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E Corbin

Publications and source records attributed to E Corbin.

8 recordsLinked to original sources

Coordinate and independent regulation of alpha B-crystallin and hsp27 expression in response to physiological stress.

alpha-Crystallins share structural and functional properties with the stress protein hsp27. These polypeptides are expressed at low constitutive levels in many tissues including brain, and alpha B-crystallin and hsp27 can accumulate in central nervous system glia in a variety of neurological conditions. We report here that heat shock and exposure to transition metals result in an increase in the steady state mRNA level of alpha B-crystallin and hsp27 in primary cultures of rat forebrain astrocytes. Both exposure to tumour necrosis factor-alpha and hypertonic conditions result in alpha B-crystallin mRNA accumulation but no change in the hsp27 mRNA level. Under some of these conditions increased synthesis and accumulation of alpha B-crystallin and hsp27 protein are also evident. We are unable to detect alpha A-crystallin mRNA in resting or stressed astrocytes. A novel phenomenon involving a transitory change in stress protein mRNA mobility in Northern blots during induction is reported, which is stress type and cell type independent. The results demonstrate multiple stress regulation of alpha B-crystallin and hsp27 in cultured astrocytes, suggesting that they can legitimately be regarded as stress proteins in the central nervous system.

Animals↗

Overexpression and abnormal modification of the stress proteins alpha B-crystallin and HSP27 in Alexander disease.

Alexander disease is a leukodystrophy characterized by the presence of numerous Rosenthal fibers, inclusion bodies in astrocytes. A major component of Rosenthal fibers is alpha B-crystallin, some of which is ubiquitinated. In this report, we show that Alexander central nervous system (CNS) tissues contain elevated messenger RNA and protein levels of both alpha B-crystallin and the related small heat shock protein, hsp27, and that Rosenthal fibers contain hsp27. The alpha B-crystallin and hsp27 polypeptide isoform patterns of Alexander disease CNS are also distinct from those of control samples, suggesting that postranslational modifications may be involved in Rosenthal fiber formation. We advance the hypothesis that Rosenthal fibers may be regarded as stress protein inclusions formed in astrocytes as part of a chronic stress response to an as yet unknown stimulus in the CNS of Alexander patients.

Astrocytes↗

Accumulation of alpha B-crystallin in central nervous system glia and neurons in pathologic conditions.

Alpha B-crystallin, a major protein of the vertebrate lens, is found in the central nervous system (CNS) and is a major protein component of Rosenthal fibers (RF), intracytoplasmic inclusions within astrocytes. Its level of expression in the normal CNS is low and appears to be confined to glial cells, both astrocytes and oligodendrocytes. A number of human brains displaying a variety of pathologic changes were examined by immunohistochemistry with an anti-alpha B-crystallin antiserum and increased immunoreactivity was found in astrocytes and oligodendrocytes without the formation of RFs. Furthermore, some neurons in neurodegenerative disorders were also immunolabeled with the anti-alpha B-crystallin antiserum. Thus, the accumulation of alpha B-crystallin appears to be part of the repertoire of reactive processes of CNS glial cells and some neurons in pathologic conditions.

Animals↗

Rosenthal fibers contain ubiquitinated alpha B-crystallin.

The vertebrate lens protein, alpha B-crystallin, is a major component of Rosenthal fibers (RFs) inclusion in astrocytes in Alexander's disease. Antibodies to ubiquitin bind to RFs, but it is not known whether the ubiquitin associated with RFs is bound to a specific protein or proteins, and if so, what the identity of the conjugates is. The authors have analyzed the proteins of RFs from Alexander's disease and have found mono- and polyubiquitinated conjugates of alpha B-crystallin.

Antibodies↗

Isolation of a major protein component of Rosenthal fibers.

Rosenthal fibers (RFs) are inclusions within astrocytes, characteristic of Alexander's disease, but also seen in astrocytic tumors and occasionally in glial scar tissue. They are granular deposits, intimately associated with intermediate filaments. Their composition has been unknown. The authors have isolated a protein of about 19 kd from partially purified RFs from Alexander's disease central nervous system tissue. Antibodies were raised to this protein and shown to react with it on nitrocellulose blots and to bind to RFs in tissue sections. Small amounts of this protein were detected in normal brain and in cultured rat astrocytes. Charge heterogeneity was inferred because several species were separated by isoelectric focusing.

Animals↗