Effect of Tauroursodeoxycholic Acid and 4-Phenylbutyric Acid on Metabolism of Copper and Zinc in Type 1 Diabetic Mice Model

Zhou, Qi; Wang, Di; Xu, Jiancheng; Chi, Baorong

doi:10.1007/s12011-015-0474-5

Cited by 17 publications

(16 citation statements)

References 28 publications

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Section: Tudca In Diabetes and Obesitymentioning

confidence: 97%

“…Interestingly, the latest studies suggest a novel UPR-independent mechanism of TUDCA beneficial activity in type 1 diabetes, consisting of the regulation of micronutrients metabolism [117,118]. These studies imply an important role of Mg 2+ and Ca 2+ [118], as well as Cu 2+ and Zn 2+ [117] in glycemic control in type 1 diabetic mice models. It has been shown that levels of these microelements were altered significantly during the progress of diabetes, and long-term administration of TUDCA restored Mg 2+ , Ca 2+ , Cu 2+ , and Zn 2+ levels to normal values [117,118].…”

Section: Tudca In Diabetes and Obesitymentioning

confidence: 97%

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Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Kusaczuk

2019

Cells

153

125

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Tauroursodeoxycholic acid (TUDCA) is a naturally occurring hydrophilic bile acid that has been used for centuries in Chinese medicine. Chemically, TUDCA is a taurine conjugate of ursodeoxycholic acid (UDCA), which in contemporary pharmacology is approved by Food and Drug Administration (FDA) for treatment of primary biliary cholangitis. Interestingly, numerous recent studies demonstrate that mechanisms of TUDCA functioning extend beyond hepatobiliary disorders. Thus, TUDCA has been demonstrated to display potential therapeutic benefits in various models of many diseases such as diabetes, obesity, and neurodegenerative diseases, mostly due to its cytoprotective effect. The mechanisms underlying this cytoprotective activity have been mainly attributed to alleviation of endoplasmic reticulum (ER) stress and stabilization of the unfolded protein response (UPR), which contributed to naming TUDCA as a chemical chaperone. Apart from that, TUDCA has also been found to reduce oxidative stress, suppress apoptosis, and decrease inflammation in many in-vitro and in-vivo models of various diseases. The latest research suggests that TUDCA can also play a role as an epigenetic modulator and act as therapeutic agent in certain types of cancer. Nevertheless, despite the massive amount of evidence demonstrating positive effects of TUDCA in pre-clinical studies, there are certain limitations restraining its wide use in patients. Here, molecular and cellular modes of action of TUDCA are described and therapeutic opportunities and limitations of this bile acid are discussed.

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Section: Tudca In Diabetes and Obesitymentioning

confidence: 97%

Section: Tudca In Diabetes and Obesitymentioning

confidence: 97%

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Kusaczuk

2019

Cells

153

125

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“…For example, through specifically reduction in microglial reactivity, TUDCA can inhibit microglial migration in mice hippocampus [25] and prevent retinal degeneration [26]. TUDCA is also regarded as an inhibitor of ER stress, whose inhibition has been well-documented to mediate the protective effects of TUDCA on diabetes, obesity, and major depression [27][28][29]. Within these contexts, we hypothesize that TUDCA may have antidepressantlike activities, and attenuation of neuroinflammation, oxido-nitrosative stress, or ER stress may be a core mechanism for the antidepressant-like effect of TUDCA.…”

Section: Introductionmentioning

confidence: 99%

Tauroursodeoxycholic acid produces antidepressant‐like effects in a chronic unpredictable stress model of depression via attenuation of neuroinflammation, oxido‐nitrosative stress, and endoplasmic reticulum stress

Yang

Zhang

et al. 2018

Fundamemntal Clinical Pharma

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Depression is a common psychiatric disorder with heavy economic and social burdens. Searching new agents with better antidepressant-like activities is of great significance for depression therapy. Tauroursodeoxycholic acid (TUDCA), a clinical drug for gallstone treatment, possesses neuroprotective effects in different brain disorders. However, whether it affects depression remains unclear. We addressed this issue by evaluating the effect of TUDCA on depression induced by chronic unpredictable stress (CUS). Results showed that TUDCA treatment at 200 but not 100 mg/kg prevented the 5 weeks of CUS-induced increases in the immobile time of C57BL6/J mice in the experiments of forced swimming test and tail suspension test as well as the CUS-induced decrease in sucrose intake and crossing numbers in the open-field test, and did not enhance the antidepressant-like effect of fluoxetine. Attenuation of neuroinflammation may be involved in the antidepressant-like effect of TUDCA, as TUDCA treatment (200 mg/kg) normalized the levels of tumor necrosis factor-α and interleukin-6 in both hippocampus and prefrontal cortex. The increases in inflammasome and microglial activation markers, including interleukin-β, nod-like receptor protein 3, and Iba-1, in CUS-treated mice were reduced by TUDCA treatment (200 mg/kg). TUDCA treatment (200 mg/kg) also normalized the changes in markers reflecting the oxidative-nitrosative and endoplasmic reticulum (ER) stress induced by CUS, such as nitric oxide, reduced glutathione, malondialdehyde, glucose-regulated protein 78, and C/EBP homologous protein. These results revealed that TUDCA improved the CUS-induced depression-like behaviors likely through attenuation of neuroinflammation, oxido-nitrosative, and ER stress.

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“…TUDCA is approved by the U.S. Food and Drug Administration for use in biliary cirrhosis, and it is used effectively for cholestatic liver diseases11. Recent studies have revealed that TUDCA has an ameliorating effect on several diseases, including neurodegenerative diseases, osteoarthritis, vascular diseases, and diabetes12131415. In addition, TUDCA regulates stem cell differentiation into various lineages such as adipogenic and osteogenic lineages1617.…”

mentioning

confidence: 99%

Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein

Yoon

Lee

Yun

et al. 2016

Sci Rep

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Although mesenchymal stem cells (MSCs) are a promising cell source for regenerative medicine, ischemia-induced endoplasmic reticulum (ER) stress induces low MSC engraftment and limits their therapeutic efficacy. To overcome this, we investigated the protective effect of tauroursodeoxycholic acid (TUDCA), a bile acid, on ER stress in MSCs in vitro and in vivo. In ER stress conditions, TUDCA treatment of MSCs reduced the activation of ER stress-associated proteins, including GRP78, PERK, eIF2α, ATF4, IRE1α, JNK, p38, and CHOP. In particular, TUDCA inhibited the dissociation between GRP78 and PERK, resulting in reduced ER stress-mediated cell death. Next, to explore the ER stress protective mechanism induced by TUDCA treatment, TUDCA-mediated cellular prion protein (PrPC) activation was assessed. TUDCA treatment increased PrPC expression, which was regulated by Akt phosphorylation. Manganese-dependent superoxide dismutase (MnSOD) expression also increased significantly in response to signaling through the TUDCA-Akt axis. In a murine hindlimb ischemia model, TUDCA-treated MSC transplantation augmented the blood perfusion ratio, vessel formation, and transplanted cell survival more than untreated MSC transplantation did. Augmented functional recovery following MSC transplantation was blocked by PrPC downregulation. This study is the first to demonstrate that TUDCA protects MSCs against ER stress via Akt-dependent PrPC and Akt-MnSOD pathway.

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Effect of Tauroursodeoxycholic Acid and 4-Phenylbutyric Acid on Metabolism of Copper and Zinc in Type 1 Diabetic Mice Model

Cited by 17 publications

References 28 publications

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Tauroursodeoxycholate—Bile Acid with Chaperoning Activity: Molecular and Cellular Effects and Therapeutic Perspectives

Tauroursodeoxycholic acid produces antidepressant‐like effects in a chronic unpredictable stress model of depression via attenuation of neuroinflammation, oxido‐nitrosative stress, and endoplasmic reticulum stress

Tauroursodeoxycholic acid reduces ER stress by regulating of Akt-dependent cellular prion protein

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