Resveratrol abolishes resistance to axonal degeneration in slow Wallerian degeneration (WldS) mice: activation of SIRT2, an NAD-dependent tubulin deacetylase. 2007

Kazuhiko Suzuki, and Tatsuro Koike
Molecular Neurobiology Laboratory, Division of Integrated Life Science, Hokkaido University Graduate School of Life Science, Sapporo 060-0810, Japan.

Resveratrol is a natural polyphenol having a wide range of biological and pharmacological activities. Here we have investigated the effect of resveratrol on neurodegeneration in cultured cerebellar granule cells from slow Wallerian degeneration (Wld(S)) mice, characteristic of substantial delay of degeneration in the distal stump of transected axons. Resveratrol diminished resistance of Wld(S) neurons to axonal degeneration induced by colchicine, a microtubule depolymerizing drug. Resveratrol also decreased the level of tubulin acetylation in Wld(S) neurons and their homogenates. This promoting effect on tubulin deacetylation was mimicked by NAD, suggesting the involvement of SIRT2, an NAD-dependent tubulin deacetylase. Indeed, resveratrol promoted tubulin deacetylation in the presence of GFP-SIRT2 but not GFP-SIRT2 N168A, a catalytically inactive mutant. Moreover, SIRT2 silencing restored the resistance to axonal degeneration in resveratrol-treated Wld(S) neurons. These results suggest that resveratrol abolishes the resistance of Wld(S) mice to axonal degeneration by enhancing SIRT2-mediated tubulin deacetylation.

UI MeSH Term Description Entries
D008810 Mice, Inbred C57BL One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases. Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008822 Mice, Transgenic Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN. Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D008870 Microtubules Slender, cylindrical filaments found in the cytoskeleton of plant and animal cells. They are composed of the protein TUBULIN and are influenced by TUBULIN MODULATORS. Microtubule
D002478 Cells, Cultured Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others. Cultured Cells,Cell, Cultured,Cultured Cell
D004351 Drug Resistance Diminished or failed response of an organism, disease or tissue to the intended effectiveness of a chemical or drug. It should be differentiated from DRUG TOLERANCE which is the progressive diminution of the susceptibility of a human or animal to the effects of a drug, as a result of continued administration. Resistance, Drug
D004789 Enzyme Activation Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme. Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077185 Resveratrol A stilbene and non-flavonoid polyphenol produced by various plants including grapes and blueberries. It has anti-oxidant, anti-inflammatory, cardioprotective, anti-mutagenic, and anti-carcinogenic properties. It also inhibits platelet aggregation and the activity of several DNA HELICASES in vitro. 3,4',5-Stilbenetriol,3,4',5-Trihydroxystilbene,3,5,4'-Trihydroxystilbene,Resveratrol, (Z)-,Resveratrol-3-sulfate,SRT 501,SRT-501,SRT501,cis-Resveratrol,trans-Resveratrol,trans-Resveratrol-3-O-sulfate,Resveratrol 3 sulfate,cis Resveratrol,trans Resveratrol,trans Resveratrol 3 O sulfate
D000107 Acetylation Formation of an acetyl derivative. (Stedman, 25th ed) Acetylations
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

Related Publications

Kazuhiko Suzuki, and Tatsuro Koike
February 2005, Brain : a journal of neurology,
Kazuhiko Suzuki, and Tatsuro Koike
February 2003, Molecular cell,
Kazuhiko Suzuki, and Tatsuro Koike
August 2011, The European journal of neuroscience,
Kazuhiko Suzuki, and Tatsuro Koike
August 1998, Proceedings of the National Academy of Sciences of the United States of America,
Kazuhiko Suzuki, and Tatsuro Koike
January 2014, Experimental neurology,
Kazuhiko Suzuki, and Tatsuro Koike
July 1995, The European journal of neuroscience,
Kazuhiko Suzuki, and Tatsuro Koike
December 2009, BMC neuroscience,
Copied contents to your clipboard!