The role of ribosylated-BSA in regulating PC12 cell viability

Tsun Yung Kuo, Chuen Lin Huang, Jung Mou Yang, Wei Jung Huang, Nai Kuei Huang, Yue Wen Chen, Ren Jye Lin, Ying Chen Yang

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Glycation, one of the post-translational modifications, is known to influence protein structure and biological function. Advanced glycation end products (AGEs) have been shown to cause pathologies of diabetes. Glycation levels in patients with Alzheimer's disease (AD) are higher than in normal people. However, whether the glycation of susceptible proteins is a triggering event for cell damage or simply a result remains to be elucidated. In this study, we demonstrated that ribose-conjugated BSA (Rib-BSA) directly induces PC12 cell death in a dose- and time-dependent manner. The IC 50 is 4.6 μM. Unlike glucoseincubated BSA, Rib-BSA rapidly forms cytotoxic AGEs. PC12 is vulnerable to Rib-BSA. However, fructose can induce AGE formation, although no effect on cell survival was observed. This effect of Rib-BSA is reversed by pretreatment of pioglitazone and rosiglitazone, which belongs to thiazolidinediones (TZDs) and are peroxisome proliferator-activated receptor (PPAR-γ) ligands. Moreover, Rib-BSA upregulates inducible nitric oxide synthase (iNOS), cycloxygenase 2 (COX-2) expression, and p-38 phosphorylation and leaves extracellular regulated protein1/2 (ERK1/2) phosphorylation unchanged. The Rib-BSA-induced signaling changes are blocked by rosiglitazone and confirmed by PPAR-γ small-interfering RNA transfection. The reduction of cell survival by Rib-BSA is blocked by the iNOS inhibitor and p38 inhibitor. No effect on cell survival was observed using the COX-2 inhibitor. Consequently, these results show that Rib-BSA directly inducing PC12 cell death is a triggering event and TZDs protect PC12 cell from Rib-BSA damage. Signaling molecules, such as PPAR-γ, P38, and iNOS, are involved in Rib-BSA-mediated cytotoxicity.

Original languageEnglish
Pages (from-to)255-267
Number of pages13
JournalCell Biology and Toxicology
Volume28
Issue number4
DOIs
Publication statusPublished - Aug 2012

Fingerprint

Ribose
PC12 Cells
Cell Survival
Cells
rosiglitazone
Peroxisome Proliferator-Activated Receptors
Nitric Oxide Synthase Type II
Thiazolidinediones
Phosphorylation
pioglitazone
Cell death
Cell Death
Advanced Glycosylation End Products
Pathology
Post Translational Protein Processing
Cytotoxicity
Medical problems
Fructose
Small Interfering RNA
Transfection

Keywords

  • AGE
  • Cytotoxicity
  • Pc12
  • Rib-BSA
  • Rosiglitazone

ASJC Scopus subject areas

  • Cell Biology
  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Kuo, T. Y., Huang, C. L., Yang, J. M., Huang, W. J., Huang, N. K., Chen, Y. W., ... Yang, Y. C. (2012). The role of ribosylated-BSA in regulating PC12 cell viability. Cell Biology and Toxicology, 28(4), 255-267. https://doi.org/10.1007/s10565-012-9220-3

The role of ribosylated-BSA in regulating PC12 cell viability. / Kuo, Tsun Yung; Huang, Chuen Lin; Yang, Jung Mou; Huang, Wei Jung; Huang, Nai Kuei; Chen, Yue Wen; Lin, Ren Jye; Yang, Ying Chen.

In: Cell Biology and Toxicology, Vol. 28, No. 4, 08.2012, p. 255-267.

Research output: Contribution to journalArticle

Kuo, TY, Huang, CL, Yang, JM, Huang, WJ, Huang, NK, Chen, YW, Lin, RJ & Yang, YC 2012, 'The role of ribosylated-BSA in regulating PC12 cell viability', Cell Biology and Toxicology, vol. 28, no. 4, pp. 255-267. https://doi.org/10.1007/s10565-012-9220-3
Kuo TY, Huang CL, Yang JM, Huang WJ, Huang NK, Chen YW et al. The role of ribosylated-BSA in regulating PC12 cell viability. Cell Biology and Toxicology. 2012 Aug;28(4):255-267. https://doi.org/10.1007/s10565-012-9220-3
Kuo, Tsun Yung ; Huang, Chuen Lin ; Yang, Jung Mou ; Huang, Wei Jung ; Huang, Nai Kuei ; Chen, Yue Wen ; Lin, Ren Jye ; Yang, Ying Chen. / The role of ribosylated-BSA in regulating PC12 cell viability. In: Cell Biology and Toxicology. 2012 ; Vol. 28, No. 4. pp. 255-267.
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