominates; however, when the adversity disappears, stunted animals rapidly catch up to age-equivalent body size. This phenomenon is called catch-up growth, which we observe in various animals. Since growth retardation and catch-up growth are sequential processes, catabolism or stress response molecules may remain active, especially immediately after growth resumes. Sirtuins (Sirt1-7) deacetylate target proteins in a nicotinamide adenine dinucleotide-dependent manner, and these enzymes govern diverse alleys of cellular functions. Here, we investigated the roles of Sirt1 and its close paralog Sirt2 in the hypoxia/reoxygenation-induced catch-up growth model using zebrafish embryos. Temporal blockade of Sirt1/2 significantly reduced the growth rate of the embryos in reoxygenation, but it was not evident in constant normoxia. Subsequent gene knockdown and chemical inhibition experiments demonstrated that Sirt1, but not Sirt2, was required for the catchup growth. Inhibition of Sirt1 significantly reduced the activity of mitogen-activated kinase (Mapk) of embryos in the reoxygenation condition. In addition, co-inhibition of Sirt1- and Igf-signaling did not further reduce the body growth or Mapk activation compared to those of the Igf-signaling-alone-inhibited embryos. Furthermore, in the reoxygenation condition, Sirt1- or Igf-signaling inhibitio...
Source: Zoological Science - Category: Zoology Authors: Source Type: research