setting-up-an-vitro-model-rat-blood-brain-barrier-bbb-focus-on-bbb

Setting-up an <em>In Vitro</em> Model of Rat Blood-brain Barrier (BBB): A Focus on BBB Impermeability and Receptor-mediated Transport

The blood brain barrier (BBB) specifically regulates molecular and cellular flux between the blood and the nervous tissue. Our aim was to develop and ...

CNRS, NICN UMR 7259

Sirtuin1 (Sirt1) is an NAD(+)-dependent deacetylase involved in development, cell survival, stress resistance, energy metabolism, and aging. It is expressed in the mammalian central nervous system (CNS) and is activated during processes associated with neuroprotection. The retinal degeneration 10 (rd10) mouse model of retinitis pigmentosa (RP) was used to investigate the possible role of Sirt1 in this type of retinal degeneration.

Sirt1 involvement in rd10 mouse retinal degeneration.

To evaluate functional and ultrastructural changes in the retina of scavenger receptor B1 (SR-BI) knockout (KO) mice consuming a high fat cholate (HFC) diet.

Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet.

The retina is highly exposed to oxidative stress due to the high level of oxygen consumption in this tissue and its exposure to light. The main DNA base lesion generated by oxygen free radicals is 8-oxoguanine (8-oxoG). However, its presence in retinal cells and the mechanisms underlying its repair remain undetermined.

Expression of 8-oxoguanine DNA glycosylase (Ogg1) in mouse retina.

Replication of positive-strand RNA viruses, the largest group of plant viruses, is initiated by viral RNA-dependent RNA polymerase (RdRp). Given its essential function in viral replication, understanding the regulation of RdRp is of great importance. Here, we show that Turnip yellow mosaic virus (TYMV) RdRp (termed 66K) is degraded by the proteasome at late time points during viral infection and that the accumulation level of 66K affects viral RNA replication in infected Arabidopsis thaliana cells. We mapped the cis-determinants responsible for 66K degradation within its N-terminal noncatalytic domain, but we conclude that 66K is not a natural N-end rule substrate. Instead, we show that a proposed PEST sequence within 66K functions as a transferable degradation motif. In addition, several Lys residues that constitute target sites for ubiquitylation were mapped; mutation of these Lys residues leads to stabilization of 66K. Altogether, these results demonstrate that TYMV RdRp is a target of the ubiquitin-proteasome system in plant cells and support the idea that proteasomal degradation may constitute yet another fundamental level of regulation of viral replication.

The ubiquitin-proteasome system regulates the accumulation of Turnip yellow mosaic virus RNA-dependent RNA polymerase during viral infection.

To describe genetic and clinical findings in a French family affected by best vitelliform macular dystrophy (BVMD).

Article	Year
Sirt1 involvement in rd10 mouse retinal degeneration. Investigative ophthalmology & visual science\| PubMed ID: 19407027	2009
Morphologic and electroretinographic phenotype of SR-BI knockout mice after a long-term atherogenic diet. Investigative ophthalmology & visual science\| PubMed ID: 19420333	2009
Expression of 8-oxoguanine DNA glycosylase (Ogg1) in mouse retina. Molecular vision\| PubMed ID: 19503746	2009
The ubiquitin-proteasome system regulates the accumulation of Turnip yellow mosaic virus RNA-dependent RNA polymerase during viral infection. The Plant cell\| PubMed ID: 20823192	2010
Phenotypic variability in a French family with a novel mutation in the BEST1 gene causing multifocal best vitelliform macular dystrophy. Molecular vision\| PubMed ID: 21293734	2011

Emmanuelle Lacassagne

Biography

JoVE Journal Publications

Other Publications