Reactive oxygen species‐induced cell death of rat primary astrocytes through mitochondria‐mediated mechanism

Astrocytes, the most abundant glial cell population in the central nervous system (CNS), play physiological roles in neuronal activities. Oxidative insult induced by the injury to the CNS causes neural cell death through extrinsic and intrinsic pathways. This study reports that reactive oxygen species (ROS) generated by exposure to the strong oxidizing agent, hexavalent chromium (Cr(VI)) as a chemical‐induced oxidative stress model, caused astrocytes to undergo an apoptosis‐like cell death through a caspase‐3‐independent mechanism. Although activating protein‐1 (AP‐1) and NF‐κB were activated in Cr(VI)‐primed astrocytes, the inhibition of their activity failed to increase astrocytic cell survival. The results further indicated that the reduction in mitochondrial membrane potential (MMP) was accompanied by an increase in the levels of ROS in Cr(VI)‐primed astrocytes. Moreover, pretreatment of astrocytes with N‐acetylcysteine (NAC), the potent ROS scavenger, attenuated ROS production and MMP loss in Cr(VI)‐primed astrocytes, and significantly increased the survival of astrocytes, implying that the elevated ROS disrupted the mitochondrial function to result in the reduction of astrocytic cell viability. In addition, the nuclear expression of apoptosis‐inducing factor (AIF) and endonuclease G (EndoG) was observed in Cr(VI)‐primed astrocytes. Taken together, evidence shows that astrocytic cell death occurs by ROS‐induced oxidative insult through a caspase‐3‐independent apoptotic mechanism involving the loss of MMP and an increase in the nuclear levels of mitochondrial pro‐apoptosis proteins (AIF/EndoG). This mitochondria‐mediated but caspase‐3‐independent apoptotic pathway may be involved in oxidative stress‐induced astrocytic cell death in the injured CNS. J. Cell. Biochem. 107: 933–943, 2009. © 2009 Wiley‐Liss, Inc.     

Microglial phagocytosis attenuated by short-term exposure to exogenous ATP through P2X7 receptor action

Microglia, the CNS resident macrophages responsible for the clearance of degenerating cellular fragments, are essential to tissue remodeling and repair after CNS injury. ATP can be released in large amounts after CNS injury and may mediate microglial activity through the ionotropic P2X and the metabotropic P2Y receptors. This study indicates that exposure to a high concentration of ATP for 30 min rapidly induces changes of the microglial cytoskeleton, and significantly attenuates microglial phagocytosis. A pharmacological approach showed that ATP-induced inhibition of microglial phagocytotic activity was due to P2X₇R activation, rather than that of P2YR. Activation of P2X₇R by its agonist, 2'-3'- O -(4-benzoyl)benzoyl-ATP (BzATP), produced a Ca²⁺-independent reduction in microglial phagocytotic activity. In addition, the knockdown of P2X₇R expression by lentiviral-mediated shRNA interference or the blockade of P2X₇R activation by the specific antagonists, oxidized ATP (oxATP) and brilliant blue G, has efficiently restored the phagocytotic activity of ATP and BzATP-treated microglia. Our results reveal that P2X₇R activation may induce the formation of a Ca²⁺-independent signaling complex, which results in the reduction of microglial phagocytosis. This suggests that exposure to ATP for a short-term period may cause insufficient clearance of tissue debris by microglia through P2X₇R activation after CNS injury, and that blockade of this receptor may preserve the phagocytosis of microglia and facilitate CNS tissue repair.     

Modelling the growth of Japanese eel Anguilla japonica in the lower reach of the Kao-Ping River, southern Taiwan: an information theory approach

Information theory was applied to select the best model fitting total length ( L _T)-at-age data and calculate the averaged model for Japanese eel Anguilla japonica compiled from published literature and the differences in growth between sexes were examined. Five candidate growth models were the von Bertalanffy, generalized von Bertalanffy, Gompertz, logistic and power models. The von Bertalanffy growth model with sex-specific coefficients was best supported by the data and nearly overlapped the averaged growth model based on Akaike weights, indicating a similar fit to the data. The Gompertz, generalized von Bertalanffy and power growth models were also substantially supported by the data. The L _T at age of A. japonica were larger in females than in males according to the averaged growth mode, suggesting a sexual dimorphism in growth. Model inferences based on information theory, which deal with uncertainty in model selection and robust parameter estimates, are recommended for modelling the growth of A. japonica .     

Neural progenitors isolated from newborn rat spinal cords differentiate into neurons and astroglia

Permanent functional deficit in patients with spinal cord injury (SCI) is in part due to severe neural cell death. Therefore, cell replacement using stem cells and neural progenitors that give rise to neurons and glia is thought to be a potent strategy to promote tissue repair after SCI. Many studies have shown that stem cells and neural progenitors can be isolated from embryonic, postnatal and adult spinal cords. Recently, we isolated neural progenitors from newborn rat spinal cords. In general, the neural progenitors grew as spheres in culture, and showed immunoreactivity to a neural progenitor cellular marker, nestin. They were found to proliferate and differentiate into glial fibrillary acidic protein-positive astroglia and multiple neuronal populations, including GABAergic and cholinergic neurons. Neurotrophin 3 and neurotrophin 4 enhanced the differentiation of neural progenitors into neurons. Furthermore, the neural progenitors that were transplanted into contusive spinal cords were found to survive and have migrated in the spinal cord rostrally and caudally over 8 mm to the lesion center 7 days after injury. Thus, the neural progenitors isolated from newborn rat spinal cords in combination with neurotrophic factors may provide a tool for cell therapy in SCI patients.     

RNA and β-Hemolysin of Group B Streptococcus Induce Interleukin-1β (IL-1β) by Activating NLRP3 Inflammasomes in Mouse Macrophages

The inflammatory cytokine IL-1β is critical for host responses against many human pathogens. Here, we define Group B Streptococcus (GBS)-mediated activation of the Nod-like receptor-P3 (NLRP3) inflammasome in macrophages. NLRP3 activation requires GBS expression of the cytolytic toxin, β-hemolysin, lysosomal acidification, and leakage. These processes allow the interaction of GBS RNA with cytosolic NLRP3. The present study supports a model in which GBS RNA, along with lysosomal components including cathepsins, leaks out of lysosomes and interacts with NLRP3 to induce IL-1β production.     

Wrinkling instabilities for biologically relevant fiber-reinforced composite materials with a case study of Neo-Hookean/Ogden–Gasser–Holzapfel bilayer

Biomechanics and Modeling in Mechanobiology - Wrinkling is a ubiquitous surface phenomenon in many biological tissues and is believed to play an important role in arterial health. As arteries are...     

Differences in growth rates among cohorts of Encrasicholina punctifer and Engraulis japonicus larvae in the coastal waters off Tanshui River Estuary, Taiwan, as indicated by otolith microstructure analysis

The hatching dates of Encrasicholina punctifer and Engraulis japonicus larvae collected in the coastal waters off Tanshui River Estuary during the fishing seasons of 1992 and 1993 indicated that these two anchovies had protracted spawning seasons, which resulted in multiple recruitment cohorts. Encrasicholina punctifer larvae recruited to the estuary from October to March, while the majority of E. japonicus larvae came in March-May and to a lesser extent in October and November. The E. punctifer larvae on arrival to the estuary were 17·4–35·6 mm in length, 167ndash;89 days old and had growth rates of 0·4–1·0 mm day⁻¹, E. japonicus larvae were 12·1–32·7 mm in length, 19–62 days old and had growth rates of 0·7–0·9 mm day⁻¹. Growth rates were significantly different among cohorts and positively correlated to water temperature.     

Novel Assay Reveals Multiple Pathways Regulating Stress-Induced Accumulations of Inorganic Polyphosphate in Escherichia coli

A major impediment to understanding the biological roles of inorganic polyphosphate (polyP) has been the lack of sensitive definitive methods to extract and quantitate cellular polyP. We show that polyP recovered in extracts from cells lysed with guanidinium isothiocynate can be bound to silicate glass and quantitatively measured by a two-enzyme assay: polyP is first converted to ATP by polyP kinase, and the ATP is hydrolyzed by luciferase to generate light. This nonradioactive method can detect picomolar amounts of phosphate residues in polyP per milligram of extracted protein. A simplified procedure for preparing polyP synthesized by polyP kinase is also described. Using the new assay, we found that bacteria subjected to nutritional or osmotic stress in a rich medium or to nitrogen exhaustion had large and dynamic accumulations of polyP. By contrast, carbon exhaustion, changes in pH, temperature upshifts, and oxidative stress had no effect on polyP levels. Analysis of Escherichia coli mutants revealed that polyP accumulation depends on several regulatory genes, glnD (NtrC), rpoS, relA, and phoB.