Article ; Online: Arginine depletion attenuates renal cystogenesis in tuberous sclerosis complex model.
Cell reports. Medicine
2023 Volume 4, Issue 6, Page(s) 101073
Abstract: Cystic kidney disease is a leading cause of morbidity in patients with tuberous sclerosis complex (TSC). We characterize the misregulated metabolic pathways using cell lines, a TSC mouse model, and human kidney sections. Our study reveals a substantial ... ...
| Abstract | Cystic kidney disease is a leading cause of morbidity in patients with tuberous sclerosis complex (TSC). We characterize the misregulated metabolic pathways using cell lines, a TSC mouse model, and human kidney sections. Our study reveals a substantial perturbation in the arginine biosynthesis pathway in TSC models with overexpression of argininosuccinate synthetase 1 (ASS1). The rise in ASS1 expression is dependent on the mechanistic target of rapamycin complex 1 (mTORC1) activity. Arginine depletion prevents mTORC1 hyperactivation and cell cycle progression and averts cystogenic signaling overexpression of c-Myc and P65. Accordingly, an arginine-depleted diet substantially reduces the TSC cystic load in mice, indicating the potential therapeutic effects of arginine deprivation for the treatment of TSC-associated kidney disease. |
|---|---|
| MeSH term(s) | Humans ; Mice ; Animals ; Tuberous Sclerosis Complex 2 Protein/metabolism ; Tuberous Sclerosis/metabolism ; Arginine/metabolism ; Mechanistic Target of Rapamycin Complex 1 ; Kidney/metabolism |
| Chemical Substances | Tuberous Sclerosis Complex 2 Protein ; Arginine (94ZLA3W45F) ; Mechanistic Target of Rapamycin Complex 1 (EC 2.7.11.1) |
| Language | English |
| Publishing date | 2023-06-07 |
| Publishing country | United States |
| Document type | Journal Article ; Research Support, Non-U.S. Gov't |
| ISSN | 2666-3791 |
| ISSN (online) | 2666-3791 |
| DOI | 10.1016/j.xcrm.2023.101073 |
| Database | MEDical Literature Analysis and Retrieval System OnLINE |
More links
Kategorien
Order via subito
This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.
Inter-library loan at ZB MED
Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.