A novel Rac1-GSPT1 signaling pathway controls astrogliosis following central nervous system injury

Astrogliosis (i.e. glial scar), which is comprised primarily of proliferated astrocytes at the lesion site and migrated astrocytes from neighboring regions, is one of the key reactions in determining outcomes after CNS injury. In an effort to identify potential molecules/pathways that regulate astrogliosis, we sought to determine whether Rac/Rac-mediated signaling in astrocytes represents a novel candidate for therapeutic intervention following CNS injury. For these studies, we generated mice with Rac1 deletion under the control of the GFAP (glial fibrillary acidic protein) promoter (GFAP-Cre;Rac1(flox/flox)). GFAP-Cre;Rac1(flox/flox) (Rac1-KO) mice exhibited better recovery after spinal cord injury and exhibited reduced astrogliosis at the lesion site relative to control. Reduced astrogliosis was also observed in Rac1-KO mice following microbeam irradiation-induced injury. Moreover, knockdown (KD) or KO of Rac1 in astrocytes (LN229 cells, primary astrocytes, or primary astrocytes from Rac1-KO mice) led to delayed cell cycle progression and reduced cell migration. Rac1-KD or Rac1-KO astrocytes additionally had decreased levels of GSPT1 (G(1) to S phase transition 1) expression and reduced responses of IL-1β and GSPT1 to LPS treatment, indicating that IL-1β and GSPT1 are downstream molecules of Rac1 associated with inflammatory condition. Furthermore, GSPT1-KD astrocytes had cell cycle delay, with no effect on cell migration. The cell cycle delay induced by Rac1-KD was rescued by overexpression of GSPT1. Based on these results, we propose that Rac1-GSPT1 represents a novel signaling axis in astrocytes that accelerates proliferation in response to inflammation, which is one important factor in the development of astrogliosis/glial scar following CNS injury

8.4 エネルギー代謝異常と老化

エネルギー代謝異常と老化石井直明［東海大学医学部分子生命科学］＊所属は当時のものを記

Isolation of Oligotrophic Denitrifiers Carrying Previously Uncharacterized Functional Gene Sequences▿ †

Oligotrophic denitrifying bacteria, including those belonging to the genera Herbaspirillum, Azospirillum, and Bradyrhizobium, were obtained using a single-cell isolation technique. The taxonomic composition of the denitrifier population was similar to those assessed by previous culture-independent studies. The sequencing of nitrite reductase and N2O reductase genes of these strains revealed previously unknown links between 16S rRNA and the denitrification-functional gene phylogenies. In particular, we identified Bradyrhizobium strains that harbor nirS sequences previously detected only in culture-independent studies

Relationship Between Catalase and Life Span in Recombinant Inbred Strains of Caenorhabditis elegans

Johnson and Wood constructed recombinant inbred strains of Caenorhabditis elegans with life spans ranging from 10 to 31 days. Using these strains, we have demonstrated previously that hyperoxia and methyl viologen inhibited development at rates inversely correlated with life span. The growth rates of the short-lived recombinant inbred strains were more profoundly inhibited by oxidative stress than were those of the long-lived strains. Here we report a positive correlation between life span and catalase levels in these same strains. Specifically, when compared to short-lived strains at 10 days after fertilization, the long-lived strains possessed higher levels of total enzymatic catalase. Northern blots indicated a similar relationship between life span and clt-1mRNA (the cytosolic catalase). This suggests that at least some of the polygenes that influence life span are also responsible for regulating gene expression of catalase, an important defense component against oxidative stress

Recent deceleration of oceanic pCO2 increase in the western North Pacific in winter

Recent changes in oceanic CO2 partial pressure (pCO2^[sea]) have attracted increasing interest as they relate to the increase in atmospheric CO2 and climate change. We report decadal changes in the growth rates of pCO2^[sea] in latitudinal zones from 3°N to 33°N along the repeat hydrographic line at 137°E in the western North Pacific in winter. The growth rates of pCO2^[sea] for 1999-2009 (-0.3 ± 0.9 [mean ± 1σ] to 1.7 ± 0.5 μatm yr^[-1]) were lower than those for 1984-1997 (0.7 ± 0.3 to 2.2 ± 0.6 μatm yr^[-1]) at most latitudes, indicative of the recent notable deceleration of pCO2^[sea] increase. For latitudes around 10-20°N, we attribute the reduction in the growth rate of pCO2^[sea] for 1999-2009 primarily to the reduction in the contribution from dissolved inorganic carbon (DIC) originating from a reduction in carbon accumulation associated with the expansion of the western Subtropical Gyre towards the south