Prostaglandins & other lipid mediators最新文献

{"title":"Cilostazol induces vasorelaxation through the activation of the eNOS/NO/cGMP pathway, prostanoids, AMPK, PKC, potassium channels, and calcium channels","authors":"Serdar Sahinturk","doi":"10.1016/j.prostaglandins.2023.106782","DOIUrl":"10.1016/j.prostaglandins.2023.106782","url":null,"abstract":"<div><h3>Objective</h3><p>This study aimed to investigate vasoactive effect mechanisms of cilostazol in rat thoracic aorta.</p></div><div><h3>Materials and methods</h3><p><span>The vessel rings prepared from the thoracic aortas of the male rats were placed in the chambers of the isolated tissue bath system. The resting tone was adjusted to 1 g. Following the equilibration phase, potassium chloride or phenylephrine was used to contract the vessel rings. When achieving a steady contraction, cilostazol was applied cumulatively (10</span>⁻⁸–10⁻⁴<span><span> M). In the presence of potassium channel blockers or </span>signaling pathway inhibitors, the same experimental procedure was performed.</span></p></div><div><h3>Results</h3><p>Cilostazol exhibited a significant vasorelaxant effect in a concentration-dependent manner (pD2: 5.94 ± 0.94) (p &lt; .001). The vasorelaxant effect level of cilostazol was significantly reduced by the endothelial nitric oxide synthase inhibitor <span>L</span>-NAME (10⁻⁴<span><span> M), soluble guanylate cyclase<span> inhibitor methylene blue (10 µM), </span></span>cyclooxygenase<span> 1/2 inhibitor indomethacin (5 µM), adenosine monophosphate-activated protein kinase inhibitor compound C (10 µM), non-selective potassium channel blocker tetraethylammonium chloride (10 mM), large-conductance calcium-activated potassium channel blocker iberiotoxin (20 nM), voltage-gated potassium channel blocker 4-Aminopyridine (1 mM), and inward-rectifier potassium channel blocker BaCl</span></span>₂ (30 µM) (p &lt; .001). Moreover, incubation of cilostazol (10⁻⁴ M) significantly reduced caffeine (10 mM), cyclopiazonic acid (10 µM), and phorbol 12-myristate 13-acetate-induced (100 µM) vascular contractions (p &lt; .001).</p></div><div><h3>Conclusions</h3><p>In the rat thoracic aorta, the vasodilator action level of cilostazol is quite noticeable. The vasorelaxant effects of cilostazol are mediated by the eNOS/NO/cGMP pathway, prostanoids<span>, AMPK<span> pathway, PKC, potassium channels<span>, and calcium channels.</span></span></span></p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41150203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Follistatin and follistatin-like 3 in metabolic disorders","authors":"Weronika Bielka ,&nbsp;Agnieszka Przezak ,&nbsp;Andrzej Pawlik","doi":"10.1016/j.prostaglandins.2023.106785","DOIUrl":"10.1016/j.prostaglandins.2023.106785","url":null,"abstract":"<div><p>Follistatin (FST) is a glycoprotein which main role is antagonizing activity of transforming growth factor β superfamily members. Folistatin-related proteins such as follistatin-like 3 (FSTL3) also reveal these properties. The exact function of them has still not been established, but it can be bound to the pathogenesis of metabolic disorders. So far, there were performed a few studies about their role in type 2 diabetes, obesity or gestational diabetes and even less in type 1 diabetes. The outcomes are contradictory and do not allow to draw exact conclusions. In this article we summarize the available information about connections between follistatin, as well as follistatin-like 3, and metabolic disorders. We also emphasize the strong need of performing further research to explain their exact role, especially in the pathogenesis of diabetes and obesity.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41128695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Uterodilation effect of unripe fruit extract of Crataegus azarolus var. aronia L. on rat uterine smooth muscles","authors":"Aveen Abdullah Mohammed Ameen","doi":"10.1016/j.prostaglandins.2023.106783","DOIUrl":"10.1016/j.prostaglandins.2023.106783","url":null,"abstract":"<div><p><span><em>Crataegus azarolus var. </em><em>aronia</em></span> L. (<em>C. aronia</em><span>) is one of the most important medicinal plants<span> used widely in folk medicine for the prevention of several diseases due to its content of several bioactive compounds like phenolic acid, aromatic amines, proanthocyanidins<span> and flavonoids. This study investigated the uterodilation effect of methanol extract (ME) of </span></span></span><em>C. aronia</em><span><span> unripe fruit on the uterine smooth muscle in rats. The mechanism of action underlying the plant's extract was also screened. The unripe fruits were cleaned and extracted in methanol. The extract (1.9–4 mg/ml) was tested on rat uterine relaxation in calcium-free Kreb's solution and potassium chloride-induced </span>uterine contraction<span><span>. The plant extract was also studied in the presence of antagonists in separate experiments to determine the role of various ion channels and hyperpolarizing agents. The plant extract showed an uterodilation effect on the uterus, in which the ME produced a considerable relaxant effect. The results confirmed that the induced dilation was mediated mainly by the nitric oxide pathway and the activation of </span>potassium channels<span><span> with a limited role of the prostaglandin pathway and </span>calcium channel activation. This in-vitro study provides the first scientific evidence of the claimed effect of </span></span></span><em>C. aronia</em> on uterine relaxation.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41139471","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Co-administration of curcumin and polyamines in high-fat diet induced obese rats: Assessment of changes in serum polyamine levels and some tissue parameters","authors":"Gözde Dumlu Bilgin ,&nbsp;Nihal Büyükuslu ,&nbsp;Ozan Emre Eyüpoğlu ,&nbsp;Alev Cumbul","doi":"10.1016/j.prostaglandins.2023.106784","DOIUrl":"10.1016/j.prostaglandins.2023.106784","url":null,"abstract":"<div><p><span>Obesity is a non-communicable chronic disease that continues to increase around the world. Recently, it has been shown that curcumin positively affects lipid<span><span>, energy metabolism, and body weight change. Moreover, polyamines are aliphatic polycations, which can be found in all </span>mammalian cells and foods and have been shown to prevent obesity through many different mechanisms. However, whether the co-administration of curcumin and polyamines has synergistic effects has yet to be clarified. Our study aimed to examine the effects of curcumin and polyamines on obesity and to assess the changes in serum polyamine levels and tissue parameters. 28 Sprague-Dawley male rats were fed a high-fat diet for 10 weeks to develop obesity, and then they were randomly divided into 4 groups as the control group (CONT), curcumin group (CUR), polyamine group (POL), curcumin and polyamine group (CUR+POL) and supplements were administered for 6 weeks. As a result, the lowest feed consumption in rats was recorded in the CUR+POL group, and the group with the lowest weight after supplements was the POL group, then the CUR+POL, CONT, and CUR groups, respectively. N-acetyl putrescine and </span></span>GABA levels increased significantly after obesity development. The total histopathological score in fat, liver, and kidney tissues increased significantly in the CONT group. In the CUR+POL group, damage to the tissues was in the direction of recovery compared to the other groups, and the expression of NF-κB was significantly low. These results suggest that combined curcumin and polyamines may have protective effects.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41154073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioinformatics analysis identifies the protective targets of omentin in mice with focal cerebral ischemia injury","authors":"Wu Li ,&nbsp;Jie Liu ,&nbsp;Qi Zhang ,&nbsp;Xiaojuan Ma ,&nbsp;Jinwei Duan ,&nbsp;Jiachen Wang ,&nbsp;Ye Tian ,&nbsp;Wenzhen Shi","doi":"10.1016/j.prostaglandins.2023.106780","DOIUrl":"10.1016/j.prostaglandins.2023.106780","url":null,"abstract":"<div><p><span><span>Omentin is known to play a protective role in ischemic stroke. However, its regulatory networks and downstream targets in the pathogenesis of IS are incompletely revealed now. In this study, the model of photochemical brain ischemia was constructed after omentin over-expression. 8 key differentially expressed genes (DEGs) were obtained and analyzed by transcriptome analysis. These DEGs were mainly related to the negative regulation of hormone secretion, cellular phosphate ion </span>homeostasis<span>, and other pathways. Moreover, the mRNA expression of predicted gene 3435 (Gm3435), ankyrin repeat domain 53 (Ankrd53), </span></span>fibroblast growth factor 23<span> (Fgf23) and the Fgf23 protein expression<span> were down-regulated after omentin over-expression in HT22 cells injured by oxygen-glucose deprivation (OGD). In conclusion, our findings identified 8 key DEGs regulated by omentin after IS. In vitro models, the Gm3435, Ankrd53, Fgf23 mRNA expression and the Fgf23 protein expression were further verified to consistent with the transcriptomics results.</span></span></p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10285708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imbalanced serum levels of resolvin E1 (RvE1) and leukotriene B4 (LTB4) may contribute to the pathogenesis of atherosclerosis","authors":"Mohsen Molaie ,&nbsp;Ramin Lotfi ,&nbsp;Reza Heidari Moghadam ,&nbsp;Alireza Rezaiemanesh ,&nbsp;Ali Gorgin Karaji ,&nbsp;Farhad Salari","doi":"10.1016/j.prostaglandins.2023.106781","DOIUrl":"10.1016/j.prostaglandins.2023.106781","url":null,"abstract":"<div><p><span><span>Persistent and chronic unresolved inflammation exerts a critical role in developing atherosclerosis; however, mechanisms that prevent the resolution of inflammation in atherosclerosis are poorly delineated. This study aims to evaluate the serum levels of inflammatory high-sensitivity C-reactive protein (hsCRP), pro-inflammatory leukotriene B4 (LTB4), besides anti-inflammatory compounds, including </span>eicosapentaenoic acid (EPA) and its derivative resolvin E1 (RvE1) in patients with atherosclerosis. Thirty-four atherosclerosis patients and thirty-two age- and sex-matched healthy individuals were included in this study. The serum levels of hsCRP, LTB4, EPA, and RvE1 were measured using the enzyme-linked immunosorbent assay (ELISA) technique. Our results showed that the hsCRP serum levels in the three-vessel disease (3VD) subgroup of patients are significantly lower than those in the mild and single-vessel disease (SVD) subgroups (</span><em>P</em> &lt; 0.05). Besides, the serum levels of LTB4 were meaningfully greater in patients with atherosclerosis compared to healthy controls (<em>P</em> &lt; 0.05). Also, the serum EPA and RvE1 levels were significantly higher in patients than in controls (<em>P</em> &lt; 0.01 and <em>P</em> &lt; 0.05, respectively). However, the ratio of RvE1 to LTB4 (RvE1:LTB4) in patients was significantly reduced to that in controls (<em>P</em> &lt; 0.0001). These findings illustrate that imbalanced pro-resolving RvE1 and pro-inflammatory LTB4 might contribute to failing vascular inflammation resolution and subsequent progression toward chronic inflammation in atherosclerosis.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10285712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostaglandin D2 regulates Escherichia coli-induced inflammatory responses through TLR2, TLR4, and NLRP3 in macrophages","authors":"Zhiguo Gong ,&nbsp;Wei Mao ,&nbsp;Feng Jin ,&nbsp;Shuangyi Zhang ,&nbsp;Jiamin Zhao ,&nbsp;Peipei Ren ,&nbsp;Zhuoya Yu ,&nbsp;Yunjie Bai ,&nbsp;Chao Wang ,&nbsp;Jinshan Cao ,&nbsp;Bo Liu","doi":"10.1016/j.prostaglandins.2023.106772","DOIUrl":"https://doi.org/10.1016/j.prostaglandins.2023.106772","url":null,"abstract":"<div><p>Prostaglandin D₂ (PGD₂<span>) synthesis is closely associated with the innate immune response mediated by pattern recognition receptors (PPRs). We determined PGD</span>₂ synthesis whether mediated by Toll-like receptor 2 (TLR2), TLR4 and Nod-like receptor pyrin domain-containing protein 3 (NLRP3) in <em>Escherichia coli</em> (<em>E. coli</em><span>)-, lipopolysaccharide (LPS)- and Braun lipoprotein (BLP)-stimulated macrophages. Our data demonstrate that TLR2, TLR4, and NLRP3 could regulate the synthesis of PGD</span>₂<span> through cyclo-oxygenase-2 (COX-2) and hematopoietic PGD synthase (H-PGDS) in </span><em>E. coli</em>-, LPS- or BLP-stimulated macrophages, suggesting that TLR2, TLR4, and NLRP3 are critical in regulating PGD₂ secretion by controlling PGD₂ synthetase expression in <em>E. coli</em>-, LPS- or BLP-stimulated macrophages. The H-PGDS (a PGD₂ specific synthase) inhibitor pre-treatment could down-regulate the secretion of TNF-α, RANTES and IL-10 in LPS- and <em>E. coli-</em>stimulated macrophage. Meanwhile, H-PGDS inhibitor could down-regulate the secretion of TNF-α, while up-regulated RANTES and IL-10 secretion in BLP-stimulated macrophages, suggesting that PGD₂<span> could regulate the secretion of cytokines and chemokines in </span><em>E. coli</em>-, LPS- or BLP-stimulated macrophages. Furthermore, exogenous PGD₂<span><span> regulates the secretion of cytokines and chemokines through activation of MAPK and NF-κB </span>signaling pathways after </span><em>E. coli</em>-, LPS- or BLP stimulation in macrophages. Taken together, PGD₂ is found able to regulate <em>E. coli</em>-induced inflammatory responses through TLR2, TLR4, and NLRP3 in macrophages.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49855755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding interactions of fatty acyl lipid mediators within the vanilloid pocket of TRPV1: A molecular dynamics study","authors":"Nada Birkic ,&nbsp;David Visentin ,&nbsp;Željko Svedružić ,&nbsp;Christian A. Reynolds","doi":"10.1016/j.prostaglandins.2023.106771","DOIUrl":"10.1016/j.prostaglandins.2023.106771","url":null,"abstract":"<div><p><span><span>The transient receptor potential<span><span> vanilloid 1 (TRPV1) channel is a ligand-gated, nonselective cation channel expressed in primary sensory neurons, which has a role in </span>nociception<span>. The channel is activated by noxious heat, pH, capsaicin and other endogenous vanilloids, including lipid mediators (LMs) enzymatically derived from polyunsaturated fatty acids (PUFA). Although capsaicin binding to TRPV1 has been well characterized, the molecular mechanism by which endogenous LM ligands bind the channel is not well understood. In this study, we characterized the binding interactions for 13 endogenous LM ligands, within the vanilloid pocket of TRPV1 using a molecular dynamics (MD) approach. We observed that LM ligands can be grouped based on their structure and affinity for the vanilloid pocket. Furthermore, the position as well as the number of the polar groups on the LM ligand directly impact binding stability through various polar interactions with the protein. As an additional control we performed docking experiments of the PUFA precursor molecules </span></span></span>linoleic acid<span> and arachidonic acid which failed to form stable interactions within the vanilloid pocket. While LM ligands with similar structures displayed similar binding interactions, there were notable exceptions in the case of 20-HETE, 9-HODE, and 9,10-DiHOME. Our study offers new insights into the mechanisms involved in TRPV1 activation by endogenous LM ligands. The observed binding interactions may assist in the interpretation of </span></span><em>in vivo</em> and <em>in vitro</em><span> pharmacodynamics studies.</span></p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10304567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effect of SARS-CoV-2 variants on the plasma oxylipins and PUFAs of COVID-19 patients","authors":"Denise Biagini ,&nbsp;Paolo Oliveri ,&nbsp;Andreina Baj ,&nbsp;Daniela Dalla Gasperina ,&nbsp;Francesca Drago Ferrante ,&nbsp;Tommaso Lomonaco ,&nbsp;Silvia Ghimenti ,&nbsp;Alessio Lenzi ,&nbsp;Andrea Bonini ,&nbsp;Federico Vivaldi ,&nbsp;Camille Oger ,&nbsp;Jean-Marie Galano ,&nbsp;Laurence Balas ,&nbsp;Thierry Durand ,&nbsp;Fabrizio Maggi ,&nbsp;Fabio Di Francesco","doi":"10.1016/j.prostaglandins.2023.106770","DOIUrl":"10.1016/j.prostaglandins.2023.106770","url":null,"abstract":"<div><p>Oxylipins are important signalling compounds that are significantly involved in the regulation of the immune system and the resolution of inflammation. Lipid metabolism is strongly activated upon SARS-CoV-2 infection, however the modulating effects of oxylipins induced by different variants remain unexplored.</p><p>Here, we compare the plasma profiles of thirty-seven oxylipins and four PUFAs in subjects infected with Wild-type, Alpha (B.1.1.7), Delta (B.1.617.2), and Omicron (B.1.1.529) variants.</p><p>The results suggest that oxidative stress<span> and inflammation resulting from COVID-19 were highly dependent on the SARS-CoV-2 variant, and that the Wild-type elicited the strongest inflammatory storm. The Alpha and Delta variants induced a comparable lipid profile alteration upon infection, which differed significantly from Omicron. The latter variant increased the levels of pro-inflammatory mediators and decreased the levels of omega-3 PUFA in infected patients.</span></p><p>We speculate that changes in therapeutics, vaccination, and prior infections may have a role in the alteration of the oxylipin profile besides viral mutations. The results shed new light on the evolution of the inflammatory response in COVID-19.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10110423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel HSPB1S139F mouse model of Charcot-Marie-Tooth Disease","authors":"Keila S. Espinoza ,&nbsp;Kyra N. Hermanson ,&nbsp;Cameron A. Beard ,&nbsp;Nicholas U. Schwartz ,&nbsp;Justin M. Snider ,&nbsp;Benjamin E. Low ,&nbsp;Michael V. Wiles ,&nbsp;Yusuf A. Hannun ,&nbsp;Lina M. Obeid ,&nbsp;Ashley J. Snider","doi":"10.1016/j.prostaglandins.2023.106769","DOIUrl":"https://doi.org/10.1016/j.prostaglandins.2023.106769","url":null,"abstract":"<div><p><span><span>Charcot-Marie-Tooth Disease (CMT) is a commonly inherited peripheral polyneuropathy. Clinical manifestations for this disease include symmetrical distal polyneuropathy, altered deep tendon reflexes, distal sensory loss, foot deformities, and gait abnormalities. </span>Genetic mutations<span> in heat shock proteins have been linked to CMT2. Specifically, mutations in the heat shock protein B1 (</span></span><em>HSPB1</em>) gene encoding for heat shock protein 27 (Hsp27) have been linked to CMT2F and distal hereditary motor and sensory neuropathy type 2B (dHMSN2B) subtype. The goal of the study was to examine the role of an endogenous mutation in HSPB1 <em>in vivo</em><span> and to define the effects of this mutation on motor function and pathology in a novel animal model<span><span>. As sphingolipids have been implicated in hereditary and sensory neuropathies, we examined </span>sphingolipid metabolism in central and peripheral nervous tissues in 3-month-old Hsp</span></span>^S139F mice. Though sphingolipid levels were not altered in sciatic nerves from Hsp^S139F<span> mice, ceramides<span> and deoxyceramides, as well as sphingomyelins (SMs) were elevated in brain tissues from Hsp</span></span>^S139F mice. Histology was utilized to further characterize Hsp^S139F mice. Hsp^S139F<span> mice exhibited no alterations to the expression and phosphorylation of neurofilaments, or in the expression of acetylated α-tubulin in the brain or sciatic nerve. Interestingly, Hsp</span>^S139F mice demonstrated cerebellar demyelination. Locomotor function, grip strength and gait were examined to define the role of Hsp^S139F in the clinical phenotypes associated with CMT2F. Gait analysis revealed no differences between Hsp^WT and Hsp^S139F mice. However, both coordination and grip strength were decreased in 3-month-old Hsp^S139F mice. Together these data suggest that the endogenous S139F mutation in HSPB1 may serve as a mouse model for hereditary and sensory neuropathies such as CMT2F.</p></div>","PeriodicalId":21161,"journal":{"name":"Prostaglandins & other lipid mediators","volume":null,"pages":null},"PeriodicalIF":2.9,"publicationDate":"2023-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49855758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}