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Title: Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic

Abstract

Epidemiological studies link arsenic exposure to increased risks of cancers of the skin, kidney, lung, bladder and liver. Additionally, a variety of non-cancerous conditions such as diabetes mellitus, hypertension, and cardiovascular disease have been associated with chronic ingestion of low levels of arsenic. However, the biological and molecular mechanisms by which arsenic exerts its effects remain elusive. Here we report increased renal hexokinase II (HKII) expression in response to arsenic exposure both in vivo and in vitro. In our model, HKII was up-regulated in the renal glomeruli of mice exposed to low levels of arsenic (10 ppb or 50 ppb) via their drinking water for up to 21 days. Additionally, a similar effect was observed in cultured renal mesangial cells exposed to arsenic. This correlation between our in vivo and in vitro data provides further evidence for a direct link between altered renal HKII expression and arsenic exposure. Thus, our data suggest that alterations in renal HKII expression may be involved in arsenic-induced pathological conditions involving the kidney. More importantly, these results were obtained using environmentally relevant arsenic concentrations.

Authors:
; ;  [1]; ;  [2];  [3];  [4]
  1. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 E. Mabel Street, Tucson, AZ 85721 (United States)
  2. Department of Biomedical Engineering, University of Arizona, Tucson, AZ 85721 (United States)
  3. Department of Physiology, University of Arizona, Tucson, AZ 85721 (United States)
  4. Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 E. Mabel Street, Tucson, AZ 85721 (United States), E-mail: vaillancourt@pharmacy.arizona.edu
Publication Date:
OSTI Identifier:
21077811
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 224; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2007.06.019; PII: S0041-008X(07)00277-3; Copyright (c) 2007 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ARSENIC; BLADDER; DIABETES MELLITUS; DRINKING WATER; GLOMERULI; HEXOKINASE; HYPERTENSION; IN VITRO; IN VIVO; LIVER; LUNGS; MICE; NEOPLASMS; SKIN

Citation Formats

Pysher, Michele D., Sollome, James J., Regan, Suzanne, Cardinal, Trevor R., Hoying, James B., Brooks, Heddwen L., and Vaillancourt, Richard R. Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic. United States: N. p., 2007. Web. doi:10.1016/j.taap.2007.06.019.
Pysher, Michele D., Sollome, James J., Regan, Suzanne, Cardinal, Trevor R., Hoying, James B., Brooks, Heddwen L., & Vaillancourt, Richard R. Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic. United States. doi:10.1016/j.taap.2007.06.019.
Pysher, Michele D., Sollome, James J., Regan, Suzanne, Cardinal, Trevor R., Hoying, James B., Brooks, Heddwen L., and Vaillancourt, Richard R. 2007. "Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic". United States. doi:10.1016/j.taap.2007.06.019.
@article{osti_21077811,
title = {Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic},
author = {Pysher, Michele D. and Sollome, James J. and Regan, Suzanne and Cardinal, Trevor R. and Hoying, James B. and Brooks, Heddwen L. and Vaillancourt, Richard R.},
abstractNote = {Epidemiological studies link arsenic exposure to increased risks of cancers of the skin, kidney, lung, bladder and liver. Additionally, a variety of non-cancerous conditions such as diabetes mellitus, hypertension, and cardiovascular disease have been associated with chronic ingestion of low levels of arsenic. However, the biological and molecular mechanisms by which arsenic exerts its effects remain elusive. Here we report increased renal hexokinase II (HKII) expression in response to arsenic exposure both in vivo and in vitro. In our model, HKII was up-regulated in the renal glomeruli of mice exposed to low levels of arsenic (10 ppb or 50 ppb) via their drinking water for up to 21 days. Additionally, a similar effect was observed in cultured renal mesangial cells exposed to arsenic. This correlation between our in vivo and in vitro data provides further evidence for a direct link between altered renal HKII expression and arsenic exposure. Thus, our data suggest that alterations in renal HKII expression may be involved in arsenic-induced pathological conditions involving the kidney. More importantly, these results were obtained using environmentally relevant arsenic concentrations.},
doi = {10.1016/j.taap.2007.06.019},
journal = {Toxicology and Applied Pharmacology},
number = 1,
volume = 224,
place = {United States},
year = 2007,
month =
}
  • To clarify the pathophysiological mechanism underlying acute renal injury caused by acute exposure to arsenic, we subcutaneously injected both BALB/c and C57BL/6 mice with sodium arsenite (NaAs; 13.5 mg/kg). BALB/c mice exhibited exaggerated elevation of serum blood urea nitrogen (BUN) and creatinine (CRE) levels, compared with C57BL/6 mice. Moreover, half of BALB/c mice died by 24 h, whereas all C57BL/6 mice survived. Histopathological examination on kidney revealed severe hemorrhages, acute tubular necrosis, neutrophil infiltration, cast formation, and disappearance of PAS-positive brush borders in BALB/c mice, later than 10 h. These pathological changes were remarkably attenuated in C57BL/6 mice, accompanied withmore » lower intrarenal arsenic concentrations, compared with BALB/c mice. Among heavy metal inducible proteins including multidrug resistance-associated protein (MRP)-1, multidrug resistance gene (MDR)-1, metallothionein (MT)-1, and arsenite inducible, cysteine- and histidine-rich RNA-associated protein (AIRAP), intrarenal MDR-1, MT-1, and AIRAP gene expression was enhanced to a similar extent in both strains, whereas NaAs challenge augmented intrarenal MRP-1 mRNA and protein expression levels in C57BL/6 but not BALB/c mice. Moreover, the administration of a specific inhibitor of MRP-1, MK-571, significantly exaggerated acute renal injury in C57BL/6 mice. Thus, MRP-1 is crucially involved in arsenic efflux and eventually prevention of acute renal injury upon acute exposure to NaAs.« less
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  • A study was made of the ultramicroscopic features of the glomerulus and proximal tubule of the kidney of mice subjected to a single dose of x rays. A whole-body radiation with only 50 r was found to be sufficient to cause ultramicroscopic structural changes. The cellular damage in the foot cells was confined to the cytoplasm and could not be demonstrated by the 21st day. In the cells of the proximal tubule the lesion affected mainly the mitochondria (tendency to agglutination and fall in number of crests) and 3 weeks after treatment was still demonstrable, although to a lesser extentmore » (swelling of mitochondrial body). The changes, although reversible, are of some importance since they involve functionally significant renal elements. (auth)« less
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