Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from Apoptosis after serum withdrawal

Sciatic nerve (SN) transection-induced apoptosis of dorsal root ganglion neurons (DRGN) is one factor determining the efficacy of peripheral axonal regeneration and the return of sensation. Here, we tested the hypothesis that caspase-2(CASP2) orchestrates apoptosis of axotomised DRGN both in vivo and in vitro by disrupting the local neurotrophic supply to DRGN. We observed significantly elevated levels of cleaved CASP2 (C-CASP2), compared to cleaved caspase-3 (C-CASP3), within TUNEL+DRGN and DRG glia (satellite and Schwann cells) after SN transection. A serum withdrawal cell culture model, which induced 40% apoptotic death in DRGN and 60% in glia, was used to model DRGN loss after neurotrophic factor withdrawal. Elevated C-CASP2 and TUNEL were observed in both DRGN and DRG glia, with C-CASP2 localisation shifting from the cytosol to the nucleus, a required step for induction of direct CASP2-mediated apoptosis. Furthermore, siRNAmediated downregulation of CASP2 protected 50% of DRGN from apoptosis after serum withdrawal, while downregulation of CASP3 had no effect on DRGN or DRG glia survival. We conclude that CASP2 orchestrates the death of SN-axotomised DRGN directly and also indirectly through loss of DRG glia and their local neurotrophic factor support. Accordingly, inhibiting CASP2 expression is a potential therapy for improving both the SN regeneration response and peripheral sensory recovery

Eukaryote DIRS1-like retrotransposons: an overview

<p>Abstract</p> <p>Background</p> <p>DIRS1-like elements compose one superfamily of tyrosine recombinase-encoding retrotransposons. They have been previously reported in only a few diverse eukaryote species, describing a patchy distribution, and little is known about their origin and dynamics. Recently, we have shown that these retrotransposons are common among decapods, which calls into question the distribution of DIRS1-like retrotransposons among eukaryotes.</p> <p>Results</p> <p>To determine the distribution of DIRS1-like retrotransposons, we developed a new computational tool, ReDoSt, which allows us to identify well-conserved DIRS1-like elements. By screening 274 completely sequenced genomes, we identified more than 4000 DIRS1-like copies distributed among 30 diverse species which can be clustered into roughly 300 families. While the diversity in most species appears restricted to a low copy number, a few bursts of transposition are strongly suggested in certain species, such as <it>Danio rerio </it>and <it>Saccoglossus kowalevskii</it>.</p> <p>Conclusion</p> <p>In this study, we report 14 new species and 8 new higher taxa that were not previously known to harbor DIRS1-like retrotransposons. Now reported in 61 species, these elements appear widely distributed among eukaryotes, even if they remain undetected in streptophytes and mammals. Especially in unikonts, a broad range of taxa from Cnidaria to Sauropsida harbors such elements. Both the distribution and the similarities between the DIRS1-like element phylogeny and conventional phylogenies of the host species suggest that DIRS1-like retrotransposons emerged early during the radiation of eukaryotes.</p