BDNF‐deficiency upregulates SIRT2 expression but does not affect cellular metabolism in mouse retina

• Published in: Acta ophthalmologica (Oxford, England) Vol. 89; no. s248
• Main Authors: PODRACKA, L, VEHANEN, K, TUULOS, T, RÖNKKO, S, KAARNIRANTA, K, UUSITALO, H, KALESNYKAS, G
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-09-2011; Wiley Subscription Services, Inc
• Subjects: Age; Brain-derived neurotrophic factor; Cell survival; Deacetylation; Energy metabolism; Enzymes; Longevity; Metabolism; NAD; NADH; Neurotrophic factors; Paraffin; Retina; SIRT1 protein; Sirtuins; Tubulin; Western blotting
• ISSN: 1755-375X; 1755-3768
• DOI: 10.1111/j.1755-3768.2011.2137.x

Purpose Brain derived neurotrophic factor (BDNF) is essential for cell development, function and survival. Mammalian sirtuins (SIRT) are deacetylase enzymes that are known to play an important role in longevity. In the present study we aimed to compare SIRT1 and SIRT2 expression in retinas of mice that lack brain derived neurotrophic factor (BDNF+/‐) and their wild type littermates (WT) at young age in relation to cellular metabolism.
Methods Eyes from 2‐months old WT and BDNF+/‐ mice (The Jackson Laboratory, Bar Harbor, ME, USA) were used. SIRT1 and SIRT2 protein levels in retina were determined by Western blotting. Paraffin‐embedded retinal sections were immunostained for SIRT1 and SIRT2 to determine their localisation and abundance in various retinal layers. Metabolic state of mouse retinal cells was assessed by measuring NAD+, NADH and total NAD levels using resazurin‐based assay.
Results Western blot analysis of the whole retina showed that SIRT1 expression is similar in WT and BDNF+/‐ mice. However, there was a significant upregulation of SIRT2 protein level in BDNF+/‐ mice compared to WT littermates. Assessment of NAD+, NADH and total NAD levels showed similar cellular metabolic state in retinas of WT and BDNF+/‐ mice.
Conclusion Our results indicate increased tubulin deacetylation in retinas of BDNF+/‐ mice, which is independent from cellular energy metabolism.