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Effects of PQ's cytotoxicity on secretory vesicles in astroglia: Expression alternation of secretogranin II and its potential interaction with intracellular factors
- Source :
- Biochemical and Biophysical Research Communications. 497:675-682
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 2018.
-
Abstract
- It has been extensively characterized that paraquat (PQ) selectively targets to the substantia nigra and exerts neurotoxic actions on dopaminergic neurons. However, a little knowledge is available about astroglia in PQ exposure, especially its complex secretory machinery. To explore this point, we built up a PQ-induced model in cultural U118 astrocyte. Since the granin family is considered as a master regulator of cargo sorting and large dense core vesicles (LDCVs) biogenesis in the regulated secretory pathway of nervous and neuroendocrine cells, the current study focused on one member, secretogranin II (SCG2) and investigated its alternation and potential relationship with other astrocyte-derived factors under PQ insult. We found that PQ upregulated SCG2 expression on both RNA and protein levels and stimulated the mRNA expression of neurotrophic factors, cytokines and glutamine synthetase (GS) simultaneously. RNAi knockdown of SCG2 did not rescue the cell cycle arrest induced by PQ but affected expressions of IL-6 and GS on mRNA and protein levels. Further studies on subcellular location showed that SCG2-positive secretory granules were partially colocalized with IL-6 but not GS in PQ exposure astrocyte. Taken together, our findings indicate that the expression alternation of SCG2 under astroglial activation by PQ may be necessary compensation for cargo sorting and LDCV biogenesis. The involvement of the IL-6 and GS suggests that the SCG2 may potentially regulate inflammatory factors and excitatory neurotransmitter to the cytotoxicity of PQ on astroglia.
- Subjects :
- Paraquat
0301 basic medicine
Cell Survival
Biophysics
Substantia nigra
Biochemistry
03 medical and health sciences
0302 clinical medicine
RNA interference
Neurotrophic factors
Cell Line, Tumor
medicine
Humans
Protein Interaction Maps
Molecular Biology
Messenger RNA
Gene knockdown
Herbicides
Chemistry
Cell Cycle
Granin
Cell Biology
Up-Regulation
Cell biology
030104 developmental biology
medicine.anatomical_structure
Secretogranin II
Astrocytes
030217 neurology & neurosurgery
Intracellular
Astrocyte
Subjects
Details
- ISSN :
- 0006291X
- Volume :
- 497
- Database :
- OpenAIRE
- Journal :
- Biochemical and Biophysical Research Communications
- Accession number :
- edsair.doi.dedup.....770e7f5f89d5469fb0c6172ec0750de6