Journal of biochemical and pharmacological research最新文献

{"title":"Expression of synaptophysin protein in different dopaminergic cell lines.","authors":"Xiang Bai,&nbsp;Randy Strong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Synaptophysin is a specific presynaptic marker for neurons. Loss of synaptophysin occurs in Parkinson's disease, dementia with Lewy bodies and other neurodegenerative diseases. <i>In vitro</i> studies on synaptophysin are important to understand both the function of the protein itself and its implication in the pathogenesis of neurological diseases. In this study, we determined synaptophysin protein expression by Western analysis in 6 different dopaminergic cell lines including one human (SH-SY5Y), two rat (PC12 and N27) and 3 mouse (MN9D, Cath.a and CAD) cell lines. We found that synaptophysin protein is richly expressed in PC12 cells, but much less in other cells we studied. The order of synaptophysin expression from high to low for the other 5 cell lines was CAD> SH-SY5Y> MN9D> Cath.a = N27 cells, with Cath.a and N27 cells expressing almost undetectable content of synaptophysin protein. These data may be useful to other researchers in choosing a dopaminergic cell line as a model system to study the pathophysiology of neuron terminal loss.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"2 4","pages":"185-190"},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4536951/pdf/nihms699887.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34097152","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":"Excipients of preservative-free latanoprost induced inflammatory response and cytotoxicity in immortalized human HCE-2 corneal epithelial cells.","authors":"Adrian Smedowski,&nbsp;Jussi J Paterno,&nbsp;Elisa Toropainen,&nbsp;Debasish Sinha,&nbsp;Edward Wylegala,&nbsp;Kai Kaarniranta","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Various preservative-free eye drop formulations for glaucoma treatment have been marketed intending to decrease ocular surface side effects and improve tolerability. However, preservative-free eye drops including different solubilizers to dissolve the antiglaucoma drugs may induce detrimental effects in the eye. In this study, we exposed human corneal epithelial cells (HCE-2) for 1, 6, 12, 24 and 48 hours to the first preservative-free (PF) tafluprost (Taflotan^®), the recently-launched preservative-free (PF) latanoprost (Monoprost^®), preservative benzalkonium chloride (BAK) and the excipient macrogolglycerol hydroxystearate 40 (MGHS40) using dilutions 0.1%, 0.3%, 1.0%, 3.0% and 10.0% of the original products. The cells also were exposed to undiluted PF tafluprost and PF latanoprost once a day for 9 days. Cellular morphology was examined by light microscopy and cell proliferation by Ki-67 fluorescent staining with cell viability being determined by erythrosine staining and the release of lactate dehydrogenase (LDH). Mitochondrial metabolic activity was evaluated with the colorimetric MTT assay. The secretion of interleukin 6 (IL-6) was measured with ELISA. HCE-2 cells displayed no significant morphological changes after PF tafluprost treatment, but PF latanoprost caused clear cell loss. Moreover, PF latanoprost, BAK and MGHS40 evoked cellular damage and inflammation with increasing concentrations and time. Furthermore, undiluted daily PF latanoprost application significantly increased LDH release and IL-6 secretion as compared to PF tafluprost. MGHS40 was observed to be associated with the toxicity of PF latanoprost. Excipients in ocular drops should receive more attention in the future, since they seem to trigger similar detrimental effects in cells as preservatives.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"2 4","pages":"175-184"},"PeriodicalIF":0.0,"publicationDate":"2014-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4270205/pdf/nihms-627174.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32927173","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":"A new mouse model to study compensatory mechanisms that support normal motor function in Parkinson's disease.","authors":"Xiang Bai,&nbsp;Stacy A Hussong","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"2 2","pages":"54-56"},"PeriodicalIF":0.0,"publicationDate":"2014-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4578241/pdf/nihms701936.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34032824","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":"Homozygous Deletion of Glutathione Peroxidase 1 and Aldehyde Dehydrogenase 1a1 Genes Is Not Associated with Schizophrenia-Like Behavior in Mice.","authors":"Xiang Bai, Elizabeth Fermandez, Georgianna Gould, Randy Strong","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Much evidence suggests that oxidative stress plays a role in schizophrenia pathogenesis. Major oxidative stress sources include hydrogen peroxide and biogenic aldehydes that are mainly cleared <i>in vivo</i> by glutathione peroxidase (GPX) and aldehyde dehydrogenase (ALDH), respectively. Both enzymes are richly expressed in brain. Schizophrenia patients have significantly increased plasma levels of malondialdehyde and glutathione, combined with decreased GPX activity and ALDH1 mRNA levels in the ventral tegmental area. Absence of Aldh1a1 (murine homolog of ALDH1) gene causes increased basal extracellular dopamine concentrations, a common characteristic of schizophrenia. Studies investigating association between gene polymorphisms of GPX1 (the most abundant form of GPX) or ALDH1A1 with schizophrenia also have not clearly demonstrated whether ALDH1A1 or GPX1 is involved in pathogenesis of schizophrenia. To investigate possible contributions of ALDH and GPX to pathological behaviors associated with schizophrenia, we generated mice with both Aldh1a1 and Gpx1 gene deletions (KO). Aldh1a1/Gpx1 KO and wild type (WT) mice had similar number of novel entry and alteration in Y-maze test, suggesting no cognition deficit in KO. Furthermore, KO and WT displayed similar social interaction and novelty preferences in three chambered tests. Overall, KO and WT had similar activity levels, as indicated by their entries in the Y-maze and sociability tests. Furthermore both genotypes buried a similar percentage of marbles in a 30 min marble-burying task. In summary, homozygous deletion of Gpx1 and Aldh1a1 genes was not associated with schizophrenia-like behavioral phenotypes including anxiety, hyperactivity, cognitive deficit or social disability. Our findings suggest that constitutive absence of these genes alone is unlikely to give rise to common behavioral schizophrenia symptoms. However, these mice may be highly sensitive to oxidative challenges during critical stages of prenatal or juvenile brain development.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 4","pages":"228-235"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3909525/pdf/nihms548875.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32088020","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":"3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a Selective Antagonist of Sphingosine-1-phospahte Receptor Subtype 1, Enhances AMD3100-stimulated Mobilization of Hematopoietic Stem Progenitor Cells in Animals.","authors":"Jingjing Liu,&nbsp;Jiawei Zhao,&nbsp;Jen-Fu Lee,&nbsp;Allison Gartung,&nbsp;Hiba Jawadi,&nbsp;Wenliang Zhang,&nbsp;David Lominadze,&nbsp;Menq-Jer Lee","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Sphingosine-1-phosphate (S1P), a serum-borne bioactive lipid, regulates various physiological functions. We observed that the S1P receptor subtype 1 (S1P₁), a high affinity G-protein coupled receptor of S1P, is the major S1P receptor expressed in the Kit⁺/Sca-1⁺/Lin^- (KSL) hematopoietic stem progenitor cells (HSPCs, KSL-HSPCs). In this study, we investigate function of S1P₁ receptors in the regulation of HSPC mobilization in animals. Treatment with SEW2871, a specific agonist of S1P₁, had no effect on KSL-HSPC mobilization. In addition, mice pretreated with SEW2871 followed by AMD3100, a well-known activator of KSL-HSPC mobilization by antagonizing the stromal-derived factor-1 (SDF-1)/C-X-C chemokine receptor type 4 (CXCR4) signaling axis, did not enhance the AMD3100-induced KSL-HSPC mobilization. In contrast, pretreatment of (R)-3-amino-4-(3-hexylphenylamino)-4-oxobutyl phosphonic acid (W146), a selective antagonist of S1P₁, significantly augments AMD3100-induced KSL-HSPC mobilization into peripheral blood. The inactive enantiomer W140 was incapable of enhancing the AMD3100-induced KSL-HSPC mobilization. Moreover, treatment with selective antagonists for S1P₂ and S1P₃ had no effects on AMD3100-mediated KSL-HSPC mobilization. Collectively, our data suggest that S1P/S1P₁ signaling regulates the SDF-1/CXCR4-mediated retention of KSL-HSPCs in bone marrow microenvironment.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 4","pages":"197-203"},"PeriodicalIF":0.0,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4221244/pdf/nihms527920.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32802796","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":"An Ubiquitin-like Motif in ASK1 Mediates its Association with and Inhibition of the Proteasome.","authors":"Jeffrey R Schneider,&nbsp;James P Lodolce,&nbsp;David L Boone","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Linear polyubiquitin is processed at LRLRGG sequences by deubiquitinating enzymes to make free monomeric ubiquitin. This LRLRGG ubiquitin-like motif is found in a limited number of mammalian non-ubiquitin proteins, including the MAP3K Apoptosis Signal-Regulating Kinase-1 (ASK1), which activates MAPK signaling pathways. The c-terminus of ASK1 binds to the 19S cap of the proteasome allowing ASK1 to phosphorylate and inhibit proteasomal activity. We investigated whether the ubiquitin-like sequence in the c-terminus of ASK1 mediates its association with and inhibition of the proteasome. To test this we generated ASK1 with substitutions or deletions in this ubiquitin-like domain and examined the activation of cellular signaling and the association of ASK1 with the 19S cap of the proteasome. We show that ASK1 mutants have reduced association with the 19S cap of the proteasome, reduced capacity to inhibit the proteasome, and diminished ability to inhibit TNF-induced NF-κB activation. Mutant forms of ASK1 also had reduced capacity to activate JNK signaling, suggesting that the ubiquitin-like motif in ASK1 is also important for coordinating the balance between JNK and NF-κB signaling. Together these results demonstrate that the ubiquitin-like sequence of ASK1 is important for binding to and inhibition of the proteasome, and for the coordinated activation of cellular NF-κB and JNK signaling.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 3","pages":"161-167"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3839862/pdf/nihms509346.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31911628","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":"Autophagy: An Integral Component of the Mammalian Stress Response.","authors":"Stefan W Ryter,&nbsp;Augustine M K Choi","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Mammalian cells and tissues respond to chemical and physical stress by inducing adaptive or protective mechanisms that prolong survival. Among these, the major stress inducible proteins (heat shock proteins, glucose regulated proteins, heme oxygenase-1) provide cellular protection through protein chaperone and/or anti-oxidative and anti-inflammatory functions. In recent years it has become clear that autophagy, a genetically-programmed and evolutionarily-conserved cellular process represents another adaptive response to cellular stress. During autophagy cytosolic material, including organelles, proteins, and foreign pathogens, are sequestered into membrane-bound vesicles termed autophagosomes, and then delivered to the lysosome for degradation. Through recycling of cellular biochemicals, autophagy provides a mechanism for adaptation to starvation. Recent research has uncovered selective autophagic pathways that target distinct cargoes to autophagosomes, including mechanisms for the clearance of aggregated protein, and for the removal of dysfunctional mitochondria (mitophagy). Autophagy can be induced by multiple forms of chemical and physical stress, including endoplasmic reticulum stress and oxidative stress, and plays an integral role in the mammalian stress response. Understanding of the interaction and co-regulation of autophagy with other stress-inducible systems will be useful in the design and implementation of therapeutics targeting this pathway.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 3","pages":"176-188"},"PeriodicalIF":0.0,"publicationDate":"2013-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865984/pdf/nihms516986.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31971925","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":"Rapamycin Modulates Markers of Mitochondrial Biogenesis and Fatty Acid Oxidation in the Adipose Tissue of db/db Mice.","authors":"Sathyaseelan S Deepa,&nbsp;Michael E Walsh,&nbsp;Ryan T Hamilton,&nbsp;Daniel Pulliam,&nbsp;Yun Shi,&nbsp;Shauna Hill,&nbsp;Yan Li,&nbsp;Holly Van Remmen","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Excess nutrient uptake leads to obesity, insulin resistance, and type 2 diabetes. Mammalian target of the rapamycin (mTOR), a major component of the nutrient-sensing pathway also regulates mitochondrial oxidative function. Rapamycin, a pharmacological inhibitor of mTOR, causes glucose intolerance and inhibits mitochondrial oxidative function. While a number of studies have focused on the effect of rapamycin on control wild-type mice, ours is the first to study the effect of rapamycin on mitochondrial gene expression and insulin sensitivity in the db/db mouse, a model of diabetic dyslipidemia. Female db/+ and db/db mice were fed <i>ad libitum</i> a rapamycin-containing diet or a control diet for 6 months, starting at two months of age. Body weight, fat mass, lean mass and food intake were measured monthly. Effect of rapamycin or control diet on markers of adipogenesis, fatty acid oxidation and mitochondrial biogenesis in the gonadal white adipose tissue (WAT) as well as different serum parameters were assessed. Whole body insulin sensitivity was measured by insulin tolerance test. Rapamycin feeding to db/db mice decreased body weight (58%) and fat mass (33%), elevated markers of fatty acid oxidation and mitochondrial biogenesis in WAT, reduced circulating non-esterified free fatty acids (NEFA), elevated circulating adiponectin and improved insulin sensitivity, compared to control diet fed db/db mice. These data demonstrate that rapamycin exhibits an anti-obesity effect and improves whole body insulin sensitivity in db/db mice and suggest an unexpected effect of simultaneous inhibition mTOR and leptin signaling in mice.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 2","pages":"114-123"},"PeriodicalIF":0.0,"publicationDate":"2013-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3760510/pdf/nihms-505765.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31711355","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":"Rapamycin, Autophagy, and Alzheimer's Disease.","authors":"Zhiyou Cai,&nbsp;Liang-Jun Yan","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive impairment and multiple pathological lesions. At the molecular level, AD is characterized by overt amyloid β (Aβ) production and tau hyper-phosphorylation. Hence, pharmacological agents that can attenuate Aβ accumulation and tau hyper-phosphorylation have potential promise for treatment of AD. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), is believed to be one of such pharmacological agents. It is neuroprotective in neurodegenerative diseases and its primary action is thought to be via enhancement of autophagy, a biological process that not only facilitates the clearance of mutant proteins but also significantly reduces the build-up of toxic protein aggregates such as Aβ. Since rapamycin enhancement of autophagy has been associated with abrogation of AD pathological processes such as clearance of Aβ and neurofibrillary tangles (NTFs) as well as reduction of tau hyper-phosphorylation and improvement of cognition, rapamycin is emerging as a potential therapeutic compound for AD.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 2","pages":"84-90"},"PeriodicalIF":0.0,"publicationDate":"2013-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3697866/pdf/nihms475926.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31200399","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":"The Mediator Complex and Lipid Metabolism.","authors":"Yi Zhang,&nbsp;Xiaoli,&nbsp;Xiaoping Zhao,&nbsp;Fajun Yang","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The precise control of gene expression is essential for all biological processes. In addition to DNA-binding transcription factors, numerous transcription cofactors contribute another layer of regulation of gene transcription in eukaryotic cells. One of such transcription cofactors is the highly conserved Mediator complex, which has multiple subunits and is involved in various biological processes through directly interacting with relevant transcription factors. Although the current understanding on the biological functions of Mediator remains incomplete, research in the past decade has revealed an important role of Mediator in regulating lipid metabolism. Such function of Mediator is dependent on specific transcription factors, including peroxisome proliferator-activated receptor-gamma (PPARγ) and sterol regulatory element-binding proteins (SREBPs), which represent the master regulators of lipid metabolism. The medical significance of these findings is apparent, as aberrant lipid metabolism is intimately linked to major human diseases, such as type 2 diabetes and cardiovascular disease. Here, we briefly review the functions and molecular mechanisms of Mediator in regulation of lipid metabolism.</p>","PeriodicalId":89797,"journal":{"name":"Journal of biochemical and pharmacological research","volume":"1 1","pages":"51-55"},"PeriodicalIF":0.0,"publicationDate":"2013-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3686121/pdf/nihms465939.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31529625","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}