Sterol profiles in plasma and erythrocyte membranes in patients with Smith-Lemli-Opitz syndrome: a six-year experience

Corso, Gaetano; Gelzo, Monica; Barone, Rosalba; Clericuzio, Stefano; Pianese, Pierluigi; Nappi, Angela; Russo, Antonio Dello

doi:10.1515/cclm.2011.689

Cited by 17 publications

(16 citation statements)

References 26 publications

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“…Results of the RBC sterol composition analysis are comparable to the comprehensive study by Russo et al [16].…”

Section: Sterol Composition Of Slos Membranesupporting

confidence: 84%

“…The laboratory medicine profile (i.e., serum sterols) of SLOS patients is quite diverse, a wide range of plasma 7DHC and CHOL concentrations were reported even for genetically homogenous patient groups [16,42]. Furthermore, the 7DHC/CHOL ratios in the plasma and in red blood cells also show significant variations among patients.…”

Section: Discussionmentioning

confidence: 99%

“…We characterized the sterol profile of the red blood cells (RBCs) from SLOS patients and age-matched control donors in order to gain information regarding the alteration of the sterol environment, and especially that of the 7DHC/CHOL ratio in the cell membrane induced by the SLOS disease [16,61]. Table 1 shows the elevated 7DHC and reduced CHOL levels in all of the SLOS samples, while 7DHC in the control samples was undetectable.…”

Section: Sterol Composition Of Slos Membranementioning

confidence: 99%

“…Irons and his colleagues showed that the SLOS is caused by the deficiency of 7-dehyrocholesterol-reductase (DHCR7), which catalyzes the last step in the CHOL biosynthetic pathway [29]. Altered DHCR7 activity led to increased 7DHC and reduced CHOL levels both in the serum and in the plasma membrane of fibroblasts and erythrocytes [16,61].The severity of the disease and life expectancy of the patients is mostly determined by initial serum CHOL level, while the ratio of 7DHC/CHOL has an additional prognostic value [5]. Oral cholesterol and simvastatin administration are used in the treatment of SLOS; however, retrospective studies did not confirm its effectiveness [12,19,24,58].…”

Section: Introductionmentioning

confidence: 99%

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7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

Balajthy

Somodi

Pethő

et al. 2016

Pflugers Arch - Eur J Physiol

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In vitro manipulation of membrane sterol level affects the regulation of ion channels and consequently certain cellular functions; however, a comprehensive study that confirms the pathophysiological significance of these results is missing. The malfunction of 7-dehydrocholesterol (7DHC) reductase in Smith-Lemli-Opitz syndrome (SLOS) leads to the elevation of the 7-dehydrocholesterol level in the plasma membrane. T lymphocytes were isolated from SLOS patients to assess the effect of the in vivo altered membrane sterol composition on the operation of the voltage-gated Kv1.3 channel and the ion channel-dependent mitogenic responses. We found that the kinetic and equilibrium parameters of Kv1.3 activation changed in SLOS cells. Identical changes in Kv1.3 operation were observed when control/healthy T cells were loaded with 7DHC. Removal of the putative sterol binding sites on Kv1.3 resulted in a phenotype that was not influenced by the elevation in membrane sterol level. Functional assays exhibited impaired activation and proliferation rate of T cells probably partially due to the modified Kv1.3 operation. We concluded that the altered membrane sterol composition hindered the operation of Kv1.3 as well as the ion channel-controlled T cell functions.

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“…Results of the RBC sterol composition analysis are comparable to the comprehensive study by Russo et al [16].…”

Section: Sterol Composition Of Slos Membranesupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Section: Sterol Composition Of Slos Membranementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

Balajthy

Somodi

Pethő

et al. 2016

Pflugers Arch - Eur J Physiol

View full text Add to dashboard Cite

show abstract

“…MS analyses of SLOS and SLOS animal models have focused on analysis of sterols [72][73][74][75][76] but not on proteomic analyses. Proteomic identification of other components of cholesterol metabolism, such as apolipoproteins could be of value for understanding the consequences of this disorder and for identifying unique therapeutic targets.…”

Section: Smith Lemli Opitz Syndromementioning

confidence: 99%

The Potential for Proteomics in Understanding Neurodevelopmental Disorders

Wormwood¹,

Sokolowska

Ryan

et al. 2015

J Proteomics Bioinform

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Sterol and steroid catabolites from cholesterol produced by the psychrophile Pseudoalteromonas haloplanktis

et al. 2014

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Pseudoalteromonas haloplanktis, a psychrotrophilic marine bacterium of biotechnological interest, shows anti-biofilm properties and is particularly relevant for cold storage of vacuum packed seafood. We focused our interest on the activation of cholesterol metabolism in this bacterium as the presence in its genome of a putative 3-ketosteroid-Δ(1) -dehydrogenase. This study reports GC-MS and LC-MS/MS profiles of sterols/steroids and their derivatives found in cell extracts of P. haloplanktis grown in a medium with a low content of cholesterol. Here, for the first time, we suggest that P. haloplanktis produces some intermediates of cholesterol catabolism, putatively identified as 24-hydroxycholest-1,4-dien-3-one-26-oic acid, chol-1,4-dien-3-one-24-oic acid, 26-hydroxycholest-4-en-3-one, and pregn-4-en-3-one-20-carboxylic acid, a finding already reported in other microorganisms. The presence of these compounds, also considered steroid precursors, produced by P. haloplanktis in vacuum packed seafood could be of interest for healthy of consumers, as well as, for biotechnological applications in pharmaceutical industry.

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Sterol profiles in plasma and erythrocyte membranes in patients with Smith-Lemli-Opitz syndrome: a six-year experience

Abstract: The results of this study may be helpful for diagnosis and interpretation of data in patients with findings suggestive of a cholesterol biosynthesis defect.

Cited by 17 publications

References 26 publications

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

7DHC-induced changes of Kv1.3 operation contributes to modified T cell function in Smith-Lemli-Opitz syndrome

The Potential for Proteomics in Understanding Neurodevelopmental Disorders

Sterol and steroid catabolites from cholesterol produced by the psychrophile Pseudoalteromonas haloplanktis

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