Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells

I. Farkas, L. Baranyi, Z. Liposits, T. Yamamoto, H. Okada

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Human neuroblastoma TGW cells express a C5a anaphylatoxin receptor-like molecule termed neuronal C5a receptor. A C5a-receptor fragment peptide (termed PR226-multiple antigenic peptide) can induce rapid apoptosis in TGW cells via neuronal C5a receptor-associated signal transduction pathways. In order to analyse role of activated complement system in neurodegeneration, TGW cells were exposed to an oligomer form of a C5a fragment (amino acids: 37-53) peptide termed PL37-multiple antigenic peptide. Upon treatment with PL37-multiple antigenic peptide, an increased nuclear c-fos expression was shown within 30 min. DNA fragmentation, a hallmark of apoptosis, was noted within 4 h. Extracellular administration of 100 nM PL37-multiple antigenic peptide evoked inward calcium current pulses. At higher doses (0.5 μM-1 μM), PL37-multiple antigenic peptide evoked higher current pulses, followed by an irreversible, high inward current. To exert its apoptotic effect, PL37- multiple antigenic peptide utilizes a pertussis toxin-sensitive signal transduction pathway associated with the neuronal C5a receptor. Activation of the complement system and therefore release of C5a has already been reported in Alzheimer's disease. In addition, the presence of the Kunitz-type proteinase inhibitors indicates an impaired protease function and a possible abnormal fragmentation of C5a anaphylatoxin. Our data suggest that neurons expressing neuronal C5a receptor are more vulnerable to the apoptosis associated with the neuronal C5a receptor and the possibility that abnormal activation of C5a receptor and C5a anaphylatoxin fragments might be involved in the pathogenesis of Alzheimer's disease.

Original languageEnglish
Pages (from-to)903-911
Number of pages9
JournalNeuroscience
Volume86
Issue number3
DOIs
Publication statusPublished - Jun 8 1998

Fingerprint

Anaphylatoxin C5a Receptor
Complement C5a
Anaphylatoxins
Neuroblastoma
Apoptosis
Peptides
Signal Transduction
Alzheimer Disease
Peptide Hydrolases
Peptide Fragments
Complement Activation
Pertussis Toxin
DNA Fragmentation
Calcium
Neurons
Amino Acids

Keywords

  • Alzheimer's disease
  • Antisense peptide
  • Apoptosis
  • C5a receptor
  • G- proteins
  • Patch clamp

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells. / Farkas, I.; Baranyi, L.; Liposits, Z.; Yamamoto, T.; Okada, H.

In: Neuroscience, Vol. 86, No. 3, 08.06.1998, p. 903-911.

Research output: Contribution to journalArticle

Farkas, I. ; Baranyi, L. ; Liposits, Z. ; Yamamoto, T. ; Okada, H. / Complement C5a anaphylatoxin fragment causes apoptosis in TGW neuroblastoma cells. In: Neuroscience. 1998 ; Vol. 86, No. 3. pp. 903-911.
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