Samar M Hammad, Jean-Philip Truman, Mohammed M Al Gadban, Kent J Smith, Waleed O Twal, Mark B Hamner
{"title":"ALTERED BLOOD SPHINGOLIPIDOMICS AND ELEVATED PLASMA INFLAMMATORY CYTOKINES IN COMBAT VETERANS WITH POST-TRAUMATIC STRESS DISORDER.","authors":"Samar M Hammad, Jean-Philip Truman, Mohammed M Al Gadban, Kent J Smith, Waleed O Twal, Mark B Hamner","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Patients with post-traumatic stress disorder (PTSD) have greater risk of developing cardiovascular disease (CVD). While chronically elevated plasma cholesterol and pro-inflammatory cytokines levels increase CVD risk, several studies have shown that cholesterol reduction does not reduce CVD risk. Acid sphingomyelinase (ASMase) activation has been implicated in both CVD and major depressive disorder. We investigated plasma pro-inflammatory cytokine levels, ASMase activity, and changes in sphingolipids in PTSD patients compared to healthy controls. Levels of interleukin 6, interleukin 10, interferon-γ and tumor necrosis factor-α were higher in PTSD patients than controls. Plasma ASMase activity and sphingosine 1-phosphate were higher in the PTSD group (1.6-fold and 2-fold, respectively; <i>p</i><0.05). The results suggest that CVD risk factors in PTSD patients remain high despite cholesterol reduction.</p>","PeriodicalId":88942,"journal":{"name":"Neurobiology of lipids","volume":"10 ","pages":"2"},"PeriodicalIF":0.0,"publicationDate":"2012-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3882130/pdf/nihms-396186.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32011960","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"PARADOXICAL RESPONSES TO NEUROTOXIC STERYL GLYCOSIDES: INSIGHTS FROM A CELLULAR MODEL OF ALSPDC.","authors":"Christopher A Shaw, Steven Pelech, Philip T T Ly","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The causes of many sporadic neurodegenerative diseases remain unknown making prevention difficult, if not impossible. One clue comes from the study of amyotrophic lateral sclerosis-parkinsonism dementia complex (ALS-PDC) of Guam which shares many similarities with amyotrophic lateral sclerosis, Parkinson's disease, and Alzheimer's disease seen in other parts of the world. This disorder may provide a unique opportunity to study the cause and progression of neurodegenerative diseases. Epidemiological and experimental findings indicate that dietary consumption of cycad seeds is an underlying cause of ALS-PDC. Our laboratory provided evidence that a family of compounds called steryl glycosides are the active ingredients that may be responsible for producing the neurodegenerative outcome in ALS-PDC. Here, we review some of our work on the chronic toxicity of steryl glycosides in neuronal cells maintained in cell culture and in an in vivo mouse model. The current studies indicate some mechanisms about how neuronal cells respond to this class of toxins.</p>","PeriodicalId":88942,"journal":{"name":"Neurobiology of lipids","volume":"8 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2009-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3160139/pdf/nihms-171745.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"30101921","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cholesteryl Glucoside Stimulates Activation of Protein Kinase B/Akt in the Motor Neuron-Derived NSC34 Cell Line.","authors":"Philip T T Ly, Steven Pelech, Christopher A Shaw","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Steryl glycosides and related compounds are commonly found in the environment and have been associated with neurodegenerative changes in vulnerable individuals. However, their mechanisms of action in mammalian cells have not been well investigated. In the present study the effects of cholesterol glucoside (CG), a variant form of steryl glycoside, was investigated in the motor neuron-derived NSC34 cell line. Prolonged treatment with CG was found to induce cell death in a dose- and time-dependent manner. However, transient exposure of CG preconditioned NSC34 cells for stress from serum deprivation. To study the signaling pathways activated by CG, we employed the Kinetworks™ KPSS 1.3 Phospho-site Screen to track the phosphorylation level of at least 35 diverse signaling proteins. The survival protein kinase B (PKB/Akt) displayed a 2-fold increase in phosphorylation at its Ser-473 activation site following CG stimulation. Akt signaling was important for conferring cytoprotection against serum deprivation-induced stress. Inhibition of phosphatidylinositol 3-kinase (PI3K), which indirectly triggers Akt stimulation, completely abolished CG preconditioning against serum deprivation. Our findings revealed that there may be a PI3K-independent pathway which also mediated Akt Ser-473 phosphorylation. Improved understanding of the mechanisms of action of CG should provide insights to the how other members of the steryl glycoside family induce toxicity in the mouse model of ALS-PDC, and how cells respond to these toxins.</p>","PeriodicalId":88942,"journal":{"name":"Neurobiology of lipids","volume":"7 4","pages":"620081"},"PeriodicalIF":0.0,"publicationDate":"2008-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2950709/pdf/nihms83448.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"29345741","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}