Progressive supranuclear palsy (PSP) and corticobasal degeneration (CBD) are neurodegenerative diseases that are characterized by intracytoplasmic aggregates of hyperphosphorylated tau with four microtubule‐binding repeats. Although PSP and CBD have distinctive pathological features, no biochemical difference in aggregated tau has been identified. In this study, we examined the brains of eight patients with PSP, six patients with CBD, and one atypical case with pathological features of both CBD and PSP. On immunoblots of sarkosyl‐insoluble brain extracts, a 33kDa band predominated in the low molecular weight tau fragments in PSP, whereas two closely related bands of approximately 37kDa predominated in CBD. Immunoblots of the atypical case showed both the 33kDa band and the 37kDa doublet. Protein sequencing and immunochemical analyses showed that the 33kDa band and the 37kDa doublet consisted of the carboxyl half of tau with different amino termini. These results suggest that, despite the identical composition of tau isoforms, different proteolytic processing of abnormal tau takes place in these two diseases. Such a biochemical divergence may be related to the neuropathological features of these diseases.
To investigate the mechanism of persistent proliferation of rheumatoid arthritis (RA) synoviocytes in situ, we examined the activity of telomerase enzyme and the expression of telomerase related factors in cultured synoviocytes. Cultured synoviocytes obtained from patients with rheumatoid arthritis (n = 29), osteoarthritis (OA, n = 18), and traumatic joint disease (TJD, n = 4) were examined. Telomerase activity was detected by TRAP (telomeric repeat amplification protocol) assay, and 12 out of 29 samples of synoviocytes (41%) from RA patients showed a positive telomerase activity, whereas none of the samples from OA and TJD patients showed this activity. Results were confirmed by PCR-ELISA. The telomerase activity was enhanced by basic fibroblast growth factor (bFGF). The mRNA expression of telomerase related factors, such as hTERC, TRF2, and TEP-1, showed no difference between RA and OA synoviocytes. Our results suggest that telomerase is activated in rheumatoid synoviocytes, and that bFGF upregulates the activity of this enzyme in RA synoviocytes.
To investigate the mechanism of synovial hyperplasia by human T-lymphotropic virus type I (HTLV-I) infection, the enzymatic activity of telomerase and expression of telomerase-related factors in HTLV-I infected synoviocytes were examined. Cultured synoviocytes obtained from four patients with osteoarthritis (OA) and four with traumatic joint disease (TJD) were infected by HTLV-I. Telomerase activity was detected by telomeric repeat amplification protocol (TRAP) assay. Expression of telomerase-related mRNAs such as telomerase reverse transcriptase (hTERT), telomerase RNA component (hTERC), and telomeric repeat binding factor 2 (TRF2) were also examined. Telomerase activity was detected in all HTLV-I-infected synoviocytes but not in uninfected synoviocytes. A remarkable induction of hTERT mRNA was observed in four of eight HTLV-I-infected synoviocytes, whereas expressions of hTERC, TRF2, and TEP-1 mRNAs were not changed. Our results clearly demonstrate that HTLV-I upregulates telomerase activity in synoviocytes probably via upregulation of hTERT activity. These findings suggest that telomerase activation in synoviocytes has an important role in upregulated proliferative activity of HAAP synoviocytes.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.