Conformational Characterization of Ceramides by Nuclear Magnetic Resonance Spectroscopy

Li, Li; Tang, Xiaoping; Taylor, K. Grant; DuPré, Donald B.; Yappert, Marta C.

doi:10.1016/s0006-3495(02)75554-9

Cited by 65 publications

(85 citation statements)

References 75 publications

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“…1 H And 13 C NMR characteristics given in this paper agreed well with similar values found in chemical literature for ß-D-galactofuranosic ring [21,22,[27][28][29][30][31][32] as well as of aglycone [33,34].…”

Section: Discussionsupporting

confidence: 89%

Galactofuranosylated Galactocerebrosides, a New Drug Delivery System for Ceramides to Colon

Iga¹,

Iga²

2008

TOOCJ

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Section: Discussionsupporting

confidence: 89%

Galactofuranosylated Galactocerebrosides, a New Drug Delivery System for Ceramides to Colon

Iga¹,

Iga²

2008

TOOCJ

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“…The relationship between increased dihydroceramide levels and barrier dysfunction is also unclear. In contrast to what was observed in ceramides, the lack of the trans-double bond at position 4 in dihydroceramides causes a conformational distortion that might reduce hydrogen-bonding interaction with water molecules around their head groups (37). This could result in a reduction in the tightness of the packing of lipids in SC lamellar structures and affects skin permeability.…”

Section: Discussionmentioning

confidence: 82%

Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function

Takagi¹,

Tojo²,

Tomita³

et al. 2003

J. Clin. Invest.

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Aryl hydrocarbon receptor nuclear translocator (ARNT), a transcription factor of the Per/AHR/ ARNT/Sim family, regulates gene expression in response to environmental stimuli including xenobiotics and hypoxia. To examine its role in the epidermis, the Cre-loxP system was used to disrupt the Arnt gene in a keratinocyte-specific manner. Gene-targeted, newborn mice with almost normal appearance died neonatally of severe dehydration caused by water loss. Histology showed small changes in the architecture of cornified layers, with apparently preserved intercorneocyte lamellar structures responsible for the skin barrier function. In contrast, HPLC/ion-trap mass spectrometry revealed significant alterations in the compositions of ceramides, the major components of the lamellae. The murine epidermal ceramides normally contain 4-sphingenine and 4-hydroxysphinganine. In Arnt-null epidermis, 4-sphingenine was largely replaced by sphinganine and the amounts of ceramides with 4-hydroxysphinganine were greatly decreased, suggesting deficiency of dihydroceramide desaturases that catalyze the formation of both 4-sphingenyl and 4-hydroxysphinganyl moieties. A desaturase isoenzyme, DES-1, prefers desaturation, but DES-2 catalyzes both reactions to a similar extent. Transcript levels of Des-2, but not Des-1, were considerably decreased in cultured keratinocytes from Arntnull epidermis. These results indicate that proper ceramide compositions through 4-desaturation regulated by ARNT are crucial for maintaining the epidermal barrier function. .jp. Conflict of interest:The authors have declared that no conflict of interest exists. Nonstandard abbreviations used: aryl hydrocarbon receptor nuclear translocator (ARNT); basic helix-loop-helix (bHLH); aryl hydrocarbon receptor (AHR); Per/AHR/ARNT/Sim (PAS); hypoxia-inducible factor 1α (HIF1α); stratum corneum (SC); high-performance TLC (HPTLC); tandem mass spectrometry (MS/MS); embryonic day (E); electrospray ionization (ESI).

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“…Molecular dynamic simulations indicate that the presence of the double bond stabilizes ceramide channels via adjacent double bond-double bond interactions (Anishkin et al, 2006). An alternative hypothesis that could explain the importance of the double bond for channel formation is that the trans double bond in ceramide augments intramolecular hydration/hydrogen bonding in the polar region (Li et al, 2002;Brockman et al, 2004).…”

Section: Only a Small Percentage Of The Ceramide Added To Solution Inmentioning

confidence: 99%

Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations

2006

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Recent evidence suggests that the ability of ceramides to induce apoptosis is due to a direct action on mitochondria. Mitochondria are known to contain enzymes responsible for ceramide synthesis and hydrolysis and mitochondrial ceramide levels have been shown to be elevated prior to the mitochondrial phase of apoptosis. Ceramides have been reported to induce the release of intermembrane space proteins from mitochondria, which has been linked to their ability to form large channels in membranes. The aim of this study was to determine if the membrane concentration of ceramide required for the formation of protein permeable channels is within the range that is present in mitochondria during the induction phase of apoptosis. Only a very small percentage of the ceramide actually inserts into the mitochondrial membranes. The permeability of the mitochondrial outer membrane correlates directly with the level of ceramide in the membrane. Importantly, the concentration of ceramide at which significant channel formation occurs is consistent with the level of mitochondrial ceramide that occurs during the induction phase of apoptosis (4 pmol ceramide/ nanomole phospholipid). Similar results were obtained with short-and long-chain ceramide. Ceramide channel formation is specific to mitochondrial membranes in that no channel formation occurs in the plasma membranes of erythrocytes even at concentrations 20 times higher than those required for channel formation in mitochondrial outer membranes. Thus, ceramide channels are good candidates for the pathway by which proapoptotic proteins are released from mitochondria during the induction phase of apoptosis.

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Conformational Characterization of Ceramides by Nuclear Magnetic Resonance Spectroscopy

Cited by 65 publications

References 75 publications

Galactofuranosylated Galactocerebrosides, a New Drug Delivery System for Ceramides to Colon

Galactofuranosylated Galactocerebrosides, a New Drug Delivery System for Ceramides to Colon

Alteration of the 4-sphingenine scaffolds of ceramides in keratinocyte-specific Arnt-deficient mice affects skin barrier function

Ceramide forms channels in mitochondrial outer membranes at physiologically relevant concentrations

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