CG&D
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhu, Y.
Right arrow Articles by Zhang, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhu, Y.
Right arrow Articles by Zhang, L.
Cell Growth & Differentiation Vol. 13, 431-439, September 2002
© 2002 American Association for Cancer Research

Heme Deficiency Interferes with the Ras-Mitogen-activated Protein Kinase Signaling Pathway and Expression of a Subset of Neuronal Genes1

Yonghua Zhu2, Thomas Hon2, Weizhen Ye and Li Zhang3

Department of Biochemistry, New York University School of Medicine, New York, New York 10016

Defective heme synthesis in mammals has been suspected of causing neuropathy associated with porphyrias and lead poisoning. To determine the molecular action of heme in neuronal cells, we examined the effect of the inhibition of heme synthesis on nerve growth factor (NGF) signaling in PC12 cells. We found that the inhibition of heme synthesis by succinyl acetone interferes with NGF-induced neurite outgrowth in PC12 cells. Furthermore, we show that heme deficiency obliterates the activation of the signaling intermediates of the Ras-mitogen-activated protein kinase signaling pathway and its downstream target, the transcription activator cyclic AMP response element-binding protein. Strikingly, microarray expression analysis shows that the inhibition of heme synthesis selectively diminishes the induction of expression of a subset of neuron-specific genes by NGF, such as Ras and neurofilament proteins, whereas NGF induces the expression of several major classes of neuronal genes that encode regulatory and structural proteins at three days after induction. Our data provide insights into how heme deficiency interferes with NGF signaling and abrogates programs of neuronal gene expression, thus ultimately causing defective neuronal functions.




This article has been cited by other articles:


Home page
Infect. Immun.Home page
D. C. Miguel, A. R. Flannery, B. Mittra, and N. W. Andrews
Heme Uptake Mediated by LHR1 Is Essential for Leishmania amazonensis Virulence
Infect. Immun., October 1, 2013; 81(10): 3620 - 3626.
[Abstract] [Full Text] [PDF]


Home page
Poultry ScienceHome page
K. Sato, K. Matsushita, K. Takahashi, M. Aoki, J. Fuziwara, S. Miyanari, and T. Kamada
Dietary supplementation with 5-aminolevulinic acid modulates growth performance and inflammatory responses in broiler chickens
Poultry Science, July 1, 2012; 91(7): 1582 - 1589.
[Abstract] [Full Text] [PDF]


Home page
J Biol ChemHome page
C. Chen, T. K. Samuel, M. Krause, H. A. Dailey, and I. Hamza
Heme Utilization in the Caenorhabditis elegans Hypodermal Cells Is Facilitated by Heme-responsive Gene-2
J. Biol. Chem., March 16, 2012; 287(12): 9601 - 9612.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
T. Chernova, J. R. Steinert, P. Richards, R. Mistry, R. A. J. Challiss, R. Jukes-Jones, K. Cain, A. G. Smith, and I. D. Forsythe
Early Failure of N-Methyl-D-aspartate Receptors and Deficient Spine Formation Induced by Reduction of Regulatory Heme in Neurons
Mol. Pharmacol., May 1, 2011; 79(5): 844 - 854.
[Abstract] [Full Text] [PDF]


Home page
ScienceHome page
L. Yin, N. Wu, J. C. Curtin, M. Qatanani, N. R. Szwergold, R. A. Reid, G. M. Waitt, D. J. Parks, K. H. Pearce, G. B. Wisely, et al.
Rev-erb{alpha}, a Heme Sensor That Coordinates Metabolic and Circadian Pathways
Science, December 14, 2007; 318(5857): 1786 - 1789.
[Abstract] [Full Text] [PDF]


Home page
J. Neurosci.Home page
T. Chernova, J. R. Steinert, C. J. Guerin, P. Nicotera, I. D. Forsythe, and A. G. Smith
Neurite Degeneration Induced by Heme Deficiency Mediated via Inhibition of NMDA Receptor-Dependent Extracellular Signal-Regulated Kinase 1/2 Activation
J. Neurosci., August 8, 2007; 27(32): 8475 - 8485.
[Abstract] [Full Text] [PDF]


Home page
Mol. Biol. CellHome page
R. Sannerud, M. Marie, C. Nizak, H. A. Dale, K. Pernet-Gallay, F. Perez, B. Goud, and J. Saraste
Rab1 Defines a Novel Pathway Connecting the Pre-Golgi Intermediate Compartment with the Cell Periphery
Mol. Biol. Cell, April 1, 2006; 17(4): 1514 - 1526.
[Abstract] [Full Text] [PDF]


Home page
J BiochemHome page
N. Shinjyo and K. Kita
Up-Regulation of Heme Biosynthesis during Differentiation of Neuro2a Cells.
J. Biochem., March 1, 2006; 139(3): 373 - 381.
[Abstract] [Full Text] [PDF]


Home page
Mol. Pharmacol.Home page
T. Chernova, P. Nicotera, and A. G. Smith
Heme Deficiency Is Associated with Senescence and Causes Suppression of N-Methyl-D-aspartate Receptor Subunits Expression in Primary Cortical Neurons
Mol. Pharmacol., March 1, 2006; 69(3): 697 - 705.
[Abstract] [Full Text] [PDF]


Home page
J. Pharmacol. Exp. Ther.Home page
X.-M. Han, G. Lee, C. Hefner, J. J. Maher, and M. A. Correia
Heme-Reversible Impairment of CYP2B1/2 Induction in Heme-Depleted Rat Hepatocytes in Primary Culture: Translational Control by a Hepatic {alpha}-Subunit of the Eukaryotic Initiation Factor Kinase?
J. Pharmacol. Exp. Ther., July 1, 2005; 314(1): 128 - 138.
[Abstract] [Full Text] [PDF]


Home page
Mol. Cell. Biol.Home page
H. C. Lee, T. Hon, C. Lan, and L. Zhang
Structural Environment Dictates the Biological Significance of Heme-Responsive Motifs and the Role of Hsp90 in the Activation of the Heme Activator Protein Hap1
Mol. Cell. Biol., August 15, 2003; 23(16): 5857 - 5866.
[Abstract] [Full Text] [PDF]




HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Cancer Research Clinical Cancer Research
Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cell Growth & Differentiation
Copyright © 2002 by the American Association of Cancer Research.