Hemin is Transported in Human Leukemia K562 Cells and Interacts with DNA Sequences

Tsiftsoglou, Asterios S.; Tsamadou, Athina I.; Robinson, Stephen H.; Wong, Willie

doi:10.1007/978-3-642-84613-7_9

Cited by 4 publications

(8 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Many morphological and functional changes have been reported in differentiated HL‐60 cells, including generation of superoxide [24], reassembly of the cytoskeleton [25], decrease of RNA synthesis [26,27], formation of chromatin sheets [28], and alterations of enzyme metabolism [29,30]. These changes might be the reason why differentiated HL‐60 cells became resistant to RC‐RNase.…”

Section: Discussionmentioning

confidence: 99%

Induction of differentiation rescues HL‐60 cells from Rana catesbeiana ribonuclease‐induced cell death

Wei

Tang

et al. 2002

FEBS Letters

View full text Add to dashboard Cite

Rana catesbeiana ribonuclease (RC-RNase) exerted strong anti-tumor activity and its cytotoxicity was shown to correlate with di¡erentiation stages of three di¡erent hepatoma cell lines. In this study, we demonstrate di¡erent RC-RNase cytotoxicity in undi¡erentiated HL-60 cells and in those that had been induced to di¡erentiate by retinoic acid or dimethylsulfoxide. RC-RNase showed cytotoxicity in undi¡erentiated HL-60 cells, but not in HL-60 cells undergoing terminal di¡er-entiation. Furthermore, the caspase-9/caspase-3 pathway was activated when RC-RNase induced death in undi¡erentiated HL-60 cells and induction of di¡erentiation led to a reversal of the caspase activation pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Induction of differentiation rescues HL‐60 cells from Rana catesbeiana ribonuclease‐induced cell death

Wei

Tang

et al. 2002

FEBS Letters

View full text Add to dashboard Cite

show abstract

“…Parts of the findings described above (communicated as preliminary data in meetings elsewhere (A. I. Tsamadou et al, 1992;A. S. Tsiftsoglou et al, 1993), have indicated that K562 cells contain proteins that interact selectively with radiolabeled hemin and facilitate its intracellular distribution and other biological functions in the cells.…”

Section: Detection Of Cytoplasmic Protein Complexes With [ 59 Fe]-lab...mentioning

confidence: 93%

Hemin accumulation and identification of a heme‐binding protein clan in K562 cells by proteomic and computational analysis

Tsolaki

Georgiou-Siafis

Tsamadou

et al. 2021

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Heme (iron protoporphyrin IX) is an essential regulator conserved in all known organisms. We investigated the kinetics of intracellular accumulation of hemin (oxidized form) in human transformed proerythroid K562 cells using [ 14 C]-hemin and observed that it is time and temperature-dependent, affected by the presence of serum proteins, as well as the amphipathic/hydrophobic properties of hemin. Hemin-uptake exhibited saturation kinetics as a function of the concentration added, suggesting the involvement of a carrier-cell surface receptormediated process. The majority of intracellular hemin accumulated in the cytoplasm, while a substantial portion entered the nucleus. Cytosolic proteins isolated by hemin-agarose affinity column chromatography (HACC) were found to form stable complexes with [ 59 Fe]-hemin. The HACC fractionation and Liquid chromatography-mass spectrometry analysis of cytosolic, mitochondrial, and nuclear protein isolates from K562 cell extracts revealed the presence of a large number of hemin-binding proteins (HeBPs) of diverse ontologies, including heat shock proteins, cytoskeletal proteins, enzymes, and signaling proteins such as actinin a4, mitogen-activated protein kinase 1 as well as several others. The subsequent computational analysis of the identified HeBPs using HemoQuest confirmed the presence of various hemin/heme-binding motifs [C(X)nC, H, Y] in their primary structures and conformations. The possibility that these HeBPs contribute to a heme intracellular trafficking protein network involved in the homeostatic regulation of the pool and overall functions of heme is discussed.

show abstract

“…80 84 The precise mechanism by which hemin acts as an inducer is unclear; however, it has been suggested that hemin, a lipophilic compound, diffuses into K562 cells readily and binds to intracellular and nuclear proteins called hemin binding proteins. 85 Once in the nucleus, hemin modulates the interactions of known transcriptional factors like NF-E2, Oct-1, and GATA-1 by acting selectively on the -globin gene promoter. 86 Hemin-induced erythroid differentiation of K562 cells, therefore, represents an important in vitro model for basic studies of human erythropoiesis.…”

Section: Erythroid Differentiation Model Using Erythroleukemic Cell Lmentioning

confidence: 99%

Mechanisms of Erythropoietic Failure in Shwachman Diamond Syndrome Caused by Loss of Ribosome-Related Protein SBDS.

Sen

Wang

Adams

et al. 2009

Blood

View full text Add to dashboard Cite

3203 Poster Board III-140 Anemia occurs in 60% of patients with Shwachman Diamond Syndrome (SDS). Although bi-allelic mutations in SBDS cause SDS, it is unclear whether SBDS is critical for erythropoiesis and what the pathogenesis of anemia is in SDS. We hypothesize that SBDS protects early erythroid progenitors from apoptosis by promoting ribosome biosynthesis and translation. During early erythroid differentiation of human K562 cells and primary CD133+ cells, a prominent upregulation of SBDS by RT-qPCR was found. SBDS deficiency by vector-based shRNA led to impaired cell expansion of differentiating K562 cells due to accelerated apoptosis and a mild reduction in proliferation. Furthermore, the cells showed general reduction of 40S, 60S, 80S ribosomal subunits, loss of polysomes and impaired global translation during differentiation. Both cell expansion and translation defects were rescued upon re-introduction of SBDS in K562 cells. Interestingly, leucine partly corrected the cell expansion and translational defects of non-differentiating SBDS-deficient K562 cells, while differentiating SBDS-deficient K562 cells showed improved cell expansion in the presence of additional translation stimulators such as IGF-1. SBDS-knockdown CD133+ cells showed increased BFU-E colony formation under conditions with leucine and a combination of leucine and IGF-1 treatment. Although the erythroid cell expansion defect in K562 cells is independent of p53 as these cells do not express the gene, an upregulation of TAp73, was found in resting SBDS deficient K562 cells. However expression of TAp73 was lost during differentiation. DNp63 was also not upregulated in SBDS-deficient K562 erythroid cells. These results demonstrate that the role of SBDS in non-differentiated cells versus differentiated cells represents two dynamic scenarios and that SBDS plays a critical role in erythroid expansion by promoting survival of early erythroid progenitors and in maintaining ribosome biogenesis during erythroid maturation through a pathway independent of p53 family members. Disclosures No relevant conflicts of interest to declare.

show abstract

Hemin is Transported in Human Leukemia K562 Cells and Interacts with DNA Sequences

Cited by 4 publications

References 20 publications

Induction of differentiation rescues HL‐60 cells from Rana catesbeiana ribonuclease‐induced cell death

Induction of differentiation rescues HL‐60 cells from Rana catesbeiana ribonuclease‐induced cell death

Hemin accumulation and identification of a heme‐binding protein clan in K562 cells by proteomic and computational analysis

Mechanisms of Erythropoietic Failure in Shwachman Diamond Syndrome Caused by Loss of Ribosome-Related Protein SBDS.

Contact Info

Product

Resources

About