Role of Polyphenols and Transient Receptor Potential Canonical 3 Channel (TRPC3) on Manganese-Induced Astrocyte Toxicity
Location
Georgia
Start Date
16-5-2017 1:00 PM
Description
INTRODUCTION: Polyphenols, Epigallocatechin (EGC), Epigallocatechin-3-Gallate (EGCG), and Myricetin (MRC) are involved in natural preventative care. In metal neurotoxicity, these mechanisms are not clearly identified. Manganese (Mn) is a trace element, but is toxic at higher concentrations from occupational and/or environmental exposures. Astrocytes play a vital role in neuronal signaling. When exposed to toxins, astrocytes undergo astrogliosis, characterized by increased production of glial fibrillary acidic protein (GFAP). The Transient Receptor Potential Canonical 3 channel (TRPC3) is known to influence calcium (Ca) flux of cortical astrocytes needed for signaling, though Mn has been shown to block TRPC3. In this study, we have revealed the presence of TRPC3 on hippocampal astrocytes and the effect of polyphenols on TRPC3 regulation, GFAP production, and viability of Mn-induced astrocyte toxicity.
METHODS: Astrocytes (E18) were isolated from hippocampal tissue and cultured for 12 days. Cells were plated with 1, 3, and 10uM of EGC, EGCG, and MRC, incubated for 24 hours. Mn (100uM) was added to wells, incubated for 48 hours. WST-8 detected cell viability and immunofluorescence identified GFAP and TRPC3.
RESULTS: Immunofluorescence indicated the presence of TRPC3 channel on hippocampal astrocytes. WST-8 showed consistent decreased viability when Mn was added to cells. Increased GFAP confirmed that Mn caused damage to astrocytes. EGC (3uM), EGCG (1uM), MRC (1uM) appeared to decrease GFAP and TRPC3.
DISCUSSION: For the first time, TRPC3 channel was demonstrated on hippocampal astrocytes. The regulation of TRPC3 in Mn toxicity is not clear, though literature suggests that the channel is upregulated because astrocytic Ca signals are needed to initiate astrogliosis. EGC (10uM) and MRC (3uM) may prevent damage produced by Mn.
CONCLUSION: TRPC3 is present on hippocampal astrocytes. Certain concentrations of polyphenols may be astroprotective against Mn-induced damage.
Embargo Period
6-20-2017
Role of Polyphenols and Transient Receptor Potential Canonical 3 Channel (TRPC3) on Manganese-Induced Astrocyte Toxicity
Georgia
INTRODUCTION: Polyphenols, Epigallocatechin (EGC), Epigallocatechin-3-Gallate (EGCG), and Myricetin (MRC) are involved in natural preventative care. In metal neurotoxicity, these mechanisms are not clearly identified. Manganese (Mn) is a trace element, but is toxic at higher concentrations from occupational and/or environmental exposures. Astrocytes play a vital role in neuronal signaling. When exposed to toxins, astrocytes undergo astrogliosis, characterized by increased production of glial fibrillary acidic protein (GFAP). The Transient Receptor Potential Canonical 3 channel (TRPC3) is known to influence calcium (Ca) flux of cortical astrocytes needed for signaling, though Mn has been shown to block TRPC3. In this study, we have revealed the presence of TRPC3 on hippocampal astrocytes and the effect of polyphenols on TRPC3 regulation, GFAP production, and viability of Mn-induced astrocyte toxicity.
METHODS: Astrocytes (E18) were isolated from hippocampal tissue and cultured for 12 days. Cells were plated with 1, 3, and 10uM of EGC, EGCG, and MRC, incubated for 24 hours. Mn (100uM) was added to wells, incubated for 48 hours. WST-8 detected cell viability and immunofluorescence identified GFAP and TRPC3.
RESULTS: Immunofluorescence indicated the presence of TRPC3 channel on hippocampal astrocytes. WST-8 showed consistent decreased viability when Mn was added to cells. Increased GFAP confirmed that Mn caused damage to astrocytes. EGC (3uM), EGCG (1uM), MRC (1uM) appeared to decrease GFAP and TRPC3.
DISCUSSION: For the first time, TRPC3 channel was demonstrated on hippocampal astrocytes. The regulation of TRPC3 in Mn toxicity is not clear, though literature suggests that the channel is upregulated because astrocytic Ca signals are needed to initiate astrogliosis. EGC (10uM) and MRC (3uM) may prevent damage produced by Mn.
CONCLUSION: TRPC3 is present on hippocampal astrocytes. Certain concentrations of polyphenols may be astroprotective against Mn-induced damage.