NAD(P)H:quinone Oxidoreductase 1-Compromised Human Bone Marrow Endothelial Cells Exhibit Decreased Adhesion Molecule Expression and CD34+ Hematopoietic Cell Adhesion

Zhou, Hongfei; Dehn, Donna L.; Kepa, Jadwiga K.; Siegel, David; Scott, Devon; Tan, Wei; Ross, David

doi:10.1124/jpet.110.167841

Cited by 12 publications

(15 citation statements)

References 36 publications

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“…Studies showed that benzene causes hematotoxic effects, even at exposure levels lower than 1 ppm [4,5,6]. Benzene metabolites interact with hematopoietic cells at different differentiation stages in bone marrow (BM) [7], resulting in genetic [8], chromosomal, or epigenetic abnormalities [9,10], genomic instability [11], and altered proliferation and differentiation of hematopoietic stem cells (HSCs) [12], leading to the formation of mutated hematopoietic cells and subsequent clonal evolution to leukemia [13]. Although many epidemiological and experimental studies have been carried out, the mechanisms of benzene-induced hematotoxicity remain to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Sun

Cao

Zhang

et al. 2016

IJERPH

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Abstract:Benzene is a well-known hematotoxic carcinogen that can cause leukemia and a variety of blood disorders. Our previous study indicated that benzene disturbs levels of metabolites in the fatty acid β-oxidation (FAO) pathway, which is crucial for the maintenance and function of hematopoietic and leukemic cells. The present research aims to investigate the effects of benzene on changes in the expression of key enzymes in the FAO pathway in male C3H/He mice. Results showed that benzene exposure caused reduced peripheral white blood cell (WBC), red blood cell (RBC), platelet (Pit) counts, and hemoglobin (Hgb) concentration. Investigation of the effects of benzene on the expression of FA transport-and β-oxidation-related enzymes showed that expression of proteins Cpt1a, Crat, Acaa2, Aldh1l2, Acadvl, Crot, Echs1, and Hadha was significantly increased. The ATP levels and mitochondrial membrane potential decreased in mice exposed to benzene. Meanwhile, reactive oxygen species (ROS), hydrogen peroxide (H 2 O 2 ), and malondialdehyde (MDA) levels were significantly increased in the benzene group. Our results indicate that benzene induces increased expression of FA transport and β-oxidation enzymes, mitochondrial dysfunction, and oxidative stress, which may play a role in benzene-induced hematotoxicity.

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Section: Introductionmentioning

confidence: 99%

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Sun

Cao

Zhang

et al. 2016

IJERPH

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“…Similarly, no differences were observed in levels of nuclear NFκB p65 in HBMEC as a function of inhibition or knockdown of NQO1. However, we did observe decreased nuclear levels of NFκB phospho-p65, phospho-c-Jun and ATF2 in HBMEC after compromising NQO1 [42] and all of these signaling systems have been shown to play a role in TNF-α induced gene expression [43,45–47]. These observations provide a potential mechanistic link between altered adhesion in NQO1-compromised endothelial cells and nuclear levels of key transcription factors.…”

Section: Signaling Events Modulated By Compromising Nqo1 In Hbmecmentioning

confidence: 76%

“…We therefore examined the effects of compromising NQO1 either pharmacologically or genetically on adhesion molecule expression in HBMEC after TNF-α stimulation. TNF-α led to increased expression of E-selectin, VCAM-1 and ICAM-1 in HBMEC and either pre-treatment with inhibitors of NQO1 or anti-NQO1 siRNA resulted in a marked reduction of adhesion molecule expression in HBMEC [42]. …”

Section: Nqo1 and Bone Marrow Endotheliummentioning

confidence: 99%

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Benzene toxicity: The role of the susceptibility factor NQO1 in bone marrow endothelial cell signaling and function

Ross¹,

Zhou²,

Siegel³

2011

Chemico-Biological Interactions

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The homozygous NQO1*2 polymorphism results in a null NQO1 phenotype and is a susceptibility factor for occupational benzene poisoning. NQO1 plays an important role in detoxification of benzene-derived quinones but plays a role in numerous other non-metabolic cellular functions. NQO1 is expressed in endothelial cells of bone marrow which form the vascular stem cell niche important in stem cell homing and mobilization. We therefore employed a transformed human bone marrow endothelial cell (HBMEC) line to define the effects of compromising NQO1 on endothelial function. Either inhibition or knockdown of NQO1 led to decreased expression of the adhesion molecules E-selectin, VCAM-1 and ICAM-1 and decreased functional adhesion of CD34+ progenitor cells after TNFα stimulation. Suicide inhibition or knockdown of NQO1 decreased NFκB p105 precursor and NFκB p50 subunit levels as well as leading to decreased nuclear levels of NFκB phospho-p65. An additional function of endothelial cells is tube formation and angiogenesis which was inhibited by the benzene metabolite hydroquinone suggesting that endothelial function may be affected at multiple levels after exposure of NQO1*2 polymorphic individuals to benzene. These data demonstrate that NQO1 plays an upstream role in NFκB signaling and adhesion molecule expression in HBMEC and that NQO1 has important regulatory effects in its own right in addition to being a marker for Nrf-2 activation. Metabolic susceptibility factors such as NQO1 have roles in addition to detoxification of reactive intermediates and interrogation of these novel roles can inform both mechanisms of toxicity and human risk assessment.

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“…A study demonstrated that inhibition or knockdown of NQO1 in human bone marrow endothelium leads to decreased TNF- α -induced adhesion molecule expression and adhesion of progenitors to endothelial cells via an NF- κ B mechanism [37]. …”

Section: Introductionmentioning

confidence: 99%

Cytokine Network Involvement in Subjects Exposed to Benzene

Minciullo

Navarra

Calapai

et al. 2014

Journal of Immunology Research

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Benzene represents an ubiquitous pollutant both in the workplace and in the general environment. Health risk and stress posed by benzene have long been a concern because of the carcinogenic effects of the compound which was classified as a Group 1 carcinogen to humans and animals. There is a close correlation between leukemia, especially acute myeloid leukemia, and benzene exposure. In addition, exposure to benzene can cause harmful effects on immunological, neurological, and reproductive systems. Benzene can directly damage hematopoietic progenitor cells, which in turn could lead to apoptosis or may decrease responsiveness to cytokines and cellular adhesion molecules. Alternatively, benzene toxicity to stromal cells or mature blood cells could disrupt the regulation of hematopoiesis, including hematopoietic commitment, maturation, or mobilization, through the network of cytokines, chemokines, and adhesion molecules. Today there is mounting evidence that benzene may alter the gene expression, production, or processing of several cytokines in vitro and in vivo. The purpose of this review was to systematically analyze the published cases of cytokine effects on human benzene exposure, particularly hematotoxicity, and atopy, and on lungs.

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NAD(P)H:quinone Oxidoreductase 1-Compromised Human Bone Marrow Endothelial Cells Exhibit Decreased Adhesion Molecule Expression and CD34+ Hematopoietic Cell Adhesion

Cited by 12 publications

References 36 publications

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Benzene Exposure Alters Expression of Enzymes Involved in Fatty Acid β-Oxidation in Male C3H/He Mice

Benzene toxicity: The role of the susceptibility factor NQO1 in bone marrow endothelial cell signaling and function

Cytokine Network Involvement in Subjects Exposed to Benzene

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