Rapid and persistent loss of TXNIP in HT22 neuronal cells under carbonyl and hyperosmotic stress
| Autor: | Ariana Ern Schmitz, Alcir Luiz Dafre, Pamela Maher |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Time Factors Thioredoxin-Interacting Protein Phenformin 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Mice 0302 clinical medicine Thioredoxins Osmotic Pressure Animals RNA Small Interfering PI3K/AKT/mTOR pathway Cell Line Transformed Neurons Chemistry Autophagy Glucose transporter AMPK Cell Biology Carbon Cell biology Oxidative Stress 030104 developmental biology Thioredoxin Carrier Proteins 030217 neurology & neurosurgery TXNIP |
| Zdroj: | Neurochemistry international. 132 |
| ISSN: | 1872-9754 |
| Popis: | Thioredoxin interacting protein (TXNIP) binds to thioredoxin thereby limiting its activity, but it also promotes internalization of glucose transporters, participates in inflammasome activation, and controls autophagy. Published data and this work demonstrate that TXNIP responds to a number of apparently unrelated stresses, such as serum deprivation, pH change, and oxidative, osmotic and carbonyl stress. Interestingly, we noticed that hyperosmotic (NaCl) and carbonyl (methylglyoxal, MGO) stresses in HT22 neuronal cells produced a rapid loss of TXNIP (half-life ∼12 min), prompting us to search for possible mechanisms controlling this TXNIP loss, including pH change, serum deprivation, calcium metabolism and inhibition of the proteasome and other proteases, autophagy and MAPKs. None of these routes stopped the TXNIP loss induced by hyperosmotic and carbonyl stress. Besides transcriptional, translational and microRNA regulation, there is evidence indicating that mTOR and AMPK also control TXNIP expression. Indeed, AMPK-deficient mouse embryonic fibroblasts failed to respond to phenformin (AMPK activator) and compound C (AMPK inhibitor), while rapamycin induced a marked increase in TXNIP levels, confirming the known AMPK/mTOR control over TXNIP. However, the TXNIP loss induced by NaCl or MGO were observed even in AMPK deficient MEFs or after mTOR inhibition, indicating AMPK/mTOR does not participate in this rapid TXNIP loss. These results suggest that rapid TXNIP loss is a general and immediate response to stress that can improve energy availability and antioxidant protection, eventually culminating in better cell survival. |
| Databáze: | OpenAIRE |
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