Tauroursodeoxycholic Acid Protects Against Mitochondrial Dysfunction and Cell Death via Mitophagy in Human Neuroblastoma Cells

Abstract

Mitochondrial dysfunction has been deeply implicated in the pathogenesis of several neurodegenerative diseases. Thus, to keep a healthy mitochondrial population, a balanced mitochondrial turnover must be achieved. Tauroursodeoxycholic acid (TUDCA) is neuroprotective in various neurodegenerative disease models; however, the mechanisms involved are still incompletely characterized. In this study, we investigated the neuroprotective role of TUDCA against mitochondrial damage triggered by the mitochondrial uncoupler carbonyl cyanide m-chlorophelyhydrazone (CCCP). Herein, we show that TUDCA significantly prevents CCCP-induced cell death, ROS generation, and mitochondrial damage. Our results indicate that the neuroprotective role of TUDCA in this cell model is mediated by parkin and depends on mitophagy. The demonstration that pharmacological up-regulation of mitophagy by TUDCA prevents neurodegeneration provides new insights for the use of TUDCA as a modulator of mitochondrial activity and turnover, with implications in neurodegenerative diseases.

Optimizing treatment of tauroursodeoxycholic acid to improve embryonic development after in vitro maturation of cumulus-free oocytes in mice

“…Currently, it is not clear why such a higher concentration of TUDCA is required to observe an effect in embryos. One possibility is that IVM oocytes may cause more ER stress or additional impairment to the mitochondria after IVF, as TUDCA treatment also protects against mitochondrial dysfunction [ 19 ]. Thus, the concentration of TUDCA used for treatment of IVM oocytes should be optimized differently from in vivo matured oocytes.…”

Translational approaches to restoring mitochondrial function in Parkinson's disease

“…Furthermore, several markers of apoptosis were attenuated including caspase 3 activation and nuclear fragmentation. Other, subsequent studies using TUDCA, the taurine conjugate of UDCA have shown very similar effects in the SHSY5Y model after CCCP treatment ; MMP and ROS were again normalised after TUDCA treatment. Mitochondrial dysfunction has been noted as a major phenotype in several Caenorhabditis elegans genetic models of PD induced by expressing or deleting alpha‐synuclein , parkin or DJ1 .…”

Tauroursodeoxycholic Acid (TUDCA)—Lipid Interactions and Antioxidant Properties of TUDCA Studied in Model of Photoreceptor Membranes

“…The therapeutic effect resulted in preservation of function and morphology of photoreceptor cells in retina [ 9 , 14 , 15 , 16 , 17 ]. Among the proposed mechanism of cytoprotective action of TUDCA we may include the inhibition of classic apoptosis pathways [ 18 ], decrease of endoplasmic reticulum stress and protein aggregation [ 19 , 20 ], stabilization of mitochondrial membranes [ 21 , 22 ], prevention of DNA damage [ 23 ], and stimulation of antioxidant mechanisms through activation of the nrf2 transcription factor [ 24 , 25 ]. The most recent data demonstrated that if ARPE–19 cells were exposed to H 2 O 2 in the presence of TUDCA, the bile acid increased cells viability and enhanced their antioxidant capacity by increasing the level of glutathione and upregulating the expression of antioxidant genes [ 25 ].…”