Nanoparticle-mediated intracellular lipid accumulation during C2C12 cell differentiation

In this report, we sought to elucidate whether multiwall carbon nanotubes are involved in the modulation of the proliferation and differentiation of the skeletal muscle cell line C2C12. Skeletal muscle is a major mass peripheral tissue that accounts for 40% of total body weight and 50% of energy consumption. We focused on the differentiation pathway of myoblasts after exposure to a vapor-grown carbon fiber, HTT2800, which is one of the most highly purified carbon nanotubes. This treatment leads in parallel to the expression of a typical adipose differentiation program. We found that HTT2800 stimulated intracellular lipid accumulation in C2C12 cells. We have also shown by quantified PCR analysis that the expression of adipose-related genes was markedly upregulated during HTT2800 exposure. Taken together, these results suggest that HTT2800 specifically converts the differentiation pathway of C2C12 myoblasts to that of adipoblast-like cells.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 406(4):558-563 (2011)journal articl

Cellular cytotoxic response induced by highly purified multi-wall carbon nanotube in human lung cells

Carbon nanotubes, a promising nanomaterial with unique characteristics, have applications in a variety of fields. The cytotoxic effects of carbon nanotubes are partially due to the induction of oxidative stress; however, the detailed mechanisms of nanotube cytotoxicity and their interaction with cells remain unclear. In this study, the authors focus on the acute toxicity of vapor-grown carbon fiber, HTT2800, which is one of the most highly purified multi-wall carbon nanotubes (MWCNT) by high-temperature thermal treatment. The authors exposed human bronchial epithelial cells (BEAS-2B) to HTT2800 and measured the cellular uptake, mitochondrial function, cellular LDH release, apoptotic signaling, reactive oxygen species (ROS) generation and pro-inflammatory cytokine release. The HTT2800-exposed cells showed cellular uptake of the carbon nanotube, increased cell death, enhanced DNA damage, and induced cytokine release. However, the exposed cells showed no obvious intracellular ROS generation. These cellular and molecular findings suggest that HTT2800 could cause a potentially adverse inflammatory response in BEAS-2B cells.ArticleMOLECULAR AND CELLULAR BIOCHEMISTRY. 352(1-2):57-63 (2011)journal articl

Valorization of solid tire wastes available in Bangladesh by thermal treatment

In this study available solid tire wastes in Bangladesh were characterized through proximate and ultimate analyses, gross calorific values and thermogravimetric analysis to investigate their suitability as feedstock for thermal recycling by pyrolysis technology. A new approach in heating system, fixedbed fire-tube heating pyrolysis reactor has been designed and fabricated for the recovery of liquid hydrocarbons from solid tire wastes. The tire wastes were pyrolysed in the internally heated fixed-bed fire-tube heating reactor and maximum liquid yield of 46-55 wt% of solid tire waste was obtained at a temperature of 475 oC, feed size 4 cm3, with a residence time of 5 s under N2 atmosphere. The liquid products were characterized by physical properties, elemental analysis, FT-IR, 1H-NMR, GC MS techniques and distillation. The results show that the liquid products are comparable to petroleum fuels whereas fractional distillations and desulphurization are essential to be used as alternative for diesel engine fuels

Cyclic phosphatidic acid induces G0/G1 arrest, inhibits Akt phosphorylation, and downregulates cyclin D1 expression in colorectal cancer cells

17 Dec 2014. [Epub ahead of print]Lysophosphatidic acid (LPA) and its analogs are well-known mitogens for various cell types. Many reports have confirmed that several types of cancer cell produce LPA to promote survival, growth and tumorigenesis. This indicates that the interface between the LPA signaling pathway and the cell cycle signaling system is critical to the control of cancer cell proliferation. However, our previous study indicated that cyclic phosphatidic acid (cPA), which is structurally similar to LPA, inhibits the proliferation and migration of colon cancer cells. It has been reported that cPA shows several biological activities not shown by LPA. However, understanding of the detailed molecular and cellular mechanism underlying the regulation of the cell cycle by cPA is still in its infancy. In this study, we investigated the effect of cPA treatment on human DLD-1 colon cancer cells by analyzing cell cycle dynamics, gene expression, and AKT phosphorylation. Our findings indicate that cPA inhibits cell cycle progression in DLD-1 colon cancer cells via the downregulation of cyclin D1 and the inhibition of AKT phosphorylation.ArticleCellular Molecular Biology Letters. (17 Dec 2014) doi:10.1038/leu.2014.239journal articl

Cyclic Phosphatidic Acid Inhibits Alkyl-Glycerophosphate-Induced Downregulation of Histone Deacetylase 2 Expression and Suppresses the Inflammatory Response in Human Coronary Artery Endothelial Cells

Activation of the endothelium by alkyl-glycerophosphate (AGP) has been implicated in the development of atherosclerosis. Our previous study suggested that cyclic phosphatidic acid (cPA) inhibits arterial wall remodeling in a rat model in vivo. However, the mechanisms through which specific target genes are regulated during this process remain unclear. Here, we examined whether cPA inhibited AGP-induced expression of class I histone deacetylases (HDACs, namely HDAC1, HDAC2, HDAC3, and HDAC8), which may affect subsequent transcriptional activity of target genes. Our experimental results showed that human coronary artery endothelial cells (HCAECs) expressed high levels of HDAC2 and low levels HDAC1, HDAC3, and HDAC8. Moreover, AGP treatment induced downregulation of HDAC2 expression in HCAECs. However, cotreatment with cPA inhibited this downregulation of HDAC2 expression. Interestingly, treatment with AGP increased the expression and secretion of endogenous interleukin (IL)-6 and IL-8; however, this effect was inhibited when HCAECs were cotreated with cPA or the synthetic peroxisome proliferator-activator receptor gamma (PPARγ) antagonist T0070907. Thus, our data suggested that cPA may have beneficial effects in inflammation-related cardiovascular disease by controlling HDAC2 regulation.ArticleInt. J. Med. Sci. 11(9):955-961 (2014)journal articl

The thermodynamic landscape of carbon redox biochemistry

Redox biochemistry plays a key role in the transduction of chemical energy in all living systems. Observed redox reactions in metabolic networks represent only a minuscule fraction of the space of all possible redox reactions. Here we ask what distinguishes observed, natural redox biochemistry from the space of all possible redox reactions between natural and non-natural compounds. We generate the set of all possible biochemical redox reactions involving linear chain molecules with a fixed numbers of carbon atoms. Using cheminformatics and quantum chemistry tools we analyze the physicochemical and thermodynamic properties of natural and non-natural compounds and reactions. We find that among all compounds, aldose sugars are the ones with the highest possible number of connections (reductions and oxidations) to other molecules. Natural metabolites are significantly enriched in carboxylic acid functional groups and depleted in carbonyls, and have significantly higher solubilities than non-natural compounds. Upon constructing a thermodynamic landscape for the full set of reactions as a function of pH and of steady-state redox cofactor potential, we find that, over this whole range of conditions, natural metabolites have significantly lower energies than the non-natural compounds. For the set of 4-carbon compounds, we generate a Pourbaix phase diagram to determine which metabolites are local energetic minima in the landscape as a function of pH and redox potential. Our results suggest that, across a set of conditions, succinate and butyrate are local minima and would thus tend to accumulate at equilibrium. Our work suggests that metabolic compounds could have been selected for thermodynamic stability, and yields insight into thermodynamic and design principles governing nature’s metabolic redox reactions.https://www.biorxiv.org/content/10.1101/245811v1Othe

The AGP-PPAR gamma axis promotes oxidative stress and diabetic endothelial cell dysfunction

Alkyl-glycerophosphate (AGP) accumulates in atherogenic oxidized-LDL and human atherosclerotic plaques and is a potent agonist of peroxisome-proliferator-activated receptor-gamma (PPAR gamma). Recent studies suggest a potential regulatory role for PPAR gamma in endothelial nitric oxide synthase (eNOS) expression/activation and nitrogen oxide (NO) generation in the vascular endothelium. Importantly, eNOS-induced NO and advanced glycation end-products (AGEs) are involved in blood-vessel damage, and diabetic patients exhibit high serum NO and AGE levels; however, the effect of AGP on NO- and AGE-mediated endothelium dysfunction remains unknown. Investigation of the AGP-specific effects on NO- and AGE-mediated dysfunction and the underlying molecular mechanisms revealed that AGP upregulated eNOS expression and NO production, and that eNOS silencing and gamma antagonism inhibited AGP-mediated eNOS upregulation and NO production. Moreover, AGP-PPAR gamma-axis-mediated NO production promoted the generation of reactive oxygen species and AGE formation. These results suggested that AGP plays a significant role in the initiation/progression of diabetes-related atherosclerosis through PPAR gamma activation. (C) 2018 Elsevier B.V. All rights reserved.ArticleMOLECULAR AND CELLULAR ENDOCRINOLOGY. 473:100-113 (2018)journal articl

Studies on highly strained three-membered ring compounds containing sulfur

Thesis--University of Tsukuba, D.Sc.(A), no. 293, 1985. 3. 2

Evaluation of MC3T3-E1 Cell Osteogenesis in Different Cell Culture Media

Many biomaterials have been evaluated using cultured cells. In particular, osteoblast-like cells are often used to evaluate the osteocompatibility, hard-tissue-regeneration, osteoconductive, and osteoinductive characteristics of biomaterials. However, the evaluation of biomaterial osteogenesis-inducing capacity using osteoblast-like cells is not standardized; instead, it is performed under laboratory-specific culture conditions with different culture media. However, the effect of different media conditions on bone formation has not been investigated. Here, we aimed to evaluate the osteogenesis of MC3T3-E1 cells, one of the most commonly used osteoblast-like cell lines for osteogenesis evaluation, and assayed cell proliferation, alkaline phosphatase activity, expression of osteoblast markers, and calcification under varying culture media conditions. Furthermore, the various media conditions were tested in uncoated plates and plates coated with collagen type I and poly-L-lysine, highly biocompatible molecules commonly used as pseudobiomaterials. We found that the type of base medium, the presence or absence of vitamin C, and the freshness of the medium may affect biomaterial regeneration. We posit that an in vitro model that recapitulates in vivo bone formation should be established before evaluating biomaterials.ArticleInternational Journal of Molecular Sciences. 22(14):7752 (2021)journal articl

Lysophosphatidic acid signaling regulates the KLF9-PPAR gamma axis in human induced pluripotent stem cell-derived neurons

Lysophosphatidic acid (LPA) is a lipid signaling molecule that plays several significant roles in the nervous system during development and injury. In this study, we differentiated human induced pluripotent stem cells (iPSCs) into neurons as an in vitro model to examine the specific effects of LPA. We demonstrated that LPA activates peroxisome proliferator-activated receptor gamma (PPAR gamma), a ligand-activated nuclear receptor, as well as its cognate receptor LPA(1) on human iPSC-derived neurons to enhance proliferation and neurite outgrowth. Furthermore, we found that the gene expression of Kruppel-like factor 9 (KLF9), a member of the large KLF transcription factor family, was induced by LPA treatment. Knockdown of KLF9 decreased proliferation and neurite outgrowth in vehicle- and LPA-treated IPSC-derived neurons compared to cells expressing KLF9. In conclusion, LPA plays dual roles as a ligand mediator through the activation of cell surface G-coupled protein receptors and as an intracellular second messenger through the activation of PPAR gamma. We discuss the contribution of the LPA(1)-PPAR(gamma)-KLF9 axis to neurite outgrowth and proliferation in human iPSC-derived neurons. (C) 2017 Elsevier Inc. All rights reserved.ArticleBIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS. 491(1):223-227 (2017)journal articl