Tim Ashlin

GlaxoSmithKline | GSK

Phosphatidylinositol is the parent lipid for the synthesis of seven phosphorylated inositol lipids and each of them play specific roles in numerous processes including receptor-mediated signalling, actin cytoskeleton dynamics and membrane trafficking. PI synthesis is localised to the endoplasmic reticulum (ER) whilst its phosphorylated derivatives...

Chronic stimulation (24 h) with vasopressin leads to hypertrophy in H9c2 cardiomyoblasts and this is accompanied by continuous activation of phospholipase C. Consequently, vasopressin stimulation leads to a depletion of phosphatidylinositol levels. The substrate for phospholipase C is phosphatidylinositol (4, 5) bisphosphate (PIP 2 ) and resynthesi...

The lipid transporters of the phosphatidylinositol transfer protein (PITP) family dictate phosphoinositide compartmentalization, and specific phosphoinositides play crucial roles in signaling cascades, membrane traffic, ion channel regulation, and actin dynamics. Although PITPs are enriched in the brain, their physiological functions in neuronal si...

Document S1. Supplemental Experimental Procedures, Figures S1–S4, and Tables S1–S3

CDP diacylglycerol synthase (CDS) catalyses the conversion of phosphatidic acid (PA) to CDP-diacylglycerol, an essential intermediate in the synthesis of phosphatidylglycerol, cardiolipin and phosphatidylinositol (PI). CDS activity has been identified in mitochondria and endoplasmic reticulum of mammalian cells apparently encoded by two highly-rela...

Introduction Phosphatidylinositol transfer proteins (PITPs) regulate phosphoinositide metabolism and play diverse roles in multicellular organisms, from cancer regulation to sensory neuron signal transduction. One class II PITP family member, Piptnc1, has been implicated in cancer metastasis yet is also expressed in the developing and adult vertebr...

The anti-atherogenic cytokine TGF-β inhibits macrophage foam cell formation by suppressing the expression of key genes implicated in the uptake of modified lipoproteins. We have previously shown a critical role for p38 MAPK and JNK in the TGF-β-mediated regulation of apolipoprotein E expression in human monocytes. However, the roles of these two MA...

Pdr16p is considered a factor of clinical azole resistance in fungal pathogens. The most distinct phenotype of yeast cells lacking Pdr16p is their increased susceptibility to azole antifungals. Pdr16p (also known as Sfh3p) of Saccharomyces cerevisiae belongs to the Sec14 family of phosphatidylinositol transfer proteins. It facilitates transfer of p...

Atherosclerosis is an inflammatory disorder of the vasculature regulated by cytokines. Amongst the cytokines, IL-33 attenuates the development of atherosclerosis in mouse model systems via several mechanisms, including inhibition of macrophage foam cell formation and promotion of a Th1 to Th2 shift. Proteases produced by macrophages, such as matrix...

Atherosclerosis is an inflammatory disease of the vasculature regulated by cytokines. Macrophages play a crucial role at all stages of this disease, including regulation of foam cell formation, the inflammatory response and stability of atherosclerotic plaques. For example, matrix metalloproteinases produced by macrophages play an important role in...

A key event during the formation of lipid-rich foam cells during the progression of atherosclerosis is the uptake of modified low-density lipoproteins (LDL) by macrophages in response to atherogenic mediators in the arterial intima. In addition to scavenger receptor-dependent uptake of LDL, macropinocytosis is known to facilitate the uptake of LDL...

Liver X receptors (LXRs) belong to the nuclear receptor superfamily of ligand-dependent transcription factors. LXRs are activated by oxysterols, metabolites of cholesterol, and therefore act as intracellular sensors of this lipid. There are two LXR genes (α and β) that display distinct tissue/cell expression profiles. LXRs interact with regulatory...

Cardiovascular disease results in more deaths globally than any other ailment. A major contributing factor to its pathology is atherosclerosis; an inflammatory disorder characterized by the development of fibrotic plaques within the arterial walls. Key to the progression of atherosclerosis are macrophages that contribute to plaque development by tr...

Cardiovascular disease is the biggest killer globally and the principal contributing factor to the pathology is atherosclerosis; a chronic, inflammatory disorder characterized by lipid and cholesterol accumulation and the development of fibrotic plaques within the walls of large and medium arteries. Macrophages are fundamental to the immune respons...

Atherosclerosis is an inflammatory disorder of the vasculature that is orchestrated by the action of cytokines. Macrophages play a prominent role in all stages of this disease, including foam cell formation, production of reactive oxygen species, modulation of the inflammatory response and the regulation of the stability of atherosclerotic plaques....

The ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteases are secreted enzymes that regulate extracellular matrix turnover by degrading specific matrix components. Roles for the proteases in inflammation and atherosclerosis have been suggested by a number of recent studies, and the role of ADAMTS-4 and -5 in the breakdow...

The development of atherosclerosis, a chronic inflammatory disease characterized by the formation of arterial fibrotic plaques, has been shown to be reduced by IL-33 in vivo. However, whether IL-33 can directly affect macrophage foam cell formation, a key feature of atherosclerotic plaques, has not been determined. In this study, we investigated wh...