Increased hexokinase II expression in the renal glomerulus of mice in response to arsenic.
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.
Pysher
Michele D
MD
Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, 1703 E. Mabel Street, Tucson, AZ 85721, USA.
Sollome
James J
JJ
Regan
Suzanne
S
Cardinal
Trevor R
TR
Hoying
James B
JB
Brooks
Heddwen L
HL
Vaillancourt
Richard R
RR
D000818:Animals; D001151:Arsenic / Q000633:toxicity*; D002460:Cell Line; D002478:Cells, Cultured; D005455:Fluorescent Antibody Technique; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D006593:Hexokinase / Q000096:biosynthesis* / Q000652:urine; D015151:Immunoblotting; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007672:Kidney Cortex / Q000187:drug effects / Q000378:metabolism; D007678:Kidney Glomerulus / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D012313:RNA / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation / Q000187:drug effects; D014867:Water
D014867:Water; D012313:RNA; D006593:Hexokinase; D001151:Arsenic