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Implication of mitochondrial involvement in apoptotic activity of fragile histidine triad gene: application of synchronous luminescence spectroscopy.

Publication ,  Journal Article
Askari, MDF; Vo-Dinh, T
Published in: Biopolymers
March 2004

The fragile histidine triad (FHIT) tumor suppressor gene incorporates the common human chromosomal fragile site at 3p14.2. The structure and expression of the FHIT gene are frequently altered in many cancers. The tumor suppressor activity of the FHIT gene has been previously demonstrated as potentially involving apoptotic induction. Here, mitochondria are implicated as being involved in the apoptotic activity of the FHIT gene. A number of morphological and biochemical events, including the disruption of the inner mitochondrial transmembrane potential (Delta Psi(m)) and the release of apoptogenic cytochrome c protein into the cytoplasm, are characteristic features of the apoptotic program. The proapoptotic activity of the FHIT gene is studied by investigating the loss of Delta Psi(m) in mitochondria and translocation of cytochrome c. Synchronous luminescence (SL) spectroscopy is applied to measure mitochondrial incorporation of rhodamine 123 for direct analysis of alterations in the mitochondrial Delta Psi(m). The SL methodology is based on synchronous excitation in which the excitation and emission wavelengths are scanned simultaneously while a constant wavelength interval is maintained between the excitation and emission monochromators. An enhanced collapse of Delta Psi(m) in apoptotically induced FHIT expressing cells compared to FHIT negative cells is observed. The loss of Delta Psi(m) is greatly restricted in the presence of the apoptotic inhibitor, cyclosporin A. Cytoplasmic translocation of cytochrome c in the FHIT expressing cells as an early event in apoptosis is also demonstrated. It is concluded that Fhit protein expression maintained apoptotic function by altering the Delta Psi(m) and by enhancing cytochrome c efflux from the mitochondria.

Duke Scholars

Published In

Biopolymers

DOI

EISSN

1097-0282

ISSN

0006-3525

Publication Date

March 2004

Volume

73

Issue

4

Start / End Page

510 / 523

Related Subject Headings

  • Time Factors
  • Stomach Neoplasms
  • Spectrum Analysis
  • Rhodamine 123
  • Neoplasm Proteins
  • Mitochondria
  • Membrane Potentials
  • Luminescent Measurements
  • Humans
  • Genes, Tumor Suppressor
 

Citation

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ICMJE
MLA
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Journal cover image

Published In

Biopolymers

DOI

EISSN

1097-0282

ISSN

0006-3525

Publication Date

March 2004

Volume

73

Issue

4

Start / End Page

510 / 523

Related Subject Headings

  • Time Factors
  • Stomach Neoplasms
  • Spectrum Analysis
  • Rhodamine 123
  • Neoplasm Proteins
  • Mitochondria
  • Membrane Potentials
  • Luminescent Measurements
  • Humans
  • Genes, Tumor Suppressor