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Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy zone protein and alpha2-macroglobulin.
J Neurosci Res. 2002 Oct 01; 70(1):57-64.JN

Abstract

Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma protein closely related to human alpha(2)-macroglobulin (alpha(2)M). It has been demonstrated that monoamine-activated forms of human and rat alpha(2)M and rat alpha(1)M can bind to TrkA and, respectively, inhibit and stimulate NGF-promoted neurite outgrowth, Trk phosphorylation, and intracellular signal transduction in PC12 cells. However, the effect of PZP on neurons is unknown, and the molecular mechanism of neuroinhibition by monoamine-activated alpha(2)M is still unclear. In this report, we show that methylamine-activated PZP (MA-PZP), like MA-alpha(2)M, inhibits in a dose-dependent way the NGF-promoted neurite extension and TrkA phosphorylation in PC12 cells. On the other hand, normal PZP (N-PZP) had little or no effect. In addition, the inhibitory effect of activated alpha-macroglobulins (alphaMs) was reversible upon its removal from the cell culture. In addition, PZP, as well as alpha(2)M, is neuroinhibitory without being directly cytotoxic. It is known that the activated alphaMs bind to the multiligand receptor termed low-density lipoprotein receptor-related protein (LRP) and that the receptor-associated protein (RAP) specifically blocks uptake of all known LRP ligands. To investigate the potential role of LRP in neuromodulation by activated PZP/alpha(2)M, the effect of RAP on the neuroinhibitory activities of these alphaMs was also studied. Data presented here show that RAP blocked the neurite- and Trk-inhibitory activities of both MA-PZP and MA-alpha(2)M, whereas RAP itself had no neuromodulatory effect. Hence, we conclude that these data suggest that the LRP receptor and its alphaM ligands may play a role in regulating Trk receptors.

Authors+Show Affiliations

Departamento de Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina. gustavo@bioclin.fcq.unc.edu.arNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

12237864

Citation

Chiabrando, Gustavo A., et al. "Low-density Lipoprotein Receptor-related Protein Mediates in PC12 Cell Cultures the Inhibition of Nerve Growth Factor-promoted Neurite Outgrowth By Pregnancy Zone Protein and Alpha2-macroglobulin." Journal of Neuroscience Research, vol. 70, no. 1, 2002, pp. 57-64.
Chiabrando GA, Sánchez MC, Skornicka EL, et al. Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy zone protein and alpha2-macroglobulin. J Neurosci Res. 2002;70(1):57-64.
Chiabrando, G. A., Sánchez, M. C., Skornicka, E. L., & Koo, P. H. (2002). Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy zone protein and alpha2-macroglobulin. Journal of Neuroscience Research, 70(1), 57-64.
Chiabrando GA, et al. Low-density Lipoprotein Receptor-related Protein Mediates in PC12 Cell Cultures the Inhibition of Nerve Growth Factor-promoted Neurite Outgrowth By Pregnancy Zone Protein and Alpha2-macroglobulin. J Neurosci Res. 2002 Oct 1;70(1):57-64. PubMed PMID: 12237864.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Low-density lipoprotein receptor-related protein mediates in PC12 cell cultures the inhibition of nerve growth factor-promoted neurite outgrowth by pregnancy zone protein and alpha2-macroglobulin. AU - Chiabrando,Gustavo A, AU - Sánchez,María C, AU - Skornicka,Erin L, AU - Koo,Peter H, PY - 2002/9/19/pubmed PY - 2002/11/26/medline PY - 2002/9/19/entrez SP - 57 EP - 64 JF - Journal of neuroscience research JO - J Neurosci Res VL - 70 IS - 1 N2 - Human pregnancy zone protein (PZP) is a major pregnancy-associated plasma protein closely related to human alpha(2)-macroglobulin (alpha(2)M). It has been demonstrated that monoamine-activated forms of human and rat alpha(2)M and rat alpha(1)M can bind to TrkA and, respectively, inhibit and stimulate NGF-promoted neurite outgrowth, Trk phosphorylation, and intracellular signal transduction in PC12 cells. However, the effect of PZP on neurons is unknown, and the molecular mechanism of neuroinhibition by monoamine-activated alpha(2)M is still unclear. In this report, we show that methylamine-activated PZP (MA-PZP), like MA-alpha(2)M, inhibits in a dose-dependent way the NGF-promoted neurite extension and TrkA phosphorylation in PC12 cells. On the other hand, normal PZP (N-PZP) had little or no effect. In addition, the inhibitory effect of activated alpha-macroglobulins (alphaMs) was reversible upon its removal from the cell culture. In addition, PZP, as well as alpha(2)M, is neuroinhibitory without being directly cytotoxic. It is known that the activated alphaMs bind to the multiligand receptor termed low-density lipoprotein receptor-related protein (LRP) and that the receptor-associated protein (RAP) specifically blocks uptake of all known LRP ligands. To investigate the potential role of LRP in neuromodulation by activated PZP/alpha(2)M, the effect of RAP on the neuroinhibitory activities of these alphaMs was also studied. Data presented here show that RAP blocked the neurite- and Trk-inhibitory activities of both MA-PZP and MA-alpha(2)M, whereas RAP itself had no neuromodulatory effect. Hence, we conclude that these data suggest that the LRP receptor and its alphaM ligands may play a role in regulating Trk receptors. SN - 0360-4012 UR - https://www.unboundmedicine.com/medline/citation/12237864/Low_density_lipoprotein_receptor_related_protein_mediates_in_PC12_cell_cultures_the_inhibition_of_nerve_growth_factor_promoted_neurite_outgrowth_by_pregnancy_zone_protein_and_alpha2_macroglobulin_ L2 - https://doi.org/10.1002/jnr.10369 DB - PRIME DP - Unbound Medicine ER -