Functional restoration of lysosomes and mitochondria through modulation of AKT activity ameliorates senescence

Kuk, Myeong Uk; Lee, Haneur; Song, Eun Seon; Lee, Yun Haeng; Park, Ji Yun; Jeong, Subin; Kwon, Hyung Wook; Byun, Youngjoo; Park, Sang Chul; Park, Taezoon

doi:10.1016/j.exger.2023.112091

Cited by 5 publications

(1 citation statement)

References 46 publications

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“…Further investigation of AKT3 is its ability to modulate mitochondria and autophagy has been reported [ 75 , 76 ]. Most importantly, AKT3 has been shown to be involved in lysosomal dysregulation caused by cellular senescence [ 77 ]. Dubois et al, 2019 [ 72 ] showed that AKT3 modulates protection against demyelinating inflammatory disorder.…”

Section: Discussionmentioning

confidence: 99%

Molecular Mechanisms of the Anti-Inflammatory Effects of Epigallocatechin 3-Gallate (EGCG) in LPS-Activated BV-2 Microglia Cells

et al. 2023

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Chronic neuroinflammation is associated with many neurodegenerative diseases, such as Alzheimer’s. Microglia are the brain’s primary immune cells, and when activated, they release various proinflammatory cytokines. Several natural compounds with anti-inflammatory and antioxidant properties, such as epigallocatechin 3-gallate (EGCG), may provide a promising strategy for inflammation-related neurodegenerative diseases involving activated microglia cells. The objective of the current study was to examine the molecular targets underlying the anti-inflammatory effects of EGCG in activated microglia cells. BV-2 microglia cells were grown, stimulated, and treated with EGCG. Cytotoxicity and nitric oxide (NO) production were evaluated. Immunoassay, PCR array, and WES™ Technology were utilized to evaluate inflammatory, neuroprotective modulators as well as signaling pathways involved in the mechanistic action of neuroinflammation. Our findings showed that EGCG significantly inhibited proinflammatory mediator NO production in LPS-stimulated BV-2 microglia cells. In addition, ELISA analysis revealed that EGCG significantly decreases the release of proinflammatory cytokine IL-6 while it increases the release of TNF-α. PCR array analysis showed that EGCG downregulated MIF, CCL-2, and CSF2. It also upregulated IL-3, IL-11, and TNFS10. Furthermore, the analysis of inflammatory signaling pathways showed that EGCG significantly downregulated mRNA expression of mTOR, NF-κB2, STAT1, Akt3, CCL5, and SMAD3 while significantly upregulating the expression of mRNA of Ins2, Pld2, A20/TNFAIP3, and GAB1. Additionally, EGCG reduced the relative protein expression of NF-κB2, mTOR, and Akt3. These findings suggest that EGCG may be used for its anti-inflammatory effects to prevent neurodegenerative diseases.

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