Neuregulin-1 isoform induces mitogenesis, KCa and Ca2+ currents in PC12 cells. A comparison with sciatic nerve conditioned medium.
Neuregulin-1 (NRG-1) is an active component found in sciatic nerve conditioned medium (CM). NRG-1 is a growth and differentiation factor shown to have an effect on neuritogenesis and survival of neural cells. PC12 cells chronically treated with NRG-1 (beta1 isoform) show an increase in proliferation under low-serum condition (2.5% fetal bovine serum and 1.25% horse serum) and serum deprivation, without visible morphological changes. NRG-1 and CM treatments of PC12 cells induced an increase of voltage-activated Ca2+ currents and large-conductance calcium-activated K+ currents (KCa). AG825, a specific inhibitor for erbB2 receptor, abolishes KCa current, though Ca2+ currents were not inhibited. These results showed that NRG-1 is capable of inducing functional changes but is not sufficient on its own to have an effect on cell morphology.
Castillo
Cecilia
C
Centro de Biociencias y Medicina Molecular, Instituto de Estudios Avanzados-IDEA, Apartado 17606, Caracas, Venezuela. ccastill@reacciun.ve
Malavé
Caridad
C
Martínez
Juan Carlos
JC
Núñez
Jorge
J
Hernández
Deyanell
D
Pasquali
Fabiola
F
Villegas
Gloria M
GM
Villegas
Raimundo
R
D000704:Analysis of Variance; D000818:Animals; D052160:Benzothiazoles / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D018999:Charybdotoxin / Q000494:pharmacology; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016895:Culture Media, Serum-Free / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007462:Iodobenzenes / Q000494:pharmacology; D020890:Neuregulin-1 / Q000494:pharmacology*; D009498:Neurotoxins / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects*; D018408:Patch-Clamp Techniques / Q000379:methods; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D020033:Protein Isoforms / Q000494:pharmacology; D051381:Rats; D018719:Erb-b2 Receptor Tyrosine Kinases; D012584:Sciatic Nerve / Q000737:chemistry; D020032:Tyrphostins / Q000494:pharmacology
D052160:Benzothiazoles; D015220:Calcium Channels; D018999:Charybdotoxin; D017077:Culture Media, Conditioned; D016895:Culture Media, Serum-Free; D006023:Glycoproteins; D007462:Iodobenzenes; D020890:Neuregulin-1; D009498:Neurotoxins; D024681:Potassium Channels, Calcium-Activated; D020033:Protein Isoforms; D018719:Erb-b2 Receptor Tyrosine Kinases; D020032:Tyrphostins; C098214:tyrphostin AG825; C476101:o-iodoxybenzoic acid; C483804:Erbb2 protein, rat