Induction of BIS Protein During Astroglial and Fibrotic Scar Formation After Mitochondrial Toxin-Mediated Neuronal Injury in Rats.

Abstract

B cell leukemia/lymphoma-2 (Bcl-2)-interacting death suppressor (BIS), also identified as Bcl-2-associated athanogene 3 (BAG3), has been reported to be upregulated in reactive astrocytes after brain insults. The present study was designed to further substantiate the involvement of BIS protein in the astroglial reaction in the striatum of rats treated with the mitochondrial toxin, 3-nitropropionic acid. Weak constitutive immunoreactivity for BIS was observed in astrocytes in the control striatum, whereas its expression was upregulated, along with that of nestin, in the lesioned striatum. In the lesion core, where astrocytes are virtually absent, BIS/nestin double-labeled cells were associated with the vasculature and were identified as perivascular adventitial fibroblasts. By contrast, BIS/nestin double-labeled cells in the perilesional area were reactive astrocytes, which were confined to the border zone contributing to the formation of the astroglial scar; this was evident 3 days post-lesion and increased thereafter progressively throughout the 28-day experimental period. At the ultrastructural level, BIS protein was diffusely localized throughout the cytoplasm within the stained cells. Collectively, our results demonstrate the phenotypic and functional heterogeneity of BIS-positive cells in the lesioned striatum, suggesting the involvement of BIS in the formation of astroglial scar and its potential role in the development of fibrotic scar after brain insults.

• Authors: Tae-Ryong Riew, Soojin Kim, Xuyan Jin, Hong Lim Kim, Kyunghyun Yoo, Sung Bin Seo, Jeong-Hwa Lee, Mun-Yong Lee
• Journal: Molecular neurobiology (Mol Neurobiol) Vol. 57 Issue 9 Pg. 3846-3859 (Sep 2020) ISSN: 1559-1182 [Electronic] United States
• PMID: 32607834 (Publication Type: Journal Article)

Chemical References

• Adaptor Proteins, Signal Transducing
• Apoptosis Regulatory Proteins
• BAG3 protein, rat
• Glial Fibrillary Acidic Protein
• Nestin
• Nitro Compounds
• Propionates
• Toxins, Biological
• 3-nitropropionic acid

Topics

• Adaptor Proteins, Signal Transducing (metabolism)
• Animals
• Apoptosis Regulatory Proteins (metabolism)
• Astrocytes (pathology)
• Brain (drug effects, metabolism)
• Cicatrix (pathology)
• Corpus Striatum (metabolism, pathology, ultrastructure)
• Fibroblasts (metabolism)
• Fibrosis
• Glial Fibrillary Acidic Protein (metabolism)
• Male
• Mitochondria (drug effects, pathology, ultrastructure)
• Nestin (metabolism)
• Neurons (pathology, ultrastructure)
• Nitro Compounds
• Phenotype
• Propionates
• Rats, Sprague-Dawley
• Time Factors
• Toxins, Biological (toxicity)