Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P05412 (c-Jun)
 11,453 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Expression of the c-Fos and c-Jun transcription factor was investigated by immunocytochemistry in the thalamus, hypothalamus, hippocampus and cortex of adult rats following intraperitoneal application of proconvulsant doses of the pyrethroid insecticides, cypermethrin and permethrin. Pyrethroid insecticides are used world-wide and their uptake, e.g., by nutrition and inhalation evokes severe neurological symptoms in animals and humans, but their effects on neuronal gene expression has not been elucidated. Cypermethrin induced a strong expression of c-Fos and c-Jun in all the thalamic nuclei, except the ventro-posterior complex and substantia nigra, and in all the hypothalamic nuclei. In general, the immunoreactivities (IR) persisted for 8 h on their maximal levels, and were still above control levels after 24 h in several thalamic and hypothalamic areas. c-Fos-IR was strongly increased in all cortical layers with a predominance in the superficial layers II-IV, whereas c-Jun-IR was only slightly increased. In the hippocampus, cypermethrin induced a weak expression of c-Fos, but not of c-Jun, in the dentate gyrus and CA-3 area. Permethrin that has a lower pharmacological potency, evoked a similar pattern of c-Fos and c-Jun expression, however, intensity and persistence of the neuronal labeling were less pronounced. Our results demonstrate that the neurotoxic effects of pyrethroid insecticides comprise molecular genetic alterations in the brain such as early and lasting induction of Fos and Jun transcription factor proteins. These changes in the neuronal program are prominent in the hypothalamus and thalamus that are involved in the regulation of the autonomic and visceral nervous systems.
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PMID:Systemic application of pyrethroid insecticides evokes differential expression of c-Fos and c-Jun proteins in rat brain. 885 38

Cypermethrin (CYM), a type II pyrethroid, is widely used as an insecticide for agriculture and household. Cumulative evidence indicates that acute and chronic exposure to CYM might cause a number of health problems, such as cancer and neuronal system diseases. However, the molecular mechanism underlying this pathology is not known. The main objective of this study was to define the effects of CYM on macrophages and the implication of such effects in cancer metastasis and the potential mechanism involved. The effects of CYM on the macrophages were evaluated by detecting the expression of M1 and M2 macrophage polarization markers through ELISA, quantitative RT-PCR, and Western blot assay. Transwell and wound healing assays were used to test the migration of lung cancer cells after exposure to CYM in vitro and a metastasis animal model in vivo. Treatment with CYM significantly suppressed lipopolysaccharide (LPS)-induced M1 macrophage polarization and promoted a shift toward M2 macrophage status. Mechanistically, CYM downregulated miR-155 significantly, leading to enhanced expression of its target gene Bcl6, thereby reducing the expression of mitogen-activated protein kinase 4 (MKK4), an upstream kinase of c-Jun N-terminal kinases (JNK), and inhibiting JNK activation. Impaired JNK activation thus promoted a shift in macrophage polarization from the M1 to the M2 phenotype. Finally, CYM-treated macrophages promoted metastasis of Lewis lung cancer cells in both in vitro and in vivo models. Taken together, our findings show that CYM is able to inhibit the M1 polarization and promote the macrophages to the M2 phenotype, which plays an important role in tumor metastasis.
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PMID:Cypermethrin Promotes Lung Cancer Metastasis via Modulation of Macrophage Polarization by Targeting MicroRNA-155/Bcl6. 2947 34