Interaction of GABA-mimetics with the taurine transporter (TauT, Slc6a6) in hyperosmotic treated Caco-2, LLC-PK1 and rat renal SKPT cells

Rasmussen, Rune; Lagunas, Candela; Plum, Jakob; Holm, René; Nielsen, Carsten Uhd

doi:10.1016/j.ejps.2015.11.020

Cited by 21 publications

(16 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, how are A1T levels modulated in response to shifts in taurine availability such as could occur due to inhibition of taurine transport? Interest in taurine has been intensified by reports that photoreceptor cell degeneration occurring as a side-effect of the antiepileptic drug vigabatrin (GABA-transaminase inhibitor) is due to taurine depletion (52,69,70). One might wonder whether the handling of retinaldehyde by taurine is involved in this toxicity.…”

Section: Discussionmentioning

confidence: 99%

Vitamin A aldehyde-taurine adduct and the visual cycle

Kim

Sparrow

2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Visual pigment consists of opsin covalently linked to the vitamin A-derived chromophore, 11-cis-retinaldehyde. Photon absorption causes the chromophore to isomerize from the 11-cis- to all-trans-retinal configuration. Continued light sensitivity necessitates the regeneration of 11-cis-retinal via a series of enzyme-catalyzed steps within the visual cycle. During this process, vitamin A aldehyde is shepherded within photoreceptors and retinal pigment epithelial cells to facilitate retinoid trafficking, to prevent nonspecific reactivity, and to conserve the 11-cis configuration. Here we show that redundancy in this system is provided by a protonated Schiff base adduct of retinaldehyde and taurine (A1-taurine, A1T) that forms reversibly by nonenzymatic reaction. A1T was present as 9-cis, 11-cis, 13-cis, and all-trans isomers, and the total levels were higher in neural retina than in retinal pigment epithelium (RPE). A1T was also more abundant under conditions in which 11-cis-retinaldehyde was higher; this included black versus albino mice, dark-adapted versus light-adapted mice, and mice carrying the Rpe65-Leu450 versus Rpe65-450Met variant. Taurine levels paralleled these differences in A1T. Moreover, A1T was substantially reduced in mice deficient in the Rpe65 isomerase and in mice deficient in cellular retinaldehyde-binding protein; in these models the production of 11-cis-retinal is compromised. A1T is an amphiphilic small molecule that may represent a mechanism for escorting retinaldehyde. The transient Schiff base conjugate that the primary amine of taurine forms with retinaldehyde would readily hydrolyze to release the retinoid and thus may embody a pool of 11-cis-retinal that can be marshalled in photoreceptor cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Vitamin A aldehyde-taurine adduct and the visual cycle

Kim

Sparrow

2020

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…68 b-alanine is also transported by the taurine/b-alanine transporter, Slc6a6. 69 Slc6a6 is widely expressed throughout the body and in the brain, 70,71 including in both neurons and glial cells. 72 In our previous RNA sequencing study of the medial prefrontal cortex that compared C57BL/6J mice under spontaneous sleep and sleep deprivation, expression of Slc6a6 was highly downregulated in sleep-deprived animals and upregulated in animals allowed to sleep.…”

Section: Discussionmentioning

confidence: 99%

The dihydropyrimidine dehydrogenase gene contributes to heritable differences in sleep in mice

Keenan¹,

Galante²,

Zhang³

et al. 2021

Current Biology

View full text Add to dashboard Cite

show abstract

“…Oral taurine supplementation (100 mg/kg/day, 2 years) enabled normal blood taurine levels, correction of the cardiomyopathy and non-progression of retinopathy in a 6-year-old [ 12 ]. Interest in taurine also originates from reports that the bilateral concentric visual field loss that is a side-effect of the anti-epileptic drug vigabatrin (GABA-transaminase inhibitor) is due to taurine depletion [ 2 , 13 , 14 ]. The photoreceptor cell degeneration occurring as a side-effect of vigabatrin is intensified by light exposure and albino mice are predisposed [ 15 ].…”

Section: Introductionmentioning

confidence: 99%