A neuronal C5a receptor and an associated apoptotic signal transduction pathway
I Farkas, L Baranyi, M Takahashi… - The Journal of …, 1998 - Wiley Online Library
I Farkas, L Baranyi, M Takahashi, A Fukuda, Z Liposits, T Yamamoto, H Okada
The Journal of physiology, 1998•Wiley Online Library1 We report the first experimental evidence of a neuronal C5a receptor (nC5aR) in human
cells of neuronal origin. Expression of nC5aR mRNA was demonstrated by the reverse
transcriptase‐polymerase chain reaction (RT‐PCR) in TGW human neuroblastoma cells. 2
Expression of a functional C5aR was supported by the finding that C5a evoked a transient
increase in the intracellular calcium level as measured by flow cytometry (FACS). 3 To
analyse the function of the nC5aR, an antisense peptide fragment of the C5aR was used …
cells of neuronal origin. Expression of nC5aR mRNA was demonstrated by the reverse
transcriptase‐polymerase chain reaction (RT‐PCR) in TGW human neuroblastoma cells. 2
Expression of a functional C5aR was supported by the finding that C5a evoked a transient
increase in the intracellular calcium level as measured by flow cytometry (FACS). 3 To
analyse the function of the nC5aR, an antisense peptide fragment of the C5aR was used …
- 1We report the first experimental evidence of a neuronal C5a receptor (nC5aR) in human cells of neuronal origin. Expression of nC5aR mRNA was demonstrated by the reverse transcriptase‐polymerase chain reaction (RT‐PCR) in TGW human neuroblastoma cells.
- 2Expression of a functional C5aR was supported by the finding that C5a evoked a transient increase in the intracellular calcium level as measured by flow cytometry (FACS).
- 3To analyse the function of the nC5aR, an antisense peptide fragment of the C5aR was used. Previous data showed that a C5aR fragment (a peptide termed PR226) has C5aR agonist and antagonist effects in U‐937 cells depending on the concentration of the peptide. We found that a multiple antigenic peptide (MAP) form of the same peptide (termed PR226‐MAP) induced rapid elevation of nuclear c‐fos immunoreactivity and resulted in DNA fragmentation, a characteristic sign of apoptosis, in TGW cells.
- 4Early electrophysiological events characteristic of apoptosis were also detected: intermittent calcium current pulses were recorded within 1–2 min of peptide administration. C5a pretreatment delayed the onset of this calcium influx.
- 5We also demonstrated that the apoptotic pathway is linked to nC5aR via pertussis toxin‐sensitive G‐proteins.
- 6Although the function of C5a and its receptor on neurons is unknown, these results suggest that an abnormal activation of this signal transduction pathway can result in apoptosis and, subsequently, in neurodegeneration.
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