Characterization of LPS and interferon-γ triggered activation-induced cell death in N9 and primary microglial cells: induction of the mitochondrial gateway by nitric oxide

Mayo, Lior; Stein, Reuven

doi:10.1038/sj.cdd.4401989

Cited by 33 publications

(43 citation statements)

References 11 publications

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“…We used the N9 16 murine microglia cell line, maintained in a Roswell Park Memorial Institute (RPMI) supplement containing L-Glut (Biological INTD 01-100-1A) with an additional 10% heat-inactivated fetal bovine serum (Biological INTD 04-127-1A) and 1% Pen-Strep (Biological INTD 03-032-1B) in 5% CO 2 atmosphere at 37 C.…”

Section: Cell Culturesmentioning

confidence: 99%

γ‐Secretase component presenilin is important for microglia β‐amyloid clearance

Farfara

Trudler

Segev-Amzaleg

et al. 2010

Annals of Neurology

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We suggest for the first time, a dual role for γ-secretase in Alzheimer's disease. One role is the cleavage of the amyloid precursor protein for pathologic β-amyloid production and the other is to regulate microglia activity that is important for clearing neurotoxic β-amyloid deposits. Further studies of γ-secretase-mediated cellular pathways in microglia may provide useful insights into the development of Alzheimer's disease and other neurodegenerative diseases, providing future avenues for therapeutic intervention.

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Section: Cell Culturesmentioning

confidence: 99%

γ‐Secretase component presenilin is important for microglia β‐amyloid clearance

Farfara

Trudler

Segev-Amzaleg

et al. 2010

Annals of Neurology

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“…To determine cell viability, we used the standard 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT; Sigma) test, with the slight modifications suggested by Mayo and Stein [42]. SHSY5Y cells were seeded on a 96-well plate at a concentration of 10 5 cells per well with or without exposure to glycated Tau40 (3-day incubation) at various concentrations for 8 h. After 24 or 48 h, MTT (final concentration 0.5 mg/ml) was added and plates were incubated at 37°C for 4 h. The reaction was stopped by replacement of the MTT-containing medium with 150 ll dimethysulfoxide, and absorbance at 540 nm was measured on a Multiscan MK3 spectrophotometer (Thermo Electron Corporation, USA).…”

Section: Cell Viability Testmentioning

confidence: 99%

d-Ribosylated Tau forms globular aggregates with high cytotoxicity

Chen

Wei

Wang

et al. 2009

Cell. Mol. Life Sci.

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Although the glycation of Tau that is involved in paired helical filament formation in Alzheimer's disease has been widely studied, little attention has been paid to the role of D-ribose in the glycation of Tau. Here, we show that Tau is rapidly glycated in the presence of D-ribose, resulting in oligomerization and polymerization. Glycated derivatives appeared after 24 h incubation. Western blotting indicated the formation of advanced glycation end-products (AGEs) during initial stages of glycation. Thioflavin T-positive (ThT-positive) aggregations that appeared from day 4 indicated the globular-like features. Atomic force microscopy revealed that the surface morphology of ribosylated Tau40 was globular-like. Kinetic studies suggested that D-ribosylated Tau is slowly oligomerized and rapidly polymerized with ThT-positive features. Moreover, D-ribosylated Tau aggregates were highly toxic to SHSY5Y cells and resulted in both apoptosis and necrosis. This work has demonstrated that D-ribose reacted with Tau protein rapidly, producing ThT-positive aggregations which had high cytotoxicity.

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“…Microglial activation was therefore postulated to contribute to the pathogenesis of several neurodegenerative diseases, such as Alzheimer's and Parkinson's (Kim and Joh, 2006;Streit, 2004). Like other cells in the hematopoietic system, activated microglia can be eliminated by microglial activation-induced cell death, in which caspases and Bcl-2 family proteins (Dihne et al, 2001;Lee et al, 2001;Mayo and Stein, 2007;Vela et al, 2002) such as Bid (Mayo and Stein, 2007) play a role. It is not yet known whether the core apoptotic proteins can also regulate microglial nonapoptotic functions.…”

Section: Introductionmentioning

confidence: 97%

Bid regulates the immunological profile of murine microglia and macrophages

Mayo

Levy

Jacob‐Hirsch

et al. 2010

Glia

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Apoptosis is a controlled cell-death process mediated inter alia by proteins of the Bcl-2 family. Some proteins previously shown to promote the apoptotic process were found to have nonapoptotic functions as well. Microglia, the resident immune cells of the central nervous system, respond to brain derangements by becoming activated to contend with the brain damage. Activated microglia can also undergo activation-induced cell death. Previous studies have addressed the role of core apoptotic proteins in the death process, but whether these proteins also play a role or not in the activation process is not been reported. Here we explore the effect of the BH3-only protein Bid on the immunological features of microglia and macrophages. Our results showed that Bid regulates both the phagocytotic activities and the inflammatory profiles of these cells. Deficiency of Bid attenuated the phagocytotic activity of primary microglia and peritoneal macrophages. It also changed the expression profile of distinct inflammation-related genes in lipopolysaccharide-activated microglia and peritoneal macrophages in vitro and in an in vivo sepsis-like paradigm. Notably, similar changes followed downregulation of Bid in the N9 microglial cell line. Cell death could not be detected in any of the systems examined. Our findings demonstrate that Bid can regulate the immunological profiles of activated microglial and macrophages, via a novel nonapoptotic activity. In view of the critical role of these cells in various pathologies, including acute and chronic brain insults, our findings suggest that impairments in Bid expression may contribute to these pathologies also via a nonapoptotic activity.

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Characterization of LPS and interferon-γ triggered activation-induced cell death in N9 and primary microglial cells: induction of the mitochondrial gateway by nitric oxide

Cited by 33 publications

References 11 publications

γ‐Secretase component presenilin is important for microglia β‐amyloid clearance

γ‐Secretase component presenilin is important for microglia β‐amyloid clearance

d-Ribosylated Tau forms globular aggregates with high cytotoxicity

Bid regulates the immunological profile of murine microglia and macrophages

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