基礎講座 電気泳動(Electrophoresis)

Metallothioneins are cysteine-rich, small metal-binding proteins present in various mammalian tissues. Of the four common metallothioneins, MT-1 and MT-2 (MTs) are expressed in most tissues, MT-3 is predominantly present in brain, whereas MT-4 is restricted to the squamous epithelia. The expression of MT-1 and MT-2 in some organs exhibits sex, age, and strain differences, and inducibility with a variety of stimuli. In adult mammals, MTs have been localized largely in the cell cytoplasm, but also in lysosomes, mitochondria and nuclei. The major physiological functions of MTs include homeostasis of essential metals Zn and Cu, protection against cytotoxicity of Cd and other toxic metals, and scavenging free radicals generated in oxidative stress. The role of MTs in Cd-induced acute and chronic toxicity, particularly in liver and kidneys, is reviewed in more details. In acute toxicity, liver is the primary target, whereas in chronic toxicity, kidneys are major targets of Cd. The intracellular MTs bind Cd ions and form CdMT. In chronic intoxication, Cd stimulates de novo synthesis of MTs; it is assumed that toxicity in the cells starts when loading with Cd ions exceeds the buffering capacity of intracellular MTs. CdMT, released from the Cd-injured organs, or when applied parenterally for experimental purposes, reaches the kidneys via circulation, where it is filtered, endocytosed in the proximal tubule cells, and degraded in lysosomes. Liberated Cd can immediately affect the cell structures and functions. The resulting proteinuria and CdMT in the urine can be used as biomarkers of tubular injury.

Role of metallothionein in cadmium traffic and toxicity in kidneys and other mammalian organs.

Even though normal exposure levels to Cd may be small, the human body is inefficient at excreting the heavy metal, so it slowly accumulates over the period of a lifetime. Eventually, the Cd level in the body may become toxic and give rise to harmful effects. Cadmium exposure could therefore be linked to diseases associated with aging such as osteoporosis, prostate cancer, and pancreatic cancer. These potential links have driven the development of a myriad of analytical techniques for the determination of Cd in biological samples. Natural biological Cd concentrations are typically low, so preconcentration steps and sensitive instruments are frequently a necessity. In addition, the complex matrices of biological specimens such as blood, urine, serum, and tissue often require a form of matrix modification or separation. This review provides an overview of these methods with 200 references from the literature published between 1995 and 2005. The analytical methods for the determination of Cd in biolo...

Determination of Cadmium in Biological Samples

Metallothioneins (MTs) are a group of low molecular mass,
cysteine-rich proteins with a variety of functions including
involvement in metal homeostasis, free radical scavenging,
protection against heavy metal damage, and metabolic regulation
via Zn donation. The overexpression of MTs in proliferating
cells is turning the attention to the study of MTs as novel
promising marker of tumor diseases. Besides, levels of MTs in
invertebrates and aquatic vertebrates well correlate with heavy
metal pollution of an environment and, thus, serve as
bio-environmental marker. It is not surprising that these
proteins are of great interest not only for biochemists,
molecular biologists clinical chemists, but also for
environmental chemists and ecologists. Detection and
quantification of MTs, which is needed in all above mentioned
areas, is challenging due to the high cysteine content and
relatively low molecular mass. This review is giving an
overview of the analytical methods used for determination of
MTs comprising a broad range of immunochemical, electrochemical
as well as spectrometric methods, which have been optimized and
even hyphenated with different separation methods to detect
MTs. More attention is paid to the structural analysis of these
proteins as well as the employment of analytical instruments
for environmental, biochemical and clinical purposes.

/pdf/analytical-methods-for-metallothionein-detection-4dqtfbjo51.pdf

Analytical Methods for Metallothionein Detection

Element speciation analysis using capillary electrophoresis: twenty years of development and applications.

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