Cholesterol-derived bile acids enhance the chaperone activity of α-crystallins

Song, S.; Liang, Jinghang; Mulhern, Michael L.; Madson, Christian J.; Shinohara, Toshimichi

doi:10.1007/s12192-011-0259-5

Cited by 14 publications

(15 citation statements)

References 23 publications

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“…In the present study, UDCA treatment mediated modulation to altered tertiary structural changes in a noticeable way. These changes were previously observed and attributed to the power of UDCA to improve the chaperone function of lens crystallins with subsequent reduction of protein aggregations .…”

Section: Discussionsupporting

confidence: 63%

Ursodeoxycholic acid suppresses the formation of fructose/streptozotocin‐induced diabetic cataract in rats

Abdel-Ghaffar

Ghanem

Ahmed

et al. 2018

Fundamemntal Clinical Pharma

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The main objective of this study was to investigate the potential protective effect of ursodeoxycholic acid (UDCA) on fructose/streptozotocin-induced diabetic cataract in rats. The diabetic model (DM) was induced through the administration of 10% fructose in drinking water for 2 weeks followed by streptozotocin injection (intraperitoneal). One week later, hyperglycemia was assisted and diabetic animals were treated with UDCA either as local eye drops (0.5% solution, four times/day) or orally (100 mg/kg b.w.). Cataract formation was monitored biweekly and scored into four stages. After 12 weeks of treatment, rats were subjected to ophthalmological examination, and then, their blood and lenses were prepared for biochemical analysis of glucose, insulin, reduced glutathione, total antioxidant capacity, malondialdehyde, hydrogen peroxide, caspase-12, and lenticular total proteins. In addition, tertiary structure and conformational changes of lenticular soluble proteins were analyzed using SDS-PAGE and UV absorption while changes in lenticular α-crystallin structure were investigated using intrinsic tryptophan fluorescence. Results demonstrated that both local and oral UDCA restored the normal levels of lens T-AOC, MDA, H O , and caspase-12 and improved noticeably the levels of the lens GSH and total proteins. In addition, conformational and tertiary structure changes of soluble lens proteins were significantly reduced in UDCA-treated groups. Morphological examination of lenses revealed decreased score of cataract progression in UDCA-treated groups compared to DM animals. It was concluded that UDCA decreased the incidence of diabetic cataract by maintaining the antioxidant status, reducing the endoplasmic reticulum stress, and suppressing the structural changes of soluble lens proteins.

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Section: Discussionsupporting

confidence: 63%

Ursodeoxycholic acid suppresses the formation of fructose/streptozotocin‐induced diabetic cataract in rats

Abdel-Ghaffar

Ghanem

Ahmed

et al. 2018

Fundamemntal Clinical Pharma

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“…On the other hand, other authors have recently demonstrated that TUDCA per se or as a cochaperone of other complexes has a suppressive effect in the thermal aggregation of different proteins in vitro (Berger & Haller ; Song et al . ; Gani et al . ).…”

Section: Discussionmentioning

confidence: 99%

HOP3, a member of the HOP family in Arabidopsis, interacts with BiP and plays a major role in the ER stress response

Fernández-Bautista

Fernández‐Calvino

Muñoz

et al. 2017

Plant Cell & Environment

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HSP70-HSP90 organizing protein (HOP) is a well-studied family of cytosolic cochaperones. However, the possible role of HOP during the endoplasmic reticulum (ER) stress response and the identity of its interactors within the ER were not previously addressed in any eukaryote. We have demonstrated that Arabidopsis HOP3, whose function was not studied before, interacts in vivo with cytosolic HSP90 and HSP70, and, unexpectedly, with binding immunoglobulin protein (BiP), a HSP70 ER-resident protein. Although BiP lacks the domain described in other eukaryotes for HOP-HSP70 binding, it interacts with HOP3 through a non-canonical association to its nucleotide binding domain. Consistent with this interaction with BiP, HOP3 is partially localized at the ER. Moreover, HOP3 is induced both at transcript and protein levels by unfolded protein response (UPR) inducer agents by a mechanism dependent on inositol-requiring enzyme 1 (IRE1). Importantly, hop3 loss-of-function mutants show a reduction in pollen germination and a hypersensitive phenotype in the presence of ER stress inducer agents, a phenotype that is reverted by the addition of the chemical chaperone tauroursodeoxycholic acid (TUDCA). All these data demonstrate, for the first time in any eukaryote, a main role of HOP as an important regulator of the ER stress response, a process intimately linked in plants to important specific developmental programs and to environmental stress sensing and response.

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“…Studies of millimolar concentrations of TUDCA and UDCA have demonstrated their inhibitory effects on the thermal aggregation of different proteins. 52,53 This effect may have been secondary to the direct stabilization of the protein in question or through direct interaction with other molecular chaperones, enhancing their function. 52,54 However, this chaperone effect is not observed for all proteins; when neurodegenerative diseaserelated proteins like Aβ peptide were tested, TUDCA was found ineffective at preventing aggregation in vitro, 55 although these latter experiments were performed with lower concentrations of TUDCA (micromolar).…”

Section: Lipids and Detergents (Bile Acids)mentioning

confidence: 99%