An examination of heme action in gene expression: heme and heme deficiency affect the expression of diverse genes in erythroid k562 and neuronal PC12 cells.
The aim of this study was to identify key genes whose expression is altered by heme and heme deficiency in the human erythroleukemia K562 cells and in the NGF-induced rat pheochromocytoma neuronal PC12 cells, respectively. By quantitative RT-PCR, Northern blotting, and Western blotting analyses, we found that the expression of the CDK inhibitors p18 and p21 was upregulated at the early and late stages of heme-induced erythroid differentiation of K562 cells, respectively, while the expression of cyclin D1 was downregulated. Data from succinyl acetone and desferrioxamine treatments suggest that these effects of heme in K562 cells were specific. Further, by microarray expression analysis, we found that inhibition of heme synthesis by succinyl acetone in NGF-induced PC12 cells drastically altered the expression of several groups of important neuronal genes, including the structural genes encoding neurofilament proteins and synaptic vesicle proteins, regulatory genes encoding signaling components beta-arrestin and p38 MAPK, and stress-response genes encoding hsp70. These results show that heme and heme deficiency affect the expression of diverse genes in a cell-type specific manner in mammalian cells, and that heme, although needed at different levels, is critical for both erythropoiesis and neurogenesis. These studies provide insights into how heme may act to control diverse regulatory processes in mammals.
Zhu
Yonghua
Y
Department of Biochemistry, NYU School of Medicine, New York, NY 10016, USA.
Lee
Hee Chul
HC
Zhang
Li
L
D000199:Actins / Q000235:genetics; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics; D019938:Cyclin D1 / Q000235:genetics; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000235:genetics; D003676:Deferoxamine / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004920:Erythropoiesis / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D006418:Heme / Q000172:deficiency / Q000235:genetics*; D006537:Heptanoates / Q000494:pharmacology; D006801:Humans; D007502:Iron Chelating Agents / Q000494:pharmacology; D020014:K562 Cells; D009474:Neurons / Q000166:cytology / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D016716:PC12 Cells; D051381:Rats; D025521:Tumor Suppressor Proteins / Q000235:genetics
D000199:Actins; C493956:CDKN1A protein, human; C493971:CDKN2C protein, human; C493958:Cdkn1a protein, rat; C493962:Cdkn1b protein, rat; C493973:Cdkn2c protein, rat; D018797:Cell Cycle Proteins; D050763:Cyclin-Dependent Kinase Inhibitor p18; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004791:Enzyme Inhibitors; D006537:Heptanoates; D007502:Iron Chelating Agents; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D006418:Heme; C020804:succinylacetone; D003676:Deferoxamine