Neuroleukin inhibition sensitises neuronal cells to caspase-dependent apoptosis.
Neuroleukin (NLK) is a multifunctional protein, involved in neuronal growth, glucose metabolism, cell motility, and differentiation. Expressed in the brain, it supports the growth of embryonic spinal, skeletal motor, and sensory neurons. We have previously demonstrated that NLK is up-regulated in the brain during Huntington's disease (HD), a neurodegenerative disorder caused by the expansion of CAG trinucleotide repeats. In order to study the biological role of NLK, we have generated an inducible rat pheochromocytoma PC12 cell line in which the expression of NLK is selectively down-regulated by antisense strategy. We show here that the block of NLK commits PC12 cells to caspase-dependent apoptosis. This priming effect elicited by NLK inhibition is independent from the differentiation state of the neuronal cells. These results suggest a general protective role of NLK in the control of cell death in neuronal cells.
Romagnoli
Alessandra
A
Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Rome, Italy.
Oliverio
Serafina
S
Evangelisti
Cristina
C
Iannicola
Carlo
C
Ippolito
Giuseppe
G
Piacentini
Mauro
M
D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism*; D016923:Cell Death; D018076:DNA, Complementary / Q000378:metabolism; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D005434:Flow Cytometry; D005822:Genetic Vectors; D005956:Glucose-6-Phosphate Isomerase / Q000037:antagonists & inhibitors* / Q000502:physiology*; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009474:Neurons / Q000378:metabolism*; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D016716:PC12 Cells; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection
D000590:Amino Acid Chloromethyl Ketones; D018076:DNA, Complementary; D008164:Luminescent Proteins; D016376:Oligonucleotides, Antisense; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D049452:Green Fluorescent Proteins; D020169:Caspases; D005956:Glucose-6-Phosphate Isomerase