Advances in Biological Chemistry最新文献

{"title":"Preservation Potentials of Essential Oils of <i>Ocimum basilicum</i> and <i>Ocimum gratissimum</i> from Two Agro-Ecological Zones on Freshwater Smoke-Dried <i>Oreochromis niloticus</i> Fish Sold in Some Local Markets in Cameroon","authors":"Tsi Celestine Angu, Pride Ndasi Ngwasiri, Lifoter Kenneth Navti, Diane Youmbi Yimta, Fonteh Florence Anyanwe Angaba","doi":"10.4236/abc.2023.135014","DOIUrl":"https://doi.org/10.4236/abc.2023.135014","url":null,"abstract":"Dried fish are susceptible to bacteria and fungi attack and are liable to chemical changes which cause losses in quality and reduction of shelf-life. It is important therefore to maintain the quality of fish because continuous consumption of contaminated fish and their products may predispose consumers to health hazards. Maintenance of high quality fish therefore calls for adequate and effective preservation techniques. The study examined the effectiveness of essential oils of Ocimum basilicum and Ocimum gratissimum from two Agro-ecological zones of Cameroon in limiting the microbial proliferation and preserving the quality of smoke-dried Oreochromis niloticus fish stored at 25˚C for two months. The plant materials were harvested from the Western Highlands and Monomodal Humid Forest agroecological zones of Cameroon. Extraction of the essential oil from the plants was done by hydro-distillation. The fish species (Oreochromis niloticus) used in this study was chosen based on a survey study on the most consumed species of freshwater smoke-dried fish in the Western Highlands and Monomodal Humid Forest Agro-ecological zones of Cameroon. Heterotrophic bacteria counts, fungi counts and Enterobacteriaceae counts were used to assess the level heterotrophic bacteria, fungi and Enterobacteriaceae respectively in the fish samples during storage and were done by culture techniques using total plate count agar, potato dextrose agar and violet red bile glucose agar respectively. Total volatile basic nitrogen, peroxide value, and thiobarbituric acid reactive substance assays were used as spoilage indices to assess the nutritional quality of the fish during storage. From the survey study, Oreochromis niloticus was the most consumed smoke-dried fish in the Western Highlands (35.45%) and Monomodal Humid Forest (34.55%) agroecological zones. All the EOs caused a significant reduction in the microbial loads, total volatile basic nitrogen, peroxide value, and thiobarbituric acid reactive substance of smoke-dried Oreochromis niloticus as storage progressed. However, the reduction in these values was more pronounced in samples treated with essential oils of O. gratissimum from the Western Highlands, with heterotrophic bacteria, fungi and Enterobacteriaceae counts being 5.89, 6.97 and 4.59 log10 cfu/g respectively at the end of the storage period. This was followed by essential oils of O. gratissimum from the Monomodal Humid Forest with heterotrophic bacteria, fungi and Enterobacteriaceae counts being 6.11, 7.79 and 4.86 log10 cfu/g respectively at the end of the storage period. Also, essential oils of O. gratissimum from the Western Highlands was more effective in preserving the fish quality as lowest total volatile basic nitrogen (12.29 mg/100g), peroxide value (2.79 mEq O2·Kg−1) and thiobabituric reactive substance (1.695 mg MDA/Kg) values were observed for fish samples treated with this extract at the end of the storage period. This was followed by essential oils of ","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"180 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135052607","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Mannich Bases of Benzimidazole Derivatives: An Antibacterial Study of Environmental Bacterial Strains","authors":"Evrard Ablo, Ouehi Dosso, Bakary Coulibaly, Kouassi Franscesco Adingra, Penayori Marie-Aimée Coulibaly, Armand Patrick Achi, Tchambaga Etienne Camara, Souleymane Coulibaly, Siomenan Coulibali","doi":"10.4236/abc.2023.135013","DOIUrl":"https://doi.org/10.4236/abc.2023.135013","url":null,"abstract":"A previous study was conducted on the synthesis and antibacterial evaluation of Mannich bases of 2-(thioalkyl)-1H-methylbenzimidazole derivatives. The results of this study showed that certain 2-(thioalkyl)-1H-methylbenzimidazole and 2-(thioalkyl)-methyl-1-(piperidin-1-ylmethyl)benzimidazole derivatives possess antibacterial activities against clinical strains, such as Escherichia coli, Klebsiella pneumonia (Gram-negative bacteria), Staphylococcus aureus and Pseudomonas aeruginosa (Gram-positive bacteria). Following these favorable results, we extended the antibacterial evaluation of this series of molecules to environmental strains. The aim of this study was to assess the impact of the methyl-piperidine group fixed at position-1 of this new series of benzimidazoles on the antibacterial activity of environmental strains. In addition, we first evaluated the antibacterial activity of four 2-(thioalkyl)methylbenzimidazole derivatives and then that of five 2-(thioalkyl)-methyl-1-(piperidin-1-ylmethyl) benzimidazole derivatives. This study allowed us to show that compounds 1d and 1e could inhibit bacterial growth in vitro of the Enterobacteria P1 strain with inhibition diameters of 17.3 ± 0.6 mm and 10 ± 0.0 mm, respectively. However, addition of methyl-piperidinyl in this series showed that five (5) of 2-(thioalkyl)-methyl-1-(piperidin-1-ylmethyl) benzimidazole derivatives had an inhibitory effect on the in vitro growth of bacterial strains used except on Enterobacteria P2 with inhibition diameters between 10.0 ± 0.8 mm and 27.9 ± 1.4 mm. The introduction of the methyl-piperidinyl group at the 1-position of 2-(thioalkyl)-1H-methylbenzimidazole derivatives greatly improved the antibacterial activity against environmental bacteria such as Escherichia coli A1, A2, A3, and A4 and two Enterobacteria P1.","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"60 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135006746","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Influence of Haptoglobin and Hemoglobin Phenotypic Polymorphisms on Sickle Cell Disease Morbidity","authors":"Hugues Ahiboh, Akissi Joelle Koffi, Aniéla Kanga, Philemond By, Fatoumata Koné, Hermance Kassi, Francisk Kouakou, Marie-Laure Hauhouot-Attoungbré, Duni Sawadogo","doi":"10.4236/abc.2023.135012","DOIUrl":"https://doi.org/10.4236/abc.2023.135012","url":null,"abstract":"Objectives: Sickle cell disease (SCD) has a varied clinical and biological expression depending on the hemoglobin phenotype: SSFA2, SFA2, SAFA2 and SC. Considering the antioxidant properties of the different haptoglobin phenotypes (Hp 1-1, Hp 2-1, Hp 2-2), it seemed relevant to know their influence on the morbidity of the different hemoglobin phenotype of SCD. Thus, the objective of this study was to identify associations between haptoglobin phenotype and morbidity of different SCD phenotypes. Methods: In a retrospective cross-sectional descriptive and analytical study, with a cohort of 170 black African carriers of hemoglobin S, in Ivory Coast, West Africa, hemoglobin and haptoglobin phenotypes were determined by electrophoretic methods. Results: The three major phenotypes of haptoglobin polymorphism were found in the SCD cohort: Hp 1-1 (24.1%), Hp 2-1 (56.5%), Hp 2-2 (19.4%). Vaso-occlusions were associated with haptoglobin phenotype Hp 1-1, (OR = 2.03; CI95% = [1.06 - 3.9]; p 2 (CI95% = [1.43 - 14.44]) and the probability of having the Hp 1-1 phenotype was lower (CI95% = [0.170 - 0.705]). Conclusions: Haptoglobin phenotype was associated to morbidity-adjusted hemoglobin phenotype. The study revealed a greater probability of a worse morbidity when the hemoglobin phenotype is homozygous. Unexpectedly, the worse morbidity is associated to Hp 1-1 haptoglobin phenotype, the most powerful antioxidant within the different haptoglobin phenotypes. Associations found were not systematic and need further studies to enlighten the determinism of SCD morbidity.","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"16 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136208178","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flavonoids Reduce Lipid Peroxides and Increase Glutathione Levels in Pooled Human Liver Microsomes (HLMs).","authors":"William Yaw Boadi, Camille Stevenson, Dontrez Johnson, Mohamed Adel Mohamed","doi":"10.4236/abc.2021.116019","DOIUrl":"10.4236/abc.2021.116019","url":null,"abstract":"<p><p>The effects of each of the flavonoids; genistein (G), quercetin (Q) and kaempferol (K) at several doses on lipid peroxides (LP) and reduced glutathione (GSH) in pooled human liver microsomes (HLMs) were investigated following the oxidative damage for 4, 6, 18 and 24 hr. HLMs (1 mg/ml) were exposed to each of the above flavonoids at 0, 5, 10, 15, 20 or 25 μM and incubated for the respective times as previously stated. Our hypothesis was that HLMs exposed to the flavonoids for the respective exposure times can decrease LP and increase GSH in HLMs to better cope with the oxidative stress. The results of our studies indicate that each of the flavonoids significantly (p < 0.01) decreased LP compared to their respective controls. The highest decrease in LP was observed for K followed by Q and G. Significant increases (p < 0.01) in GSH were observed for the flavonoid doses tested with the highest levels observed for Q for the 24-hr. incubation. The findings suggest that the flavonoids modulate oxidative stress in HLMs by decreasing LP and such decreases in LPs may be due to the increasing and or the replenished levels of GSH in the said cells to better cope with the oxidative stress.</p>","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"11 6","pages":"283-295"},"PeriodicalIF":0.0,"publicationDate":"2021-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9634994/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10700753","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":"Evaluation of Silicon Phthalocyanine 4 Photodynamic Therapy Against Human Cervical Cancer Cells In Vitro and in Mice.","authors":"Jill A Gadzinski,&nbsp;Jianxia Guo,&nbsp;Brian J Philips,&nbsp;Per Basse,&nbsp;Ethan K Craig,&nbsp;Lisa Bailey,&nbsp;John T Comerci,&nbsp;Julie L Eiseman","doi":"10.4236/abc.2016.66017","DOIUrl":"https://doi.org/10.4236/abc.2016.66017","url":null,"abstract":"<p><strong>Background: </strong>Cervical cancer is the second most common cancer in women worldwide [1]. Photodynamic therapy has been used for cervical intraepithelial neoplasia with good responses, but few studies have used newer phototherapeutics. We evaluated the effectiveness of photodynamic therapy using Pc 4 in vitro and in vivo against human cervical cancer cells.</p><p><strong>Methods: </strong>CaSki and ME-180 cancer cells were grown as monolayers and spheroids. Cell growth and cytotoxicity were measured using a methylthiazol tetrazolium assay. Pc 4 cellular uptake and intracellular distrubtion were determined. For in vitro Pc 4 photodynamic therapy cells were irradiated at 667nm at a fluence of 2.5 J/cm² at 48 h. SCID mice were implanted with CaSki and ME-180 cells both subcutaneously and intracervically. Forty-eight h after Pc 4 photodynamic therapy was administered at 75 and 150 J/cm².</p><p><strong>Results: </strong>The IC₅₀s for Pc 4 and Pc 4 photodynamic therapy for CaSki and ME-180 cells as monolayers were, 7.6μM and 0.016μM and >10μM and 0.026μM; as spheroids, IC₅₀s of Pc 4 photodynamic therapy were, 0.26μM and 0.01μM. Pc 4 was taken up within cells and widely distributed in tumors and tissues. Intracervical photodynamic therapy resulted in tumor death, however mice died due to gastrointestinal toxicity. Photodynamic therapy resulted in subcutaneous tumor death and growth delay.</p><p><strong>Conclusions: </strong>Pc 4 photodynamic therapy caused death within cervical cancer cells and xenografts, supporting development of Pc 4 photodynamic therapy for treatment of cervical cancer. Support: P30-CA47904, CTSI BaCCoR Pilot Program.</p>","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"6 6","pages":"193-215"},"PeriodicalIF":0.0,"publicationDate":"2016-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5589197/pdf/nihms898532.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35393189","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":"Rad7 E3 Ubiquitin Ligase Attenuates Polyubiquitylation of Rpn10 and Dsk2 Following DNA Damage in <i>Saccharomyces cerevisiae</i>.","authors":"Joseph M Benoun,&nbsp;Danielle Lalimar-Cortez,&nbsp;Analila Valencia,&nbsp;Adriana Granda,&nbsp;Destaye M Moore,&nbsp;Eric P Kelson,&nbsp;Paula L Fischhaber","doi":"10.4236/abc.2015.57021","DOIUrl":"https://doi.org/10.4236/abc.2015.57021","url":null,"abstract":"<p><p>During Nucleotide Excision Repair (NER) in the yeast <i>S. cerevisiae</i>, ubiquitylation of Rad4 is carried out by the E3 ubiquitin ligase that includes Rad7-Elc1-Cul3 and is critical to optimal NER. Rad7 E3 activity targets Rad4 for degradation by the proteaseome but, in principle, could also trigger other DNA damage responses. We observed increased nuclear ubiquitin foci (Ub-RFP) formation in <i>S. cerevisiae</i> containing a Rad7 E3 ligase mutant (<i>rad7SOCS</i>) in response to DNA damage by benzo[a]pyrenediolepoxide (BPDE) in dividing cells. Immunoblots reveal that ubiquitin conjugates of Rpn10 and Dsk2 accumulate in greater abundance in <i>rad7SOCS</i> compared to <i>RAD7</i> in dividing cells in response to BPDE which makes Rpn10 and Dsk2 candidates for being the ubiquitylated species observed in our microscopy experiments. Microscopy analysis with strains containing Dsk2-GFP shows that Dsk2-GFP and Dsk2-GFP/Ub-RFP colocalized in nuclear foci form to an increased extent in a <i>rad7SOCS</i> mutant background in dividing cells than in a <i>RAD7</i> wild-type strain. Further, Dsk2-GFP in the <i>rad7SOCS</i> strain formed more foci at the plasma membrane following BPDE treatment in dividing cells relative to strains containing <i>RAD7</i> or a <i>rad7Δ</i> deletion mutant. In response to a different agent, UV irradiation, levels of ubiquitylated proteins were increased in <i>rad7SOCS</i> relative to <i>RAD7</i>, and the proteasomal deubiquitylase subunit, Rpn11 was even monoubiquitylated in the absence of damaging agents. Together these data show that Rad7 E3 activity attenuates ubiquitylation of proteins regulating the shuttling of polyubiquitylated proteins to the proteasome (Dsk2 and Rpn10) and removal of ubiquitin chains just prior to degradation (Rpn11). Since Rad7 E3 ligase activity has been shown to increase ubiquitylation of its target proteins, yet our results show increased ubiquitylation in the absence of Rad7 E3, we suggest that Rad7 E3 action regulates ubiquitin ligase and deubiquitylase (DUB) activities that act on Rpn10, Dsk2 and Rpn11.</p>","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"5 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2015-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4832922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34316081","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":"Permeation of roxarsone and its metabolites increases caco-2 cell proliferation.","authors":"Gladys S Bayse,&nbsp;Latanya P Hammonds-Odie,&nbsp;Kimberly M Jackson,&nbsp;Deidre K Tucker,&nbsp;Ward G Kirlin","doi":"10.4236/abc.2013.34041","DOIUrl":"https://doi.org/10.4236/abc.2013.34041","url":null,"abstract":"<p><p>The benzenearsonate, Roxarsone, has been used since 1944 as an antimicrobial, growth-promoting poultry feed additive. USGS and EPA report that Roxarsone (4-hydroxy-3-nitrobenzenearsonate) and metabolites, including AHBA (3-amino-4-hydroxybenzenearsonate), contaminate waterways at greater than 1100 tons annually. To assess human impact of these organic arsenic water contaminants, it was important to study their potential absorption. The human adenocarcinoma cell line, Caco-2, is a model for intestinal absorption. We found proliferative effects on Caco-2 cells at micromolar levels of these compounds, as monitored by [³H]-thymidine incorporation into DNA. Flow cytometry cell cycle analysis confirmed accumulation in S phase from 21% (control) to 36% (24 hour exposure to 10 μM AHBA). Confluent Caco-2 cells grown on collagen-coated Transwell plates were dosed on the apical side. After exposure, media from apical and basolateral sides were collected separately. Following removal of FBS by 30K centrifugal filtration, the benzenearsonates in the collected media were analyzed by HPLC. Analyses were at wavelengths in the ultraviolet/visible range where the absorbance values were linear with respect to concentration. Concentrations were calculated by comparison with analytically-prepared commercial standards. Results from cells dosed at 10 μM for 24 hours with AHBA, Roxarsone, or Acetarsone indicated 6% - 29% permeation occurring from apical to basolateral side, modeling absorption across intestinal epithelium to the circulatory system. Benzenearsonate feed additives are frequently applied in combination with antibiotics, raising additional health concerns. We conclude that micromolar levels of these benzenearsonates are adequate to stimulate Caco-2 cell proliferation.</p>","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"3 4","pages":"389-396"},"PeriodicalIF":0.0,"publicationDate":"2013-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4306191/pdf/nihms654504.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33337201","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":"Rad51 ATP binding but not hydrolysis is required to recruit Rad10 in synthesis-dependent strand annealing sites in <i>S. cerevisiae.</i>","authors":"Justin Karlin,&nbsp;Paula L Fischhaber","doi":"10.4236/abc.2013.33033","DOIUrl":"https://doi.org/10.4236/abc.2013.33033","url":null,"abstract":"<p><p>Several modes of eukaryotic of DNA double strand break repair (DSBR) depend on synapsis of complementary DNA. The Rad51 ATPase, the <i>S. cerevisiae</i> homolog of <i>E. coli</i> RecA, plays a key role in this process by catalyzing homology searching and strand exchange between an invading DNA strand and a repair template (e.g. sister chromatid or homologous chromosome). Synthesis dependent strand annealing (SDSA), a mode of DSBR, requires Rad51. Another repair enzyme, the Rad1-Rad10 endonuclease, acts in the final stages of SDSA, hydrolyzing 3' overhanging single-stranded DNA. Here we show <i>in vivo</i> by fluorescence microscopy that the ATP binding function of yeast Rad51 is required to recruit Rad10 SDSA sites indicating that Rad51 pre-synaptic filament formation must occur prior to the recruitment of Rad1-Rad10. Our data also show that Rad51 ATPase activity, an important step in Rad51 filament disassembly, is not absolutely required in order to recruit Rad1-Rad10 to DSB sites.</p>","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"3 3","pages":"295-303"},"PeriodicalIF":0.0,"publicationDate":"2013-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4205939/pdf/nihms491653.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32772528","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":"Activation of peroxisome proliferator activated receptor-gamma results in an atheroprotective apolipoprotein profile in HepG2 cells.","authors":"Diala F Dahabreh,&nbsp;Jheem D Medh","doi":"10.4236/abc.2012.23026","DOIUrl":"https://doi.org/10.4236/abc.2012.23026","url":null,"abstract":"<p><strong>Background: </strong>Insulin resistance is linked to dyslipidemia, characterized by a decrease in high density lipoproteins and an increase in low density lipoproteins. Thiazolidinediones (TZDs) are insulin-sensitizing agents used to improve glycemic control in patients with type 2 diabetes. Recently, the safety of certain TZD regimens has been questioned because of associated adverse effects on the plasma lipid profile. We examined the effect of a TZD, Ciglitazone, on apolipoprotein synthesis and secretion in human liver HepG2 cells.</p><p><strong>Methods and results: </strong>The effect of Ciglitazone treatment on apolipoprotein synthesis was addressed at the level of transcription, translation and secretion. RT-PCR showed that Ciglitazone increased the transcription of apoE and apoAI but reduced the levels of apoCI and apoB mRNA. Western blot analysis showed an increase in apoAI and apoE secreted in the cell culture media, whereas the amounts of apoB100 and apoCI were reduced. To confirm that Ciglitazone regulates apolipoprotein translation, its effect on <i>de novo</i> protein synthesis was evaluated by metabolic labeling with [³⁵S]-methionine/cysteine, and a similar pattern of regulation was observed. The change in apolipoprotein levels was not secondary to cholesterol biosynthesis or clearance, since Ciglitazone did not regulate the transcription of HMGCoA reductase, or the LDL receptor. However, mRNA levels for both PPAR-γ and LXRα were induced, suggesting a role for either or both receptors in modulating the hepatic apolipoprotein profile. The involvement of these nuclear receptor transcription factors was confirmed since direct activation of these receptors by endogenous PPAR-γ ligand, 15d-prostaglandin J₂, or LXRα ligand, 22(R)hydroxycholesterol, similarly upregulated apoAI and apoE, but down-regulated apoB100 protein synthesis.</p><p><strong>Conclusion: </strong>Our results suggest that Ciglitazone treatment results in an atheroprotective lipoprotein profile in liver cells. Thus, while the adipose and muscle tissues may be primary targets in TZD-mediated glucose homeostasis, liver PPAR-γ contributes significantly to the regulation of plasma lipoprotein profile.</p>","PeriodicalId":7245,"journal":{"name":"Advances in Biological Chemistry","volume":"2 3","pages":"218-225"},"PeriodicalIF":0.0,"publicationDate":"2012-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3632096/pdf/nihms-446659.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"31476332","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}