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2.25 - Heavy Metal-Regulated Gene Expression

Qian, Yongchang

Comprehensive Toxicology, Chapter 2.25, pp.495-521

ISBN: 978-0-08-046868-6 ; ISBN: 978-0-08-046884-6 ; DOI: 10.1016/B978-0-08-046884-6.00226-8

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  • Nhan đề:
    2.25 - Heavy Metal-Regulated Gene Expression
  • Tác giả: Qian, Yongchang
  • Chủ đề: astroglia ; copper ; development ; gene expression ; heavy metal ; lead ; molecular chaperone ; nervous system ; neurons ; neurotoxicity ; oligodendroglia ; protein kinase C ; signaling ; transcription ; transcription factor
  • Là 1 phần của: Comprehensive Toxicology, Chapter 2.25, pp.495-521
  • Mô tả: Toxic heavy metals (e.g., lead) are an important category of carcinogens as well as environmental neurotoxicants showing a significant developmental neurotoxicity in pediatric populations. Evidence from numerous epidemiologic studies, animal studies, and cell culture studies demonstrates that heavy metal lead can alter cell signaling by direct regulation of gene expression through transcription factors (e.g., Sp1) or indirect regulation of gene expression through protein kinase C (PKC), copper homeostasis, and molecular chaperone (e.g., 78kDa glucose-regulated protein (GRP78)), leading to alteration (e.g., delayed or precocious) of developmental progress in the nervous system. The alteration contributes to decline of neurophysiological performance in children and onset of neurologic disorders, including Alzheimer’s disease, in the late life. Since different brain cells including neurons, oligodendroglia, and astroglia have differential expression patterns of lead molecular targets, they have cell type-specific responses to heavy metal lead. Meanwhile, based on development of blood–brain barrier and cytoarchitecture of the nervous system, lead exerts its neurotoxicity by targeting different brain cells during different stages of development. Although lead-induced gene expression plays an important role in alterations of the nervous system development, which is highly linked to impaired neurophysiological performance and neurologic disorders, mechanisms need to be finely defined. It is extremely important to accurately determine the intracellular concentration of free lead ions in cell cultures and cell type-specific lead levels in animals when lead-induced gene expression is correlated to dosage.
  • Nơi xuất bản: Elsevier Ltd
  • Năm xuất bản: 2010
  • Ngôn ngữ: English
  • Số nhận dạng: ISBN: 978-0-08-046868-6 ; ISBN: 978-0-08-046884-6 ; DOI: 10.1016/B978-0-08-046884-6.00226-8

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