Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced cell proliferation in rat spleen

Jianling Wang, Gangduo Wang, Huaxian Ma, M Khan

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Aniline exposure is associated with toxicity to the spleen leading to splenomegaly, hyperplasia, fibrosis and a variety of sarcomas of the spleen on chronic exposure. In earlier studies, we have shown that aniline exposure leads to iron overload, oxidative stress and activation of redox-sensitive transcription factors, which could regulate various genes leading to a tumorigenic response in the spleen. However, molecular mechanisms leading to aniline-induced cellular proliferation in the spleen remain largely unknown. This study was, therefore, undertaken on the regulation of G1 phase cell cycle proteins (cyclins), expression of cyclin-dependent kinases (CDKs), phosphorylation of retinoblastoma protein (pRB) and cell proliferation in the spleen, in an experimental condition preceding a tumorigenic response. Male SD rats were treated with aniline (0.5. mmol/kg/day via drinking water) for 30. days (controls received drinking water only), and splenocyte proliferation, protein expression of G1 phase cyclins, CDKs and pRB were measured. Aniline treatment resulted in significant increases in splenocyte proliferation, based on cell counts, cell proliferation markers including proliferating cell nuclear antigen (PCNA), nuclear Ki67 protein (Ki67) and minichromosome maintenance (MCM), MTT assay and flow cytometric analysis. Western blot analysis of splenocyte proteins from aniline-treated rats showed significantly increased expression of cyclins D1, D2, D3 and E, as compared to the controls. Similarly, real-time PCR analysis showed significantly increased mRNA expression for cyclins D1, D2, D3 and E in the spleens of aniline-treated rats. The overexpression of these cyclins was associated with increases in the expression of CDK4, CDK6, CDK2 as well as phosphorylation of pRB protein. Our data suggest that increased expression of cyclins, CDKs and phosphorylation of pRB protein could be critical in cell proliferation, and may contribute to aniline-induced tumorigenic response in the spleen.

Original languageEnglish (US)
Pages (from-to)213-220
Number of pages8
JournalToxicology and Applied Pharmacology
Volume250
Issue number2
DOIs
StatePublished - Jan 15 2011

Fingerprint

Cell proliferation
Protein Kinases
Phosphorylation
Rats
Phosphotransferases
Spleen
Cell Proliferation
Retinoblastoma Protein
Proteins
Cyclin-Dependent Kinases
G1 Phase
Drinking Water
Ki-67 Antigen
Cell Cycle Proteins
Iron Overload
Oxidative stress
aniline
Splenomegaly
Proliferating Cell Nuclear Antigen
Nuclear Proteins

Keywords

  • Aniline
  • CDKs
  • Cell proliferation
  • Cyclins
  • PRB
  • Splenic toxicity

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Enhanced expression of cyclins and cyclin-dependent kinases in aniline-induced cell proliferation in rat spleen. / Wang, Jianling; Wang, Gangduo; Ma, Huaxian; Khan, M.

In: Toxicology and Applied Pharmacology, Vol. 250, No. 2, 15.01.2011, p. 213-220.

Research output: Contribution to journalArticle

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