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Dominant expression of a novel splice variant of caspase-8 in human peripheral blood lymphocytes

T Horiuchi1, D Himeji, H Tsukamoto

  • 1Medicine and Biosystemic Science, Kyushu University Graduate School of Medical Sciences, Fukuoka, Japan. horiuchi@intmed1.med.kyushu-u.ac.jp

Biochemical and Biophysical Research Communications
|June 22, 2000
PubMed

Insights

A novel caspase-8 isoform, caspase-8L, generated by alternative splicing, is predominantly expressed in human immune cells. Imbalanced caspase-8L expression was observed in systemic lupus erythematosus patients, suggesting its role in apoptosis regulation.

Area of Science:

  • Molecular Biology
  • Immunology
  • Cell Biology

Background:

  • Caspase-8 is a key enzyme in apoptosis.
  • Alternative splicing generates multiple caspase-8 isoforms.
  • Some isoforms may regulate apoptosis due to domain variations.

Purpose of the Study:

  • To report a novel longer isoform of caspase-8, termed caspase-8L.
  • To investigate the expression of caspase-8L in human immune cells.
  • To explore the role of caspase-8L in systemic lupus erythematosus (SLE).

Main Methods:

  • Alternative splicing analysis to identify caspase-8L.
  • Reverse transcriptase-polymerase chain reaction (RT-PCR) for transcript expression analysis.
  • Comparison of caspase-8L expression in healthy individuals and SLE patients.

Main Results:

  • A novel caspase-8L isoform was identified, resulting from intron 8 splicing with a 136-bp insertion and frame shift.
  • Caspase-8L transcript showed dominant expression over intact caspase-8 in human peripheral blood lymphocytes (PBL) and T cells.
  • Imbalanced caspase-8L transcript expression was detected in patients with systemic lupus erythematosus (SLE).

Conclusions:

  • Caspase-8L is a novel, alternatively spliced isoform of caspase-8.
  • Caspase-8L is predominantly expressed in human PBL and T cells.
  • The imbalanced expression of caspase-8L in SLE suggests its involvement in apoptosis modulation and potential disease relevance.

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