Rapid, transient induction of ER stress in the liver and kidney after acute exposure to heavy metal: evidence from transgenic sensor mice.
Endoplasmic reticulum (ER) stress-responsive alkaline phosphatase (ES-TRAP) serves as a sensitive indicator for ER stress. In response to heavy metals including cadmium, nickel and cobalt, hepatocytes and renal tubular cells expressing ES-TRAP exhibited ER stress and decreased ES-TRAP activity. In ES-TRAP transgenic mice, acute exposure to cadmium showed rapid, transient decreases in the activity of serum ES-TRAP. It was inversely correlated with the induction of endogenous ER stress markers in the liver and kidney. Our result provides first evidence for the acute, reversible induction of ER stress in vivo after exposure to heavy metal.
Hiramatsu
Nobuhiko
N
Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo, Yamanashi 409-3898, Japan.
Kasai
Ayumi
A
Du
Shuqi
S
Takeda
Masayuki
M
Hayakawa
Kunihiro
K
Okamura
Maro
M
Yao
Jian
J
Kitamura
Masanori
M
D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000473:pathology*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D007700:Kinetics; D008099:Liver / Q000187:drug effects* / Q000201:enzymology; D019216:Metals, Heavy / Q000008:administration & dosage* / Q000633:toxicity*; D051379:Mice; D008822:Mice, Transgenic; D018832:Molecular Chaperones; D009928:Organ Specificity / Q000187:drug effects; D051381:Rats; D019284:Thapsigargin / Q000494:pharmacology; D013997:Time Factors; D023382:Toxicity Tests, Acute
D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D019216:Metals, Heavy; D018832:Molecular Chaperones; D019284:Thapsigargin; D000469:Alkaline Phosphatase