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

Zhu, Yonghua; Lee, Hee Chul; Zhang, Li
April 2002
DNA & Cell Biology;Apr2002, Vol. 21 Issue 4, p333
Academic Journal
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 �-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.


Related Articles

  • Aucubin modulates Bcl-2 family proteins expression and inhibits caspases cascade in HO-induced PC12 cells. Hong Yu Xue; Dong Yan Niu; Gui Zhen Gao; Qiu Ye Lin; Li Ji Jin; Yong Ping Xu // Molecular Biology Reports;Jun2011, Vol. 38 Issue 5, p3561 

    In this study, the effect of aucubin on HO-induced apoptosis was studied by using a rat pheochromocytoma (PC12) cell line. We have analyzed the apoptosis of HO-induced PC12 cells, HO-induced apoptosis appeared to correlate with lower Bcl-2 expression, higher Bax expression and sequential...

  • Induction of Heme-Binding Protein 23/Peroxiredoxin I Gene Expression by Okadaic Acid in Cultured Rat Hepatocytes. Immenschuh, Stephan; Iwahara, Shin-Ichiro; Schwennen, Bianca // DNA & Cell Biology;Apr2002, Vol. 21 Issue 4, p347 

    Heme-binding protein 23 (HBP23), also termed peroxiredoxin I (Prx I), is an antioxidant protein that is induced by various oxidative stress stimuli. HBP23/Prx I has thioredoxin-dependent peroxidase activity and noncovalently binds the prooxidant heme with high affinity. To investigate the...

  • Biology of Heme in Health and Disease. Wijayanti, Nastiti; Katz, Norbert; Immenschuh, Stephan // Current Medicinal Chemistry;Apr2004, Vol. 11 Issue 8, p981 

    Heme is an essential molecule with contradictory biological functions. In hemoproteins such as hemoglobin and cytochromes protein-bound heme is a prosthetic group serving physiological functions as a transporter for oxygen and electrons. On the other hand free heme can have deleterious effects...

  • Heme-regulated eIF2a kinase (HRI) is required for translational regulation and survival of erythroid precursors in iron deficiency. Han, An-Ping; Yu, Channing; Lu, Linrong; Fujiwara, Yuko; Browne, Carol; Chin, Gregory; Fleming, Mark; Leboulch, Philippe; Orkin, Stuart H.; Chen, Jane-Jane // EMBO Journal;12/1/2001, Vol. 20 Issue 23, p6909 

    Although the physiological role of tissue-specific translational control of gene expression in mammals has long been suspected on the basis of biochemical studies, direct evidence has been lacking. Here, we report on the targeted disruption of the gene encoding the heme-regulated eIF2α kinase...

  • Butylated hydroxyanisole stimulates heme oxygenase-1 gene expression and inhibits neointima formation in rat arteries. Liu, Xiao-ming; Azam, Mohammed A.; Peyton, Kelly J.; Ensenat, Diana; Keswani, Amit N.; Wang, Hong; Durante, William // Cardiovascular Research;Apr2007, Vol. 74 Issue 1, p169 

    Abstract: Objective: Butylated hydroxyanisole (BHA) is a synthetic phenolic compound that is a potent inducer of phase II genes. Since heme oxygenase-1 (HO-1) is a vasoprotective protein that is upregulated by phase II inducers, the present study examined the effects of BHA on HO-1 gene...

  • Protective Effects of Heme-Oxygenase Expression in Cyclosporine A - Induced Injury. Rezzani, Rita; Rodella, Luigi; Bianchi, Rossella; Goodman, Alvin I.; Lianos, Elias A. // Current Neurovascular Research;Apr2005, Vol. 2 Issue 2, p157 

    Cyclosporine A (CsA) is the immunosuppressant of first choice in allotransplantation. Its use is associated with side effects of nephrotoxicity and neurotoxicity, which are among the most prominent. This study was undertaken to explore whether expression and activity of heme oxygenase (HO), the...

  • Gas biology: small molecular medicine. Semenza, Gregg; Prabhakar, Nanduri // Journal of Molecular Medicine;Mar2012, Vol. 90 Issue 3, p213 

    An introduction is presented in which the editor discusses various reports within the issue on topics including gene expression, oxygen delivery in red blood cells, and heme oxygenases.

  • Identification and Cloning of Differentially Expressed SOUL and ELIP Genes in Saffron Stigmas Using a Subtractive Hybridization Approach. Ahrazem, Oussama; Argandoña, Javier; Castillo, Raquel; Rubio-Moraga, Ángela; Gómez-Gómez, Lourdes // PLoS ONE;12/28/2016, Vol. 11 Issue 12, p1 

    Using a subtractive hybridization approach, differentially expressed genes involved in the light response in saffron stigmas were identified. Twenty-two differentially expressed transcript-derived fragments were cloned and sequenced. Two of them were highly induced by light and had sequence...

  • Adrenomedullin in Heart Failure: Molecular Mechanism and Therapeutic Implication. Nishikimi, Toshio; Nakao, Kazuwa; Kangawa, Kenji // Current Hypertension Reviews;Dec2011, Vol. 7 Issue 4, p273 

    Many neurohumoral factors play an important role in regulation of the cardiovascular system and in the pathophysiology of heart failure. Adrenomedullin (AM) is a potent long-lasting vasodilatory peptide that was discovered in acid extracts of human pheochromocytoma tissues. Both AM and its gene...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics