Hyaluronic acid regulates a key redox control factor Nrf2 via phosphorylation of Akt in bovine articular chondrocytes
| Autor: | Toshiyuki Takehara, Kanji Fukuda, Takeshi Teramura, Yuta Onodera |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Small interfering RNA
QH301-705.5 Hyaluronic acid digestive system environment and public health General Biochemistry Genetics and Molecular Biology Article Extracellular matrix chemistry.chemical_compound ROS reactive oxygen species Chondrocytes Downregulation and upregulation Nrf2 nuclear factor-erythroid-2-related factor 2 Biology (General) Receptor Transcription factor Protein kinase B HA hyaluronic acid Chemistry Reactive oxygen species (ROS) respiratory system Cell biology Immunology Phosphorylation Nuclear factor-erythroid-2-related factor 2 (Nrf2) |
| Zdroj: | FEBS Open Bio FEBS Open Bio, Vol 5, Iss 1, Pp 476-484 (2015) |
| ISSN: | 2211-5463 |
| Popis: | Highlights • Hyaluronic acid (HA) has a pharmacological role for reduction of cellular superoxide. • In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated. • Inhibition of Akt or suppression of HA receptors prevented HA-mediated Nrf2 accumulation. • Nrf2 siRNA inhibited the HA effect on antioxidant enzymes. • HA might contribute to ROS reduction through Nrf2 regulation by activating Akt. One important pharmacological function of hyaluronic acid (HA) in chondrocytes is reduction of cellular superoxide generation and accumulation. Here we demonstrated a relationship between HA supplementation and accumulation of Nuclear factor-erythroid-2-related factor 2 (Nrf2), which is a master transcription factor in cellular redox reactions, in cultured chondrocytes derived from bovine joint cartilage. In HA-treated chondrocytes, expression of Nrf2 and its downstream genes was upregulated. In HA-treated chondrocytes, Akt was phosphorylated, and inhibition of Akt activity or suppression of HA receptors CD44 and/or RHAMM with siRNAs prevented HA-mediated Nrf2 accumulation. Furthermore, Nrf2 siRNA inhibited the HA effect on antioxidant enzymes. These results show that HA might contribute to ROS reduction through Nrf2 regulation by activating Akt. Our study suggests a new mechanism for extracellular matrix (ECM)-mediated redox systems in chondrocytes. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Plný text