71 research outputs found
Hsp70 and its molecular role in nervous system diseases
Heat shock proteins (HSPs) are induced in response to many injuries including stroke, neurodegenerative disease, epilepsy, and
trauma. The overexpression of one HSP in particular, Hsp70, serves a protective role in several different models of nervous
system injury, but has also been linked to a deleterious role in some diseases. Hsp70 functions as a chaperone and protects
neurons from protein aggregation and toxicity (Parkinson disease, Alzheimer disease, polyglutamine diseases, and amyotrophic
lateral sclerosis), protects cells from apoptosis (Parkinson disease), is a stress marker (temporal lobe epilepsy), protects cells from
inflammation (cerebral ischemic injury), has an adjuvant role in antigen presentation and is involved in the immune response in
autoimmune disease (multiple sclerosis). The worldwide incidence of neurodegenerative diseases is high. As neurodegenerative
diseases disproportionately affect older individuals, disease-related morbidity has increased along with the general increase in
longevity. An understanding of the underlying mechanisms that lead to neurodegeneration is key to identifying methods of
prevention and treatment. Investigators have observed protective effects of HSPs induced by preconditioning, overexpression,
or drugs in a variety of models of brain disease. Experimental data suggest that manipulation of the cellular stress response may
offer strategies to protect the brain during progression of neurodegenerative disease
Stress response in mesoangioblast stem cells
Stem cells are presumed to survive various stresses, since they are recruited to areas of tissue damage and regeneration, where inflammatory cytokines and cytotoxic cells may result in severe cell injury. We explored the ability of mesoangioblasts to respond to different cell stresses such as heat, heavy metals and osmotic stress, by analyzing heat shock protein (HSP)70 synthesis as a stress indicator. We found that the A6 mesoangioblast stem cells constitutively synthesize HSP70 in a heat shock transcription factor (HSF)-independent way. However, A6 respond to heat shock and cadmium treatment by synthesizing HSP70 over the constitutive expression and this synthesis is HSF1 dependent. The exposure of A6 to copper or to a hypertonic medium does neither induce HSP70 synthesis nor activation of HSF1, while a constitutive binding of constitutive heat shock element binding factor was found. Together, these data suggest that mesoangioblasts constitutively express HSP70 as an 'a priori' activation mechanism, while they maintain the ability to respond to stress stimuli. © 2006 Nature Publishing Group. All rights reserved
Rapid changes in heat-shock cognate 70 levels, heat-shock cognate phosphorylation state, heat-shock transcription factor, and metal transcription factor activity levels in response to heavy metal exposure during sea urchin embryonic development.
The aim of the present study was to analyze
and compare the effects of several metals on the embryos
of the sea urchin Paracentrotus lividus, a key species
within the Mediterranean Sea ecosystem. Embryos were
continuously exposed from fertilization to the following
metals: 0.6 mg/l copper, 3 mg/l lead, and 6 mg/l nickel.
The embryos were then monitored for metal responses at
the gastrula stage, which occurred 24 h after exposure. A
biochemical multi-experimental approach was taken and
involved the investigation of the levels of HSC70 expression
and the involvement of heat shock factor (HSF) and/or
metal transcription factor (MTF) in the response. Immunoblotting
assays and electrophoretic mobility shift assays
(EMSA) were used to detect stress protein levels and to
study the interaction between DNA and specific transcription
factors, respectively. In the 1 h during exposure
to heavy metals, changes in HSC70 levels and HSC70 a
phosphorylation state were observed. Rapid changes in
HSF and MTF DNA-binding activity also occurred during
the early stages of heavy metal exposure. In contrast, few
developmental abnormalities were observed at the gastrula
stage but more abnormalities were observed 48 h after
metal exposure. These data demonstrate that changes in
HSC70 levels and phosphorylation state as well as in HSF
and MTF binding activities may be used to rapidly detect
responses to heavy metal exposure. Detection of biochemical
and molecular changes in response to metal
exposure before manifestation of morpho-pathological
effects are important for the prediction of morbidity, and
these markers will be useful for determining the response to exposure as part of a toxicological exposure–response
experiment and for determining responses for an impact
assessment
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