Differential expression of sirtuin family members in the developing, adult, and aged rat brain

Abstract

The sirtuins are NAD+-dependent protein deacetylases and/or ADP-ribosyltransferases that play roles in metabolic homeostasis, stress response and potentially aging. This enzyme family resides in different subcellular compartments, and acts on a number of different targets in the nucleus, cytoplasm and in the mitochondria. Despite their recognized ability to regulate metabolic processes, the roles played by specific sirtuins in the brain—the most energy demanding tissue in the body—remains less well investigated and understood. In the present study, we examined the regional mRNA and protein expression patterns of individual sirtuin family members in the developing, adult, and aged rat brain. Our results show that while each sirtuin is expressed in the brain at each of these different stages, they display unique spatial and temporal expression patterns within the brain. Further, for specific members of the family, the protein expression profile did not coincide with their respective mRNA expression profile. Moreover, using primary cultures enriched for neurons and astrocytes respectively, we found that specific sirtuin members display preferential neural lineage expression. Collectively, these results provide the first composite illustration that sirtuin family members display differential expression patterns in the brain, and provide evidence that specific sirtuins could potentially be targeted to achieve cell-type selective effects within the brain.

Caloric restriction, resveratrol and melatonin: Role of SIRT1 and implications for aging and related-diseases

“…SIRT1, located in the nucleus, is the family member sharing the most homology to Sir2, is considered to be its orthologue and is the most studied (Haigis and Guarente, 2006). Despite this, in recent years the other sirtuins, such as the mitochondrial sirtuin 3, also received significant attention regarding its actions on different aspects of cellular regulation (Someya et al, 2010;Ingram and Roth, 2015;Herskovits and Guarente, 2014;Sidorova-Darmos et al, 2014). SIRT1 can deacetylate histones (Imai et al, 2000;Vaquero et al, 2004) as well as a large number of substrates (Yamamoto et al, 2007), including the tumor suppressor p53 protein, the DNA repair factor Ku70, nuclear factor-B (NF-B), the signal transducer and activator of transcription 3 and the FOXO family of forkhead transcription factors, proteins that affect stress resistance in cells (Luo et al, 2001;Vaziri et al, 2001;Brunet et al, 2004;Cohen et al, 2004;Motta et al, 2004;Yeung et al, 2004;Bernier et al, 2011).…”

Astrocyte-derived lipoxins A4 and B4 promote neuroprotection from acute and chronic injury

“…The number of cell bodies and ratio of neurites/cell was established for each acquired frame, with 32 frames scored from each experimental group. Primary cortical neurons were cultured essentially as described (67). Briefly, cortices were dissected from E16 mouse embryos on ice.…”

Sirtuin 3 regulates Foxo3a-mediated antioxidant pathway in microglia

“…It is reported to be differentially expressed in different regions and different stages of the developing and adult rat brains and its expression was found to be regulated in the cortical neurons and astrocytes (Sidorova-Darmos et al, 2014). Sirt3 has been shown to have a major involvement in ROS regulation (Sundaresan et al, 2009).…”

“…Sirtuin 3 (Sirt3), primarily known to be a protein/ histone deacetylase is widely expressed in most cell types including cells of the CNS (Kim et al, 2011;Sidorova-Darmos et al, 2014). It is reported to be differentially expressed in different regions and different stages of the developing and adult rat brains and its expression was found to be regulated in the cortical neurons and astrocytes (Sidorova-Darmos et al, 2014).…”