About: Cadmium Induction Pathway

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Attributes	Values
rdf:type	Class
rdfs:label	Cadmium Induction Pathway
rdfs:subClassOf	Regulatory Pathway
Semantic_Type	Functional Concept
Preferred_Name	Cadmium Induction Pathway
UMLS_CUI	C1511475
BioCarta_ID	h_cdMacPathway
ALT_DEFINITION	Exposure to divalent cadmium ions (Cd2+) is a known cancer risk factor, but the molecular mechanisms responsible for the inappropriate induction of cellular proliferation by cadmium are still being figured out. One cellular model used to study this process is macrophages grown in culture. In cultured macrophages, cadmium acts both at the cell surface and in the cytoplasm to induce proliferation. At the cell surface, cadmium interacts with a pertussis-sensitive cell surface receptor, probably a Gi-coupled GPCR, to stimulate proliferation. Cadmium can enter cells through calcium ion channels and once in cells affects calcium release by the ER. In addition to changes in intracellular calcium, the proliferative effects of cadmium are mediated by the Ras/Map kinase pathway, and also NF-kB. Inhibition of phospholipase C, map kinases, or NF-kB with a variety of pharmacological inhibitors all blocked the activation of cellular proliferation by cadmium. Protein kinase C is also activated by cadmium, upstream of the Map kinase pathway. Changes in transcription induced by cadmium include induction of immediate early genes like fos, jun, and myc. In addition to inducing cellular proliferation, cadmium also is slightly genotoxic due to inhibition of DNA repair, activates stress genes, and inhibits the immune system. The immunomodulatory effects observed with cadmium treatment may also involvement transcriptional disregulation, including the expression of cytokines such as IL-4, IL-10, and TNF-alpha. Although macrophages have been used for many studies, other cell types are also the target of cadmium's toxicity.BIOCARTA
Legacy_Concept_Name	Cadmium_Induction_Pathway
FULL_SYN	Cadmium Induction PathwayPTNCI Cadmium induces DNA synthesis and proliferation in macrophagesPTBIOCARTA
code	C39023
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