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Chromium (VI) induces antioxidant gene HO-1 by activating the CNC BZIP transcription factor NRF2.

Authors
He-X; Lin-G; Zhang-J; Ma-Q
Source
Toxicologist 2006 Mar; 90(1):419
NIOSHTIC No.
20029921
Abstract
Chromium, a transition metal element abundantly present in the earth's crust, is widely used in industrial processes. Occupational exposure to Cr (VI)-containing compounds is known to cause multi-organ toxicity including renal damage, allergy and asthma, and cancer of the respiratory tract in humans. The molecular mechanism by which chromium elicits its biological effects is currently unclear but may involve the formation of reactive intermediates, oxidant stress, and gene induction. Here, we report that Cr (VI) induces antioxidant gene HO-1 at both mRNA and protein levels in hepa1c1c7 cells. Expression of a dominant negative form of Nrf2, a cap 'n' collar basic leucine zipper transcription factor, in the cells blocks the induction by Cr (VI), implicating Nrf2 as the key transcription factor in the induction. Mechanistic analysis reveals that Cr (VI) increases the protein but not the mRNA level of Nrf2 as well as the nuclear accumulation of the protein. Cr (VI) does not affect the protein levels of Keap1, which is a repressor of the cytoplasmic Nrf2, or Cul-3, an E3 ligase involved in proteasomal degradation of Nrf2. These results provide the first evidence that Cr (VI) induces antioxidant gene HO-1 important in ROS defense by activating Nrf2. The study offers a model in which transcriptional gene regulation by Cr (VI) can be analyzed at molecular levels.
Keywords
Chromium-compounds; Antioxidants; Antioxidation; Genes; Occupational-exposure; Cancer; Respiratory-system-disorders; Bronchial-asthma; Allergies; Biological-effects; Proteins
CAS No.
7440-47-3
Publication Date
20060301
Document Type
Abstract
Fiscal Year
2006
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
1096-6080
NIOSH Division
HELD
Source Name
The Toxicologist. Society of Toxicology 45th Annual Meeting and ToxExpo, March 5-9, 2006, San Diego, California
State
WV; MA
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