The 18 kDa mitochondrial translocator protein (TSPO) prevents accumulation of protoporphyrin IX. Involvement of reactive oxygen species (ROS).

By exposing cells of the U118MG glioblastoma cell line to protoporphyrin IX (PPIX) in culture, we found that the 18 kDa mitochondrial translocator protein (TSPO) prevents intracellular accumulation of PPIX. In particular, TSPO knockdown by stable transfection of TSPO silencing siRNA vectors into U118MG cells leads to mitochondrial PPIX accumulation. In combination with light exposure, the PPIX accumulation led to cell death of the TSPO knockdown cells. In the sham control cells (stable transfection of scrambled siRNA vectors), TSPO expression remained high and no PPIX accumulation was observed. The prevention of PPIX accumulation by TSPO was not due to conversion of PPIX to heme in the sham control cells. Similar to TSPO knockdown, the reactive oxygen species (ROS) scavenger glutathione (GSH) also enhanced PPIX accumulation. This suggests that that ROS generation as modulated by TSPO activation may present a mechanism to prevent accumulation of PPIX.

A caspase-3-cleaved fragment of the glial glutamate transporter EAAT2 is sumoylated and targeted to promyelocytic leukemia nuclear bodies in mutant SOD1-linked amyotrophic lateral sclerosis.

EAAT2 (excitatory amino acid transporter 2) is a high affinity, Na+-dependent glutamate transporter of glial origin that is essential for the clearance of synaptically released glutamate and prevention of excitotoxicity. During the course of human amyotrophic lateral sclerosis (ALS) and in a transgenic mutant SOD1 mouse model of the disease, expression and activity of EAAT2 is remarkably reduced. We previously showed that some of the mutant SOD1 proteins exposed to oxidative stress inhibit EAAT2 by triggering caspase-3 cleavage of EAAT2 at a single defined locus. This gives rise to two fragments that we termed truncated EAAT2 and COOH terminus of EAAT2 (CTE). In this study, we report that analysis of spinal cord homogenates prepared from mutant G93A-SOD1 mice reveals CTE to be of a higher molecular weight than expected because it is conjugated with SUMO-1. The sumoylated CTE fragment (CTE-SUMO-1) accumulates in the spinal cord of these mice as early as presymptomatic stage (70 days of age) and not in other central nervous system areas unaffected by the disease. The presence and accumulation of CTE-SUMO-1 is specific to ALS mice, since it does not occur in the R6/2 mouse model for Huntington disease. Furthermore, using an astroglial cell line, primary culture of astrocytes, and tissue samples from G93A-SOD1 mice, we show that CTE-SUMO-1 is targeted to promyelocytic leukemia nuclear bodies. Since one of the proposed functions of promyelocytic leukemia nuclear bodies is regulation of gene transcription, we suggest a possible novel mechanism by which the glial glutamate transporter EAAT2 could contribute to the pathology of ALS.

Infection rates after 3175 total hip and total knee replacements performed with and without a horizontal unidirectional filtered air-flow system.

To determine the effect of the ventilation system on infection rates after total hip and total knee arthroplasties performed in operating rooms with and without a horizontal unidirectional filtered air-flow system, using modern antiseptic conditions and antibiotic prophylaxis, all of the single-stage procedures (3175 of a total of 4769) were subjected to statistical analysis and fifty-seven matched pairs for controls were established. A reduced infection rate after total hip replacement (from 1.4 to 0.9 per cent) and an increased infection rate after total knee replacement (from 1.4 to 3.9 per cent) were found when patients operated on in the filtered laminar air-flow operating room were compared with those whose operations were done in two conventional rooms. This pattern was statistically significant and was believed to be due to the positions of the operating team and of the wound with respect to the air flow. Prospectively accumulated factors (such as the experience of the surgeon, the duration of surgery, the diagnosis, and the patient's age) as well as retrospectively accumulated factors (such as predisposing conditions of the patient) did not explain the observed patterns of infection.

Joint looseness: a function of the person and the joint.

In order to evaluate whether joint-looseness is a function of a particular joint and/or a characteristic of the person (a trait), 124 male and female subjects varying in age from 6 to 18 were tested. Evidence was found that joint-looseness is a trait. The validity of the trait measure was enhanced by finding significant negative correlations with age and performance. Although females were significantly looser on some joint-looseness tests, they were not looser on the trait indicator.