Ctly result from the induction of amyloidogenesis by neuroinflammation. Noble et al. reported that acute systemic inflammation induces central mitochondrial damage and amnesic deficit in adult Swiss mice [47]. Sparkman [17], and Milatovic et al. [48] and Szczepanik and Ringheim [49] reported that intraperitoneal injections of LPS cause AD-like neuronal degeneration. We have also found that mutant presenilin 2 (a genetic AD model) mice brains showed increased inflammation and accumulation of Ag accompanied by an increase of apoptotic neuronal cell death. LPS induced neuro-inflammatory signal activation (Cox-2 and ERK activation) could be involved in the LPSinduced neuronal cell death. Jang and Surh showed that beta-amyloid-induced apoptosis is associated with cyclooxygenase-2 up-regulation through activation of NFB, which is mediated by upstream kinases including ERK and p38 MAPK [50]. We also previously demonstrated that Bcl-2 overexpression protects neuronal cells against A-induced cell death in differentiated PC12, and its protective effect was related to the reduction of A-induced activation of p38 MAP kinase [51]. Even though the exact signal pathways in the LPS-induced neuronal cell death and amyloidogenesis are not clear, the increase of apoptotic neuronal cell death via the elevation of A12 could be an important mechanism in LPS-induced memory impairment. The activation of astrocytes by treatment with LPS may induce several cytotoxic cytokines which could also hurt neighboring neuronal cells via directly killing mechanisms [52-54] or via elevation of A12 [9,10]. In conclusion, systemic inflammation by treatment with LPS causes elevation of amyloidogenesis and neuronal cell death which finally result in memory impairment.Authors’ contributionsJWL performed behavioral tests and some of ELISA assay, and performed western blotting, performed some of the statistical analyses, and prepared and wrote the manuscript. YKL performed the immunohistochemical staining, assessment of neuronal complement immunoreactivity, and helped to write the manuscript. DYC performed the immunohistochemical evaluation and reviewed the manuscript. DYY assisted with the data collection, was involved in the experimental design, and wrote and reviewed the manuscript. SBB and KWO assisted with the manuscript preparation, and discussed the behavioral and biochemical changes.Phenytoin JTH designed the studies, reviewed the data, and wrote the manuscript.Bicuculline All authors read and approved the final manuscript.PMID:23991096 Acknowledgements”This work was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD)” (The Regional Research Universities Program/Chungbuk BIT Research-Oriented University Consortium).
THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 288, NO. 36, pp. 259956003, September 6, 2013 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A.Negative Elongation Factor (NELF) Coordinates RNA Polymerase II Pausing, Premature Termination, and Chromatin Remodeling to Regulate HIV Transcription*Received for publication, June 24, 2013, and in revised form, July 23, 2013 Published, JBC Papers in Press, July 24, 2013, DOI 10.1074/jbc.M113.Malini Natarajan,2, Gillian M. Schiralli Lester, Chanhyo Lee Anamika Missra Gregory A. Wasserman , Martin Steffen**, David. S. Gilmour and Andrew J. Henderson3 From the Immunology and Infectious Diseases, Integrated Biosciences Graduate Program, Penn State University, University Park, Pe.
