Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P43026 (
lipopolysaccharide
)
62,215
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Environmental neurotoxins such as paraquat (PQ), manganese, and 1-1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) are associated with a higher risk of Parkinson's disease (PD). These parkinsonian toxins exert certain common toxicological effects on astroglia; however, their role in the regulatory functions of astroglial secretory proteins remains unclear. In a previous study, we observed that secretogranin II (SCG2) and secretogranin III (
SCG3
), which are important components of the regulated secretory pathway, were elevated in PQ-activated U118 astroglia. In the current study, we used the parkinsonian toxins dopamine (DA), active metabolite of MPTP (MPP
+
), MnCl
2
, and
lipopolysaccharide
(
LPS
) as inducers, and studied the potential regulation of SCG2 and
SCG3
. Our results showed that all the parkinsonian toxins except
LPS
affected astroglial viability but did not cause apoptosis. Exposure to DA, MPP
+
, and MnCl
2
upregulated glial fibrillary acidic protein (GFAP), a marker for astrocyte activation, and stimulated the levels of several astrocytic-derived factors. Further, DA, MPP
+
, and MnCl
2
exposure impeded astroglial cell cycle progression. Moreover, the expression of
SCG3
was elevated, while its exosecretion was inhibited in astroglia activated by parkinsonian toxins. The level of SCG2 remained unchanged. In combination with our previous findings, the results of this study indicate that
SCG3
may act as a cofactor in astrocyte activation stimulated by various toxins, and the regulation of
SCG3
could be involved in the toxicological mechanism by which parkinsonian toxins affect astroglia.
...
PMID:Secretogranin III upregulation is involved in parkinsonian toxin-mediated astroglia activation. 3240 59
