Involvement of T-complex protein-1delta in dopamine triggered apoptosis in chick embryo sympathetic neurons.
The neurotransmitter dopamine (DA) is capable of inducing apoptosis in post-mitotic sympathetic neurons via its oxidative metabolites. The differential display method was applied to cultured sympathetic neurons in an effort to detect genes whose expression is transcriptionally regulated during the early stages of DA-triggered apoptosis. One of the up-regulated genes was identified as the chick homologue to T-complex polypeptide-1delta (TCP-1delta), a member of the molecular chaperone family of proteins. Each chaperone protein is a complex of seven to nine different subunits. A full-length clone of 1.9 kilobases was isolated containing an open reading frame of 536 amino acids with a predicted molecular weight of 57,736. Comparison with the mouse TCP-1delta revealed 78 and 91% homology on the DNA and protein levels, respectively. Northern blot analysis disclosed a steady and significant increase in mRNA levels of TCP-1delta after DA administration, reaching a peak between 4 and 9 h and declining thereafter. Induction of the TCP-1delta protein levels was also observed as a function of DA treatment. Overexpression of TCP-1delta in sympathetic neurons accelerated DA-induced apoptosis; inhibition of TCP-1delta expression in these neurons using antisense technology significantly reduced DA-induced neuronal death. These findings suggest a functional role for TCP-1delta as a positive mediator of DA-induced neuronal apoptosis.
Zilkha-Falb
R
R
Department of Neurobiochemistry, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel.
Barzilai
A
A
Djaldeti
R
R
Ziv
I
I
Melamed
E
E
Shirvan
A
A
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001483:Base Sequence; D002478:Cells, Cultured; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D002642:Chick Embryo; D003001:Cloning, Molecular; D004298:Dopamine / Q000494:pharmacology*; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D008969:Molecular Sequence Data; D020932:Nerve Growth Factor / Q000172:deficiency / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology; D021122:Protein Subunits; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013564:Sympathetic Nervous System / Q000166:cytology / Q000196:embryology*
D016376:Oligonucleotides, Antisense; D021122:Protein Subunits; D012333:RNA, Messenger; D020932:Nerve Growth Factor; D056404:Chaperonin Containing TCP-1; D018833:Chaperonins; D004298:Dopamine