Perturbation of sphingolipid metabolism and ceramide production in HIV‐dementia

Haughey, Norman J.; Cutler, Roy G.; Tamara, Anita; McArthur, Justin C.; Vargas, Diana; Pardo, Carlos A.; Turchan, Jadwiga; Nath, Avindra; Mattson, Mark P.

doi:10.1002/ana.10828

Cited by 242 publications

(313 citation statements)

References 52 publications

Supporting

Mentioning

302

Contrasting

Unclassified

Order By: Relevance

“…There are at least five types of Smases, including the ubiquitous lysosomal acid SMase, the zinc-dependent secreted acid SMase, a neutral, Mg 2+ -dependent SMase, a neutral Mg 2+ -independent SMase, and an alkaline SMase. Neutral sphingomyelinase 2 (nSMase2) is a brain-specific nSMase that is thought to be located on the inner leaflet of the plasma membrane and is activated by phosphatidylserine and cellular stressors including the inflammatory cytokines TNFα, IL-1, Fas-L, UV irradiation, the neurotoxic HIV-proteins gp120 and Tat, and amyloid β (Brann et al 1999;Sortino et al 1999;Haughey et al 2003;Castiglione et al 2004;Lee et al 2004;Sanchez-Alavez et al 2006). Once nSMase2 is active, sphingomyelin shifts to the innerleaflet of the plasma membrane, where it can be catabolized to ceramide.…”

Section: Discussionmentioning

confidence: 99%

“…Total lipids from samples were prepared according to a modified Bligh and Dyer procedure (Haughey et al 2004). Briefly, each sample was homogenized at room temperature in 10 volumes of deionized water containing 300 nM EDTA, followed by 3 volumes of 100% methanol containing 53 mM ammonium formate and vortexed.…”

Section: Lipid Extraction Of Tissue and Cellsmentioning

confidence: 99%

“…ESI/MS/MS analyses were performed by methods similar to those used in previous studies (Cutler et al 2004b;Haughey et al 2004). Samples were injected using a Harvard Apparatus pump at 5 µl/min into an electrospray ionization (Turbo Ion Spray) Sciex API 3,000 triple stage quadrupole tandem mass spectrometer (ESIMS/MS) from Sciex Inc. (Thornhill, Ontario, Canada) operated in the positive mode.…”

Section: Measurement Of Sphingolipids Phospholipids Cholesterol Andmentioning

confidence: 99%

See 2 more Smart Citations

ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain

Bandaru

Troncoso

Wheeler

et al. 2009

Neurobiology of Aging

Self Cite

129

106

View full text Add to dashboard Cite

The ε4 allele of ApoE is associated with an earlier onset and faster progression of Alzheimer's disease in patients with the familial form of this neurodegenerative condition. Although ApoE4 has been repeatedly associated with altered sphingomyelin and cholesterol levels in tissue culture and rodent models, there has not been a direct quantification of sphingomyelin or sterol levels in the brains of patients with different forms of ApoE. We measured the sphingolipid and sterol content of human brain tissues and found no evidence of perturbed sterol or sphingolipid biochemistry in the brains of individuals expressing ApoE4 who did not have a preexisting neurodegenerative condition. Nevertheless, ApoE4 was associated with gross abnormalities in the sterol and sphingolipid content of numerous brain regions in patients with Alzheimer's diseease. The findings suggest that ApoE4 may not by itself alter sterol or sphingolipid metabolism in the brain under normal conditions, but that other neuropathologic changes of Alzheimer's are required to unmask the effect of ApoE4, and to perturb sterol and sphingolipid biochemistry.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Lipid Extraction Of Tissue and Cellsmentioning

confidence: 99%

Section: Measurement Of Sphingolipids Phospholipids Cholesterol Andmentioning

confidence: 99%

See 1 more Smart Citation

ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain

Bandaru

Troncoso

Wheeler

et al. 2009

Neurobiology of Aging

Self Cite

129

106

View full text Add to dashboard Cite

show abstract

“…Ceramide concentrations (ng mL −1 ) were determined by fitting the identified ceramide species to these standard curves based on acyl chain length. Instrument control and quantitation of spectral data were performed using Analyst 1.4.2 and MultiQuant software (AB Sciex Inc) (Haughey et al ., 2004; Bandaru et al ., 2013; Mielke et al ., 2015). …”

Section: Methodsmentioning

confidence: 99%

Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54–96 years from the Baltimore Longitudinal Study of Aging

Fabbri

Simonsick

et al. 2016

Aging Cell

Self Cite

View full text Add to dashboard Cite

SummaryCardiorespiratory fitness (VO 2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO 2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA). Individual species of ceramide were quantified by HPLC–tandem mass spectrometry. VO 2 peak was measured by a graded treadmill test. We applied multiple regression models to test the associations between ceramide species and VO 2 peak, while adjusting for age, sex, blood pressure, serum LDL, HDL, triglycerides, and other covariates. We found that higher levels of circulating C18:0, C20:0, C24:1 ceramides and C20:0 dihydroceramides were strongly associated with lower aerobic capacity (P < 0.001, P < 0.001, P = 0.018, and P < 0.001, respectively). The associations held true for both sexes (with men having a stronger association than women, P value for sex interaction <0.05) and were unchanged after adjusting for confounders and multiple comparison correction. Interestingly, no significant association was found for C16:0, C22:0, C24:0, C26:0, and C22:1 ceramide species, C24:0 dihydroceramide, or total ceramides. Our analysis reveals that specific long‐chain ceramides strongly associate with low cardiovascular fitness in older adults and may be implicated in the pathogenesis of low fitness with aging. Longitudinal studies are needed to further validate these associations and investigate the relationship between ceramides and health outcomes.

show abstract

“…Recientemente se reportaron niveles significativamente aumentados de productos metabólicos de los gangliósidos en el tejido cerebral y el LCR de individuos con demencia asociada con el VIH-1 (86). Existe, también, evidencia que sugiere la presencia de estados desmielinizantes en individuos infectados por el VIH-1; se ha reportado una asociación significativa entre los niveles elevados de la proteína mielínica básica (PMB) en el LCR y el desarrollo de demencia en individuos infectados (87).…”

Section: La Mielinización Un Evento Fundamental En El Desarrollo Delunclassified

El virus de la inmunodeficiencia humana tipo 1 y el sistema nervioso central en desarrollo.

et al. 2005

View full text Add to dashboard Cite

Actualmente, hay más de 42 millones de infectados con el virus de la inmunodeficiencia humana tipo 1 (VIH-1), de los cuales, 3,2 millones son niños y, de éstos, el 90% con transmisión vertical de la infección. Se considera que en Colombia más de 200.000 personas se han infectado desde el inicio de la pandemia y los estudios muestran una tendencia constante al aumento en las cifras de seroprevalencia en mujeres embarazadas y, por ende, en el número de recién nacidos infectados. El VIH-1 es primordialmente linfotrópico, pero su tropismo por el sistema nervioso central (SNC) es bien conocido, lo que genera múltiples alteraciones neurológicas, particularmente prominentes en niños, de las cuales la más prevalerte es la encefalopatía. Clásicamente, se reconocen dos tipos de encefalopatía en esta población: encefalopatía temprana y tardía, ambas con diferentes características clínicas e inmunológicas. La infección por el VIH-1 en el SNC está limitada a los macrófagos, la microglía y los astrocitos en menor escala. Las neuronas, células principalmente afectadas en los pacientes con sida, raras veces son infectadas, por lo que se postula que factores solubles, provenientes tanto del huésped como del virus, son los principales causantes del daño neuronal. Los hallazgos presentados en esta revisión sugieren la posibilidad de que el SNC, en etapas tempranas del desarrollo, sea especialmente susceptible a la infección por el VIH-1. Las cifras epidemiológicas sugieren que este tipo de alteraciones clínicas serán cada vez más frecuentes; de ahí, la importancia de conocer la neuropatogénesis de la infección por el VIH-1.Palabras clave: encefalitis, VIH-1, neuropatogénesis, neurogénesis, citocinas, embriología. The human immunodeficiency virus type 1 and the developing central nervous systemCurrently, at least 42 million people are infected worldwide with the human immunodeficiency virus type 1 (HIV-1). Of these, 3.2 million are children infected, in 90% of the cases, through vertical transmission. In Colombia, approximately 200,000 persons have been infected since the beginning of the pandemic, with an increasing trend in the seroprevalence among pregnant women. Although HIV-1 is basically lymphotropic, its capacity to invade the central nervous system (CNS) is well known, generating multiple neurological alterations, especially prominent in children, with encephalopathy being the most prevalent. Classically, two types of neurological disorders are recognized in children, consisting of early and late encephalopathies, each with differing clinical and immunological characteristics. HIV-1 infection of the CNS is limited to macrophages, microglia and astrocytes in a restricted manner. In patients with acquired immunodeficiency virus (AIDS), neurons are rarely infected, suggesting that cellular and viral soluble factors, are responsible for the neuronal damage. The conclusion is that the CNS in earlier stages of development is especially susceptible to HIV-1 infection. The epidemiological trends predict that these types of clinical...

show abstract

Perturbation of sphingolipid metabolism and ceramide production in HIV‐dementia

Cited by 242 publications

References 52 publications

ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain

ApoE4 disrupts sterol and sphingolipid metabolism in Alzheimer's but not normal brain

Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54–96 years from the Baltimore Longitudinal Study of Aging

El virus de la inmunodeficiencia humana tipo 1 y el sistema nervioso central en desarrollo.

Contact Info

Product

Resources

About