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Autophagic Activities (autophagic + activity)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Productive Chlamydia trachomatis lymphogranuloma venereum 434 infection in cells with augmented or inactivated autophagic activities

FEMS MICROBIOLOGY LETTERS, Issue 2 2009
Niseema Pachikara
Abstract Autophagy, a eukaryotic cellular activity leading to the degradation of cellular components, serves as a defense mechanism against facultative intracellular bacteria as well as a growth niche for the obligate intracellular bacterium Coxiella burnetii. We here demonstrate that the obligate intracellular bacterial pathogen Chlamydia trachomatis lymphogranuloma venereum strongly induced autophagy in the middle of the chlamydial developmental cycle (24 h after infection), a time point with maximal level of chlamydial replication, but not during the early stages with low overall chlamydial metabolism (before 8 h). No autophagy induction was evident in cells exposed to heat- and UV-inactivated elementary bodies (EBs, the infectious form of Chlamydia) or to inocula from which EBs had been removed before inoculation. Blocking chlamydial development with chloramphenicol also prevented autophagy induction in cells infected with infectious EBs. It appears that autophagy is activated primarily in response to the metabolic stress consequent to chlamydial replication. However, autophagy-defective ATG5,/, cells supported chlamydial development as efficiently as autophagy-proficient ATG5+/+ cells. [source]

Postischemic treatment of neonatal cerebral ischemia should target autophagy,

ANNALS OF NEUROLOGY, Issue 3 2009
Julien Puyal PhD
Objective To evaluate the contributions of autophagic, necrotic, and apoptotic cell death mechanisms after neonatal cerebral ischemia and hence define the most appropriate neuroprotective approach for postischemic therapy. Methods Rats were exposed to transient focal cerebral ischemia on postnatal day 12. Some rats were treated by postischemic administration of pan-caspase or autophagy inhibitors. The ischemic brain tissue was studied histologically, biochemically, and ultrastructurally for autophagic, apoptotic, and necrotic markers. Results Lysosomal and autophagic activities were increased in neurons in the ischemic area from 6 to 24 hours postinjury, as shown by immunohistochemistry against lysosomal-associated membrane protein 1 and cathepsin D, by acid phosphatase histochemistry, by increased expression of autophagosome-specific LC3-II and by punctate LC3 staining. Electron microscopy confirmed the presence of large autolysosomes and putative autophagosomes in neurons. The increases in lysosomal activity and autophagosome formation together demonstrate increased autophagy, which occurred mainly in the border of the lesion, suggesting its involvement in delayed cell death. We also provide evidence for necrosis near the center of the lesion and apoptotic-like cell death in its border, but in nonautophagic cells. Postischemic intracerebroventricular injections of autophagy inhibitor 3-methyladenine strongly reduced the lesion volume (by 46%) even when given >4 hours after the beginning of the ischemia, whereas pan-caspase inhibitors, carbobenzoxy-valyl-alanyl-aspartyl(OMe)-fluoromethylketone and quinoline-val-asp(OMe)-Ch2-O-phenoxy, provided no protection. Interpretation The prominence of autophagic neuronal death in the ischemic penumbra and the neuroprotective efficacy of postischemic autophagy inhibition indicate that autophagy should be a primary target in the treatment of neonatal cerebral ischemia. Ann Neurol 2009 [source]

Autophagic pathways and metabolic stress

DIABETES OBESITY & METABOLISM, Issue 2010
S. Kaushik
Autophagy is an essential intracellular process that mediates degradation of intracellular proteins and organelles in lysosomes. Autophagy was initially identified for its role as alternative source of energy when nutrients are scarce but, in recent years, a previously unknown role for this degradative pathway in the cellular response to stress has gained considerable attention. In this review, we focus on the novel findings linking autophagic function with metabolic stress resulting either from proteins or lipids. Proper autophagic activity is required in the cellular defense against proteotoxicity arising in the cytosol and also in the endoplasmic reticulum, where a vast amount of proteins are synthesized and folded. In addition, autophagy contributes to mobilization of intracellular lipid stores and may be central to lipid metabolism in certain cellular conditions. In this review, we focus on the interrelation between autophagy and different types of metabolic stress, specifically the stress resulting from the presence of misbehaving proteins within the cytosol or in the endoplasmic reticulum and the stress following a lipogenic challenge. We also comment on the consequences that chronic exposure to these metabolic stressors could have on autophagic function and on how this effect may underlie the basis of some common metabolic disorders. [source]

2232: Why are retinal pigment epithelial cells so resistant to oxidative stress?

ACTA OPHTHALMOLOGICA, Issue 2010
U BRUNK
Purpose The functional integrity of postmitotic retinal pigment epithelial (RPE) cells is crucial for photoreceptor survival, and RPE malfunction is considered an important factor behind age-related macular degeneration (AMD). Although RPE cells daily phagocytose large amounts of fatty acid-rich distal photoreceptor material, their lysosomal accumulation of lipofuscin (LF) is nevertheless slow. Only late in life do humans have LF-loaded RPE cells, which then not only have a reduced capacity to endocytose photoreceptor material but also are less capable of keeping up with normal autophagy. The latter activity is important for normal turnover of the cell's own components. Methods ARPE-19 cells in culture were evaluated with respect to lysosomal stability at oxidative stress. Redox-active iron, autophagic activity (evaluation of LC3-I and LC3-II protein), and anti-oxidative proteins were assayed using cytochemistry (Sulphide-Silver Method), electron spin resonance (ESR) and western blotting for a variety of stress proteins. Results The lysosomal compartment of the ARPE-19 cells was found remarkably resistant to oxidative stress. The SSM and ESR methods suggested low lysosomal amounts of redox-active iron and no enhanced autophagy following oxidative stress. The normal autophagy rate was higher than in other professional scavengers. Conclusion The found low amount of lysosomal redox-active iron explains the slow formation of lipofuscin over time and the remarkable stability that ARPE-19 cells and their lysosomes show even under severe oxidative stress. The molecular mechanisms behind this phenomenon may be an unusual capacity to quickly export low mass iron from lysosomes to the cytosol and/or a high normal degree of autophagy of iron-binding stress proteins. [source]