Bcl-2 expression in synovial fibroblasts is essential for maintaining mitochondrial homeostasis and cell viability - PubMed (original) (raw)

Comparative Study

. 2000 May 15;164(10):5227-35.

doi: 10.4049/jimmunol.164.10.5227.

Affiliations

• PMID: 10799883
• DOI: 10.4049/jimmunol.164.10.5227

Comparative Study

Bcl-2 expression in synovial fibroblasts is essential for maintaining mitochondrial homeostasis and cell viability

H Perlman et al. J Immunol. 2000.

Abstract

The regulation of proliferation and cell death is vital for homeostasis, but the mechanism that coordinately balances these events in rheumatoid arthritis (RA) remains largely unknown. In RA, the synovial lining thickens in part through increased proliferation and/or decreased synovial fibroblast cell death. Here we demonstrate that the anti-apoptotic protein, Bcl-2, is highly expressed in RA compared with osteoarthritis synovial tissues, particularly in the CD68-negative, fibroblast-like synoviocyte population. To determine the importance of endogenous Bcl-2, an adenoviral vector expressing a hammerhead ribozyme to Bcl-2 (Ad-Rbz-Bcl-2) mRNA was employed. Ad-Rbz-Bcl-2 infection resulted in reduced Bcl-2 expression and cell viability in synovial fibroblasts isolated from RA and osteoarthritis synovial tissues. In addition, Ad-Rbz-Bcl-2-induced mitochondrial permeability transition, cytochrome c release, activation of caspases 9 and 3, and DNA fragmentation. The general caspase inhibitor zVAD.fmk blocked caspase activation, poly(ADP-ribose) polymerase cleavage, and DNA fragmentation, but not loss of transmembrane potential or viability, indicating that cell death was independent of caspase activation. Ectopically expressed Bcl-xL inhibited Ad-Rbz-Bcl-2-induced mitochondrial permeability transition and apoptosis in Ad-Rbz-Bcl-2-transduced cells. Thus, forced down-regulation of Bcl-2 does not induce a compensatory mechanism to prevent loss of mitochondrial integrity and cell death in human fibroblasts.

PubMed Disclaimer

Similar articles

• Down-regulation of myeloid cell leukemia 1 by epigallocatechin-3-gallate sensitizes rheumatoid arthritis synovial fibroblasts to tumor necrosis factor alpha-induced apoptosis.
  Ahmed S, Silverman MD, Marotte H, Kwan K, Matuszczak N, Koch AE. Ahmed S, et al. Arthritis Rheum. 2009 May;60(5):1282-93. doi: 10.1002/art.24488. Arthritis Rheum. 2009. PMID: 19404960 Free PMC article.
• Death signals from the B cell antigen receptor target mitochondria, activating necrotic and apoptotic death cascades in a murine B cell line, WEHI-231.
  Doi T, Motoyama N, Tokunaga A, Watanabe T. Doi T, et al. Int Immunol. 1999 Jun;11(6):933-41. doi: 10.1093/intimm/11.6.933. Int Immunol. 1999. PMID: 10360967
• PUMA regulation and proapoptotic effects in fibroblast-like synoviocytes.
  Cha HS, Rosengren S, Boyle DL, Firestein GS. Cha HS, et al. Arthritis Rheum. 2006 Feb;54(2):587-92. doi: 10.1002/art.21631. Arthritis Rheum. 2006. PMID: 16447235
• Regulation of apoptosis and cell cycle activity in rheumatoid arthritis.
  Perlman H, Pagliari LJ, Volin MV. Perlman H, et al. Curr Mol Med. 2001 Nov;1(5):597-608. doi: 10.2174/1566524013363429. Curr Mol Med. 2001. PMID: 11899234 Review.
• Mitochondria and programmed cell death: back to the future.
  Petit PX, Susin SA, Zamzami N, Mignotte B, Kroemer G. Petit PX, et al. FEBS Lett. 1996 Oct 28;396(1):7-13. doi: 10.1016/0014-5793(96)00988-x. FEBS Lett. 1996. PMID: 8906857 Review.

Cited by

• Mechanistic target of rapamycin (mTOR): a potential new therapeutic target for rheumatoid arthritis.
  Zhang F, Cheng T, Zhang SX. Zhang F, et al. Arthritis Res Ther. 2023 Oct 2;25(1):187. doi: 10.1186/s13075-023-03181-w. Arthritis Res Ther. 2023. PMID: 37784141 Free PMC article. Review.
• Leucocyte Abnormalities in Synovial Fluid of Degenerative and Inflammatory Arthropathies.
  Baggio C, Luisetto R, Boscaro C, Scanu A, Ramonda R, Albiero M, Sfriso P, Oliviero F. Baggio C, et al. Int J Mol Sci. 2023 Mar 13;24(6):5450. doi: 10.3390/ijms24065450. Int J Mol Sci. 2023. PMID: 36982526 Free PMC article.
• Mitochondrial Dysfunction and Oxidative Stress in Rheumatoid Arthritis.
  López-Armada MJ, Fernández-Rodríguez JA, Blanco FJ. López-Armada MJ, et al. Antioxidants (Basel). 2022 Jun 12;11(6):1151. doi: 10.3390/antiox11061151. Antioxidants (Basel). 2022. PMID: 35740048 Free PMC article. Review.
• Apoptosis, Autophagy, NETosis, Necroptosis, and Pyroptosis Mediated Programmed Cell Death as Targets for Innovative Therapy in Rheumatoid Arthritis.
  Zhao J, Jiang P, Guo S, Schrodi SJ, He D. Zhao J, et al. Front Immunol. 2021 Dec 24;12:809806. doi: 10.3389/fimmu.2021.809806. eCollection 2021. Front Immunol. 2021. PMID: 35003139 Free PMC article. Review.
• Human Cytomegalovirus Host Interactions: EGFR and Host Cell Signaling Is a Point of Convergence Between Viral Infection and Functional Changes in Infected Cells.
  Lee BJ, Min CK, Hancock M, Streblow DN, Caposio P, Goodrum FD, Yurochko AD. Lee BJ, et al. Front Microbiol. 2021 May 7;12:660901. doi: 10.3389/fmicb.2021.660901. eCollection 2021. Front Microbiol. 2021. PMID: 34025614 Free PMC article. Review.

Publication types

MeSH terms

Substances

LinkOut - more resources

• Full Text Sources

  • Silverchair Information Systems

• Other Literature Sources

  • The Lens - Patent Citations Database

• Research Materials

  • NCI CPTC Antibody Characterization Program

• Miscellaneous

  • SciCrunch