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At least 1,009 records · Page 56Linked to original sources
PubMed2005

CLA isomers inhibit TNFalpha-induced eicosanoid release from human vascular smooth muscle cells via a PPARgamma ligand-like action.

Conjugated linoleic acids (CLAs) were reported to have anti-atherogenic properties in animal feeding experiments. In an attempt to elucidate the molecular mechanisms of these anti-atherogenic effects, the modulatory potential of CLA on cytokine-induced eicosanoid production from smooth muscle cells (SMCs), which contributes to the chronic inflammatory response associated with atherosclerosis, has been investigated in the present study. cis-9, trans-11 CLA and trans-10, cis-12 CLA were shown to reduce proportions of the eicosanoid precursor arachidonic acid in SMC total lipids and to inhibit cytokine-induced NF-kappaB DNA-binding activity, mRNA levels of inducible enzymes involved in eicosanoid formation (cPLA2, COX-2, mPGES), and the production of the prostaglandins PGE2 and PGI2 by TNFalpha-stimulated SMCs in a dose-dependent manner. The effect of 50 micromol/L of either CLA isomer was as effective as 10 micromol/L of the PPARgamma agonist troglitazone in terms of inhibiting the TNFalpha-stimulated eicosanoid production by SMCs. PPARgamma DNA-binding activity was increased by both CLA isomers compared to control cells. Moreover, it was shown that the PPARgamma antagonist T0070907 partially abrogated the inhibitory action of CLA isomers on cytokine-induced eicosanoid production and NF-kappaB DNA-binding activity by vascular SMCs suggesting that PPARgamma signalling is at least partially involved in the action of CLA in human vascular SMCs. With respect to the effects of CLA on experimental atherosclerosis, our findings suggest that the anti-inflammatory effect of CLA is at least partially responsible for the anti-atherogenic effects of CLA observed in vivo.

Adult↗
PubMed2004

Expression and function of PPARgamma in rat placental development.

Peroxisome proliferator-activated receptor (PPAR) gamma is a nuclear receptor known to regulate adipogenesis. Deletion of the PPARgamma gene in the mouse results in death by embryonic day 10.0 (E10.0) due to the failure of establishment of a labyrinth layer in the placenta, which suggests that PPARgamma is involved in trophoblast differentiation. To define PPARgamma function further in placental development, the expression and localization of the PPARgamma gene in the rat placenta was investigated. RT-PCR analysis shows the presence of PPARgamma mRNA in the placenta of day 11 of pregnancy (d11). The expression level is higher at d13 and then later decreased. Immunohistochemistry detects both PPARgamma and its putative intrinsic ligand, 15-deoxy-Delta(12,14)-prostaglandin J(2), in the trophoblast of layer I which lined the maternal sinus. Oral administration of troglitazone, an agonist of PPARgamma, to pregnant rats between d9 and d11 increases the expression level of PPARgamma in the placenta and reduces the mortality of the fetuses by half. These results suggest that PPARgamma is required not only for trophoblast differentiation but also trophoblast maturation to establish maternal-fetal transport.

Administration, Oral↗
PubMed2004

Activators of PPARgamma antagonize protection of cardiac myocytes by endothelin-1.

Endothelin-1 (ET-1) is a potent survival factor against myocardial cell apoptosis. This anti-apoptotic effect of ET-1 is mediated in part through calcineurin/NFATc-dependent induction of bcl-2 expression. Since it has been reported that peroxisome proliferator-activated receptor-gamma (PPARgamma) interacts with NFATc, we investigated the effects of PPARgamma ligands on anti-apoptotic effects of ET-1 in cardiac myocytes. In primary cardiac myocytes from neonatal rats, administration of PPARgamma activators (15-deoxy-delta12,14-prostaglandin J2 and troglitazone) attenuated the anti-apoptotic effects of ET-1. These activators abolished the ET-1-stimulated increase in bcl-2 expression and in binding of cardiac NFATc to the bcl-2 NFAT site. These findings demonstrate that activators of PPARgamma perturb the anti-apoptotic effects of ET-1 in cardiac myocytes and that this perturbation is, in part, based on functional transcriptional cross-talk between NFATc and PPARgamma.

Animals↗
PubMed2004

Pro-inflammatory properties for thiazolidinediones.

Thiazolidinediones (TZDs) are pharmacological ligands of the peroxisome proliferator-activated receptor (PPAR)-gamma that are extensively used in the treatment of type II diabetes. Recently, an anti-inflammatory potential for TZDs has been suggested, based on observations that these compounds may inhibit pro-inflammatory cytokine expression in vitro and may attenuate the inflammatory response in vivo. Here, we show that the TZDs rosiglitazone (RSG) and troglitazone (TRO) do not inhibit the inflammatory response to tumor necrosis factor (TNF)-alpha in various epithelial cell types. On the contrary, both RSG and TRO significantly potentiated TNF-alpha-induced production of granulocyte/macrophage-colony-stimulating factor, interleukin (IL)-6 and/or IL-8 in these cells. This increase in pro-inflammatory cytokine expression was functionally significant as supernatants from cells co-treated with TNF-alpha and TZDs displayed increased neutrophil pro-survival activity when compared with supernatants from cells treated with TNF-alpha alone. Additionally, it was shown that TZDs enhance cytokine expression at the transcriptional level, but that the pro-inflammatory effects of TZDs are independent on PPARgamma, nuclear factor kappaB or mitogen-activated protein kinase activation. Our study shows that TZDs may potentiate the inflammatory response in epithelial cells, a previously unappreciated effect of these compounds.

Cell Line↗
PubMed2005

Modelling cell signalling and differentiation in the urothelium.

Urothelial cells line the bladder. If the urothelium is damaged, it is vital that it repairs itself quickly. Experimental results shedding light on how this repair process works are presented, revealing in particular the dependence of the response on the length of time for which the drug Troglitazone (TZ) is applied. A simple mathematical model for the basic mechanism (comprising ordinary differential equations) is then developed and analysed, seeking specifically to clarify and quantify the mechanisms governing the dependence of the cell differentiation response on the TZ administration time, rather than providing a comprehensive model of differentiation. Through biologically justified simplifications, analysis reveals that the model gives results in accord with the experimental observations, and suggests new experiments that may aid further understanding. Directions in which this preliminary modelling of the PPAR gamma (peroxisome proliferator activated receptor gamma) pathway could be usefully extended are also indicated.

Cell Differentiation↗
PubMed2005

Inhibition of beta-oxidative respiration is a therapeutic window associated with the cancer chemo-preventive activity of PPARgamma agonists.

We demonstrate expression and coordinate induction of PPARgamma and lipogenic enzymes (HMG-CoA synthase, HMG-CoA reductase and fatty acid synthase) in a murine lung alveolar carcinoma cell line (Line 1) treated with the PPARgamma agonist troglitazone (TRO) [0-100 microM]. We postulate that TRO induces a shift in cellular energy metabolism towards fatty acid oxidation (beta-oxidative respiration). Accordingly, co-treatment with TRO [30 microM] and increasing concentrations of trimetazidine (TMZ) [0.1-3 mM], an inhibitor of beta-oxidation, results in a dose dependent decrease cellular ATP levels and a dose dependent induction of apoptosis. These findings, suggest that inhibition of beta-oxidative respiration is a therapeutic window associated with the cancer chemo-preventive activity of PPARgamma agonists.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed2005

Proinflammatory adipocytokines induce TIMP-1 expression in 3T3-L1 adipocytes.

Tissue inhibitor of metalloproteinase (TIMP)-1 is an adipocyte-secreted protein upregulated in obesity which promotes adipose tissue development. Furthermore, the proinflammatory adipocytokines tumor necrosis factor alpha (TNFalpha) and interleukin (IL)-6 induce insulin resistance, and plasma concentrations are increased during weight gain. In the current study, the impact of TNFalpha and IL-6 on TIMP-1 mRNA and protein expression was determined in 3T3-L1 adipocytes. Interestingly, TNFalpha and IL-6 induced TIMP-1 protein secretion more than 3- and 2-fold, respectively. Furthermore, TIMP-1 mRNA was upregulated in a time- and dose-dependent fashion. Inhibitor experiments suggested that nuclear factor kappaB and p 44/42 mitogen-activated protein kinase are involved in both, basal and adipocytokine-induced TIMP-1 expression. Moreover, the thiazolidinedione troglitazone partly reversed TNFalpha- but not IL-6-induced TIMP-1 synthesis. Taken together, we demonstrate that TIMP-1 expression is selectively upregulated in fat cells by proinflammatory adipocytokines and might play a role in maintaining adipose tissue mass in obesity.

3T3-L1 Cells↗
PubMed2005

Peroxisome proliferator-activated receptor-gamma ligands reduce inflammation and infarction size in transient focal ischemia.

Newly developed insulin-sensitizing agents, which target the nuclear receptor peroxisome proliferator-activated receptor-gamma have recently been appreciated to exhibit potent anti-inflammatory actions. Since stroke is associated with an intense inflammatory response, we reasoned that these agents may ameliorate injury from stroke. We report that administration of troglitazone or pioglitazone 24 h before and at the time of cerebral infarction dramatically reduced infarction volume and improved neurological function following middle cerebral artery occlusion in rats. Furthermore, we find that delayed therapy also significantly reduced infarct volume. The brains of the drug-treated animals displayed reduced inflammation as evidenced by decreased immunoreactivity for microglial/macrophage markers and reduced protein and mRNA for interleukin-1beta, cyclooxygenase-2 and inducible nitric oxide synthase. We argue that the beneficial effects of these drugs are likely due to reduced expression of these inflammatory mediators, which are known to exacerbate ischemic injury following stroke. These results are of particular relevance to diabetic patients chronically treated with these agents who may benefit from the neuroprotective actions of these drugs.

Animals↗
PubMed2006

15-Deoxy-12,14-prostaglandin J2 inhibits interferon gamma induced MHC class II but not class I expression on ARPE cells through a PPAR gamma independent mechanism.

Retinal pigment epithelial (RPE) cells constitute the external part of the blood-retinal-barrier and play a pivotal role in the regulation of retinal immunity. In the present work, we investigated the effects of 15-deoxy-12,14-prostaglandin J2 (15 PGJ2), an endogenous ligand of PPARgamma, on the IFNgamma-induced expression of MHC class II on RPE cells. Indeed, pathological expression of MHC class II molecules at the surface of RPE cells is a common feature of many blinding conditions. We demonstrated that 15 PGJ2 inhibited the IFNgamma-mediated induction of MHC class II on RPE cells without affecting the level of MHC class I and CD54 expression. The other PPARgamma agonist rosiglitazone or troglitazone had no similar effects. Moreover, the inhibitory effect of 15 PGJ2 was not abrogated by co-incubation with PPARgamma antagonists and did not involve the modulation of STAT-1, AKT or ERK1/2 phosphorylation, nor CIITA, IRF1 or IRF2 transcription. In conclusion, 15 PGJ2 inhibits strongly and specifically the IFNgamma-induced MHC class II expression on RPE cells by a PPARgamma independent mechanism. Given the differential role of MHC classes I and II in the development of autoimmune uveitis and the potential toxicity of 15 PGJ2, our data's suggest that the development of novel small molecules targeting similar PPARgamma independent pathways would be useful for the future management of uveitis.

Cell Line↗
PubMed2006

PPARgamma activation induces CD36 expression and stimulates foam cell like changes in rVSMCs.

The purpose of the present study was to determine the role of peroxisome proliferator-activated receptor gamma (PPARgamma) activation in smooth muscle cell (SMC) derived form cell formation. Wild and mutant type PPARgamma were delivered by adenovirus then activated with troglitazone. The result of Oil Red O staining and FACS analysis showed that PPARgamma activation induced lipid accumulation in rVSMCs. Furthermore, PPARgamma activation reduced SMC marker genes such as alpha-actin while induced adipocyte differentiation marker genes and lipid metabolism-related genes as evidenced by RT-PCR and fluorescent immunocytochemistry. All these data demonstrate that PPARgamma activation can drive foam cell like change in rVSMCs. Our results strongly suggest that PPARgamma expression induces CD36 expression and adipocyte differentiation gene activation in the process of atherosclerosis and might be one of the crucial events in SMC derived foam cell formation.

ATP Binding Cassette Transporter 1↗
PubMed2004

Simultaneous, bidirectional inhibitory crosstalk between PPAR and STAT5b.

The transcription factors peroxisome proliferator-activated receptor (PPAR) and signal transducer and activator of transcription 5 (STAT5) activate genes involved in fatty acid metabolism (PPARalpha) and adipogenesis (PPARgamma) and mediate hormonal responses important for body growth, liver gene expression, and mammary gland development (STAT5a and STAT5b). These seemingly disparate pathways are subject to mutually inhibitory crosstalk, with growth hormone (GH)-activated STAT5 able to inhibit PPAR-regulated gene transcription by approximately 80%, and conversely, ligand-activated PPAR able to inhibit STAT5-regulated transcription to a similar degree. Given the co-expression of PPAR and STAT5 in multiple tissues, we investigated whether one of the factors dominates the inhibitory crosstalk. A PPAR-responsive Renilla luciferase reporter was constructed and used to monitor PPAR transcriptional activity in COS-1 cells co-transfected with a STAT5 firefly luciferase reporter. In cells co-stimulated with GH and a PPAR agonist, STAT5b inhibited expression of the PPAR-regulated Renilla luciferase reporter, whereas PPARalpha and PPARgamma inhibited transcription of the STAT5b-regulated firefly luciferase reporter. The extent of the inhibitory crosstalk was dependent on the relative levels of expression of each transcription factor and on the relative concentrations of GH and PPAR agonist. Dose-response studies revealed that STAT5b was inhibited at an approximately 7-fold lower concentration of the PPARgamma ligand troglitazone than was required for activation of PPARgamma, indicating that only a portion of cellular PPARgamma is needed for STAT5b inhibition. Similarly, mono-(2-ethylhexyl)phthalate (MEHP), a reproductive toxicant and primary metabolite of the environmental chemical di-(2-ethylhexyl)phthalate (DEHP), inhibited STAT5b transcriptional activity with an EC50 value of 1.1 microM, corresponding to an approximately 10-fold lower concentration than required for activation of PPARgamma-dependent transcription. We conclude that the cross-inhibition between PPAR and STAT5 proceeds in a simultaneous, bidirectional manner. Exposure to phthalates and other environmental chemical activators of PPARs may thus lead to alteration of hormone-induced, STAT5-regulated gene expression in tissues such as liver, fat and breast, where both transcription factors are expressed. Conversely, STAT5-activating hormones and cytokines may modulate the responsiveness of PPARs to their foreign chemical ligands.

Animals↗
PubMed2006

Activation of peroxisome proliferator-activated receptor-gamma (PPARgamma) induces cell death through MAPK-dependent mechanism in osteoblastic cells.

The present study was undertaken to determine the role of the mitogen-activated protein kinase (MAPK) subfamilies in cell death induced by PPARgamma agonists in osteoblastic cells. Ciglitazone and troglitazone, PPARgamma agonists, resulted in a concentration- and time-dependent cell death, which was largely attributed to apoptosis. But a PPARalpha agonist ciprofibrate did not affect the cell death. Ciglitazone caused reactive oxygen species (ROS) generation and ciglitazone-induced cell death was prevented by antioxidants, suggesting an important role of ROS generation in the ciglitazone-induced cell death. ROS generation and cell death induced by ciglitazone were inhibited by the PPARgamma antagonist GW9662. Ciglitazone treatment caused activation of extracellular signal-regulated kinase (ERK) and p38. Activation of ERK was dependent on epidermal growth factor receptor (EGFR) and that of p38 was independent. Ciglitazone-induced cell death was significantly prevented by PD98059, an inhibitor of ERK upstream kinase MEK1/2, and SB203580, a p38 inhibitor. Ciglitazone treatment increased Bax expression and caused a loss of mitochondrial membrane potential, and its effect was prevented by N-acetylcysteine, PD98059, and SB203580. Ciglitazone induced caspase activation, which was prevented by PD98059 and SB203580. The general caspase inhibitor z-DEVD-FMK and the specific inhibitor of caspases-3 DEVD-CHO exerted the protective effect against the ciglitazone-induced cell death. The EGFR inhibitors AG1478 and suramin protected against the ciglitazone-induced cell death. Taken together, these findings suggest that the MAPK signaling pathways play an active role in mediating the ciglitazone-induced cell death of osteoblasts and function upstream of a mitochondria-dependent mechanism. These data may provide a novel insight into potential therapeutic strategies for treatment of osteoporosis.

3T3 Cells↗
PubMed2005

Peroxisome-proliferator-activated receptor-gamma agonists inhibit the release of proinflammatory cytokines from RSV-infected epithelial cells.

The epithelial cells of the airways are the target cells for respiratory syncytial virus (RSV) infection and the site of the majority of the inflammation associated with the disease. Recently, peroxisome-proliferator-activated receptor gamma (PPARgamma), a member of the nuclear hormone receptor superfamily, has been shown to possess anti-inflammatory properties. Therefore, we investigated the role of PPARgamma agonists (15d-PGJ(2), ciglitazone and troglitazone) on the synthesis of RSV-induced cytokine release from RSV-infected human lung epithelial cells (A549). We observed that all PPARgamma ligands inhibited dose-dependently the release of TNF-alpha, GM-CSF, IL-1alpha, IL-6 and the chemokines CXCL8 (IL-8) and CCL5 (RANTES) from RSV-infected A549 cells. Concomitantly, the PPARgamma ligands diminished the cellular amount of mRNA encoding for IL-6, CXCL8 and CCL5 and the RSV-induced binding activity of the transcription factors NF-kappaB (p65/p50) and AP-1 (c-fos), respectively. Our data presented herein suggest a potential application of PPARgamma ligands in the anti-inflammatory treatment of RSV infection.

Cell Line, Tumor↗
PubMed2006

Peroxisome proliferator-activated receptor-gamma agonists inhibit the replication of respiratory syncytial virus (RSV) in human lung epithelial cells.

We have previously shown that peroxisome proliferator-activated receptor-gamma (PPARgamma) agonists inhibited the inflammatory response of RSV-infected human lung epithelial cells. In this study, we supply evidence that specific PPARgamma agonists (15d-PGJ2, ciglitazone, troglitazone, Fmoc-Leu) efficiently blocked the RSV-induced cytotoxicity and development of syncytia in tissue culture (A549, HEp-2). All PPARgamma agonists under study markedly inhibited the cell surface expression of the viral G and F protein on RSV-infected A549 cells. This was paralleled by a reduced cellular amount of N protein-encoding mRNA determined by real-time RT-PCR. Concomitantly, a reduced release of infectious progeny virus into the cell supernatants of human lung epithelial cells (A549, normal human bronchial epithelial cells (NHBE)) was observed. Similar results were obtained regardless whether PPARgamma agonists were added prior to RSV infection or thereafter, suggesting that the agonists inhibited viral gene expression and not the primary adhesion or fusion process.

Chromans↗
PubMed2006

Peroxisome proliferator-activated receptor gamma regulates expression of signal transducer and activator of transcription 5A.

Signal transducer and activator of transcription 5A (STAT5A) has been shown to be important for terminal differentiation of mammary epithelial cells. In order to understand regulation of expression of STAT5A, the 5' end of the mouse Stat5a gene was isolated. Putative regulatory elements was searched for and several peroxisome proliferator response elements (PPREs) were found, one with high (12/13 nucleotides) and three with less (8-10/13) similarity to the reported consensus sequence. Mouse mammary epithelial HC11 cells were treated with peroxisome proliferator-activated receptor gamma (PPARgamma) ligand, the thiazolidinedione (TZD) troglitazone, and an increase in STAT5A protein expression was seen. The 5' flank of Stat5a gene was cloned in a luciferase reporter vector. A concentration dependent activation of the STAT5A-luciferase reporter was detected, when transiently transfected HC11 cells were treated with TZD. The activation could be inhibited by treatment with a PPARgamma antagonist. It has earlier been shown that epidermal growth factor (EGF) induces MAPK phosphorylation of PPARgamma resulting in a less transcriptionally active receptor. In HC11 cells, EGF inhibited TZD induced STAT5A-reporter activity suggesting that our previously reported EGF-mediated suppression of STAT5A expression is mediated in all or partly through inhibition of PPARgamma activity. Furthermore, the MEK inhibitor PD98059 inhibited the EGF effect. All together, data presented suggest that PPARgamma participates in regulation of STAT5A expression.

5' Flanking Region↗
PubMed2001

Role of peroxisome proliferator-activated receptor gamma and its ligands in non-neoplastic and neoplastic human urothelial cells.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear receptor superfamily of ligand-activated transcription factors and is expressed in several types of tissue. Although PPARgamma reportedly is expressed in normal urothelium, its function is unknown. We examined the expression of PPARgamma in normal urothelium and bladder cancer in an attempt to assess its functional role. Immunohistochemical staining revealed normal urothelium to express PPARgamma uniformly. All low-grade carcinomas were positive either diffusely or focally, whereas staining was primarily focal or absent in high-grade carcinomas. A nonneoplastic urothelial cell line (1T-1), a low-grade (RT4) carcinoma cell line, and two high-grade (T24 and 253J) carcinoma cell lines in culture expressed PPARgamma mRNA and protein. Luciferase assay indicated that PPARgamma was functional. PPARgamma ligands (15-deoxy-Delta(12,14)-prostaglandin J(2), troglitazone and pioglitazone) suppressed the growth of nonneoplastic and neoplastic urothelial cells in a dose-dependent manner. However, neoplastic cells were more resistant than were nonneoplastic cells. Failure to express PPARgamma or ineffective transcriptional activity may be some of the mechanisms responsible for resistance to the inhibitory action of PPARgamma ligands.

Aged↗
PubMed2004

Activation of peroxisome proliferator-activated receptor-gamma reverses squamous metaplasia and induces transitional differentiation in normal human urothelial cells.

We observed that in urothelium, both cornifying and noncornifying forms of squamous metaplasia are accompanied by changes in the localization of the nuclear hormone receptors, peroxisome proliferator activated receptor gamma (PPAR-gamma) and retinoid X receptor (RXR-alpha). To obtain objective evidence for a role for PPAR-gamma-mediated signaling in urothelial differentiation, we examined expression of the cytokeratin isotypes CK13, CK20, and CK14 as indicators of transitional, terminal transitional, and squamous differentiation, respectively, in cultures of normal human urothelial cells. In control culture conditions, normal human urothelial cells showed evidence of squamous differentiation (CK14+, CK13-, CK20-). Treatment with the high-affinity PPAR-gamma agonist, troglitazone (TZ), resulted in gain of CK13 and loss of CK14 protein expression. The effect of TZ was significantly augmented when the autocrine-stimulated epidermal growth factor receptor pathway was inhibited and this resulted in induction of CK20 expression. The RXR-specific inhibitors PA452, HX531, and HX603 inhibited the TZ-induced CK13 expression, supporting a role for RXR in the induction of CK13 expression. Thus, signaling through PPAR-gamma can mediate transitional differentiation of urothelial cells and this is modulated by growth regulatory programs.

Cell Differentiation↗
PubMed2002

Rat liver acyl-CoA synthetase 4 is a peripheral-membrane protein located in two distinct subcellular organelles, peroxisomes, and mitochondrial-associated membrane.

Obesity and non-insulin-dependent diabetes favor storage of fatty acids in triacylglycerol over oxidation. Recently, individual acyl-CoA synthetase (ACS) isoforms have been implicated in the channeling of fatty acids either toward lipid synthesis or toward oxidation. Although ACS1 had been localized to three different subcellular regions in rat liver, endoplasmic reticulum, mitochondria, and peroxisomes, the study had used an antibody raised against the full-length ACS1 protein which cross-reacts with other isoforms, probably because all ACS family members contain highly conserved amino acid sequences. Therefore, we examined the subcellular location of ACS1, ACS4, and ACS5 in rat liver to determine which isoform was present in peroxisomes, whether the ACSs were intrinsic membrane proteins, and which ACS isoforms were up-regulated by PPAR alpha ligands. Non-cross-reacting ACS1, ACS4, and ACS5 peptide antibodies showed that ACS4 was the only ACS isoform present in peroxisomes isolated from livers of gemfibrozil-treated rats. ACS4 was also present in fractions identified as mitochondria-associated membrane (MAM). ACS1 was present in endoplasmic reticulum fractions and ACS5 was present in mitochondrial fractions. Incubation with troglitazone, a specific inhibitor of ACS4, decreased ACS activity in the MAM fractions 30-45% and in the peroxisomal fractions about 30%. Because the signal for ACS4 protein in peroxisomes was so strong compared to the MAM fraction, we examined ACS4 mRNA abundance in livers of rats treated with the PPAR alpha agonist GW9578. Treatment with GW9578 increased ACS4 mRNA abundance 40% and ACS1 mRNA 25%. Although we had originally proposed that ACS4 is linked to triacylglycerol synthesis, it now appears that ACS4 may also be important in activating fatty acids destined for peroxisomal oxidation. We also determined that, unlike ACS1 and 5, ACS4 is not an intrinsic membrane protein. This suggests that ACS4 is probably targeted and linked to MAM and peroxisomes by interactions with other proteins.

Animals↗