Cell Structure and Function (Cell Struct Funct)

Publisher: Nihon Saibō Seibutsu Gakkai

Journal description

Journal of the Japan Society of Cell Biology

Current impact factor: 2.35

Impact Factor Rankings

2015 Impact Factor Available summer 2015
2013 / 2014 Impact Factor 2.35
2012 Impact Factor 1.647
2011 Impact Factor 2.292
2010 Impact Factor 3.265
2009 Impact Factor 2.568
2008 Impact Factor 2.152
2006 Impact Factor 2.143
2005 Impact Factor 3.354
2004 Impact Factor 2.932
2003 Impact Factor 1.664
2002 Impact Factor 0.872
2001 Impact Factor 1.26
2000 Impact Factor 0.96
1999 Impact Factor 1.322
1998 Impact Factor 1.453
1997 Impact Factor 0.942
1996 Impact Factor 0.772
1995 Impact Factor 0.98
1994 Impact Factor 0.898
1993 Impact Factor 1.186
1992 Impact Factor 1.351

Impact factor over time

Impact factor
Year

Additional details

5-year impact 2.38
Cited half-life 0.00
Immediacy index 0.59
Eigenfactor 0.00
Article influence 1.03
Website Cell Structure and Function website
Other titles Cell structure and function (Online)
ISSN 1347-3700
OCLC 53814898
Material type Document, Periodical, Internet resource
Document type Internet Resource, Computer File, Journal / Magazine / Newspaper

Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Numerous types of cancer cells migrate into extracellular tissues. This phenomenon is termed invasion, and is associated with poor prognosis in cancer patients. In this study, we demonstrated that filamin B (FLNb), an actin-binding protein, is highly expressed in cancer cell lines that exhibit high invasiveness, with a spindle morphology, into 3D collagen matrices. In addition, we determined that knockdown of FLNb in invasive cancer cells converts cell morphology from spindle-shaped, which is associated with high invasiveness, to round-shaped with low invasiveness. Furthermore, di-phosphorylation of myosin regulatory light chain (MRLC) and phosphorylation of focal adhesion kinase (FAK) are inhibited in FLNb-knockdown cancer cells. These results suggest that FLNb enhances invasion of cancer cells through phosphorylation of MRLC and FAK. Therefore, FLNb may be a new therapeutic target for invasive cancers.
    Cell Structure and Function 04/2015; DOI:10.1247/csf.15001
  • [Show abstract] [Hide abstract]
    ABSTRACT: Checkpoint kinase 1 (Chk1) is a conserved protein kinase central to the cell-cycle checkpoint during DNA damage response (DDR). Until recently, ATR, a protein kinase activated in response to DNA damage or stalled replication, has been considered as the sole regulator of Chk1. Recent progress, however, has led to the identification of additional protein kinases involved in Chk1 phosphorylation, affecting the subcellular localization and binding partners of Chk1. In fact, spatio-temporal regulation of Chk1 is of critical importance not only in the DDR but also in normal cell-cycle progression. In due course, many potent inhibitors targeted to Chk1 have been developed as anticancer agents and some of these inhibitors are currently in clinical trials. In this review, we summarize the current knowledge of Chk1 regulation by phosphorylation.
    Cell Structure and Function 02/2015; 40(1):43-50. DOI:10.1247/csf.14017
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although most cell lines undergo mitotic arrest after prolonged exposure to microtubule inhibitors, some cells subsequently exit this state and become tetraploid. Among these cells, limited numbers of rodent cells are known to undergo multinucleation to generate multiple small independent nuclei, or micronuclei by prolonged colcemid treatment. Micronuclei are thought to be formed when cells shift to a pseudo G1 phase, during which the onset of chromosomal decondensation allows individual chromosomes distributed throughout the cell to serve as sites for the reassembly of nuclear membranes. To better define this process, we used long-term live cell imaging to observe micronucleation induced in mouse A9 cells by treating with the microtubule inhibitor colcemid. Our observations confirm that nuclear envelope formation occurs when mitotic-arrested cells shift to a pseudo G1 phase and adopt a tetraploid state, accompanied by chromosome decondensation. Unexpectedly, only a small number of cells containing large micronuclei were formed. We found that tetraploid micronucleated cells proceeded through an additional cell cycle, shifting to a pseudo G1 phase and forming octoploid micronucleated cells that were smaller and more numerous compared with the tetraploid micronucleated cells. Our data suggest that micronucleation occur when cells shift from mitotic arrest to a pseudo G1 phase, and demonstrate that, rather than being a single event, micronucleation is an inducible recurrent process that leads to the formation of progressively smaller and more numerous micronuclei.
    Cell Structure and Function 01/2015; DOI:10.1247/csf.14005
  • [Show abstract] [Hide abstract]
    ABSTRACT: The NACK kinesins (NACK1, NACK2 in tobacco and AtNACK1/HINKEL, AtNACK2/STUD/TETRASPORE in Arabidopsis), members of a plant-specific kinesin-7 family, are required for cytokinesis. Previous studies using tobacco and Arabidopsis cells showed that NACK1 and AtNACK1 at the phragmoplast midzone activate the MAP kinase cascade during the late M phase, which is critical for the cell plate formation. However, the loss-of-function phenotype has not been investigated in details in living cells and the molecular activity of this kinesin remains to be determined. Here, we report the mitotic roles and activity of the NACK kinesins in the moss Physcomitrella patens. When we simultaneously knocked down three PpNACKs by RNA-interference (RNAi) in protonemal cells, we observed a cytokinesis failure following a defect in phragmoplast expansion. In addition, misaligned chromosomes were frequently detected in the pre-anaphase spindle and the anaphase onset was significantly delayed, indicating that PpNACK also plays a role in pre-anaphase. Consistent with the appearance of early and late mitotic phenotypes, endogenous PpNACK was localised to the interpolar microtubule (MT) overlap from prometaphase through telophase. In vitro MT gliding assay and single motor motility assay showed that PpNACK-b is a processive, plus-end-directed motor, suggesting that PpNACK is capable of transporting cargoes along the spindle/phragmoplast MT. Our study using Physcomitrella patens demonstrated that PpNACK is an active motor protein and identified unexpected and conserved roles of PpNACK during the mitosis of P. patens.
    Cell Structure and Function 01/2015; 40(1):31-41. DOI:10.1247/csf.14016
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Golgi stress response is a mechanism by which, under conditions of insufficient Golgi function (Golgi stress), the transcription of Golgi-related genes is upregulated through an enhancer, the Golgi apparatus stress response element (GASE), in order to maintain homeostasis in the Golgi. The molecular mechanisms associated with GASE remain to be clarified. Here, we identified TFE3 as a GASE-binding transcription factor. TFE3 was phosphorylated and retained in the cytoplasm in normal growth conditions, whereas it was dephosphorylated, translocated to the nucleus and activated Golgi-related genes through GASE under conditions of Golgi stress, e.g. in response to inhibition of oligosaccharide processing in the Golgi apparatus. From these observations, we concluded that the TFE3-GASE pathway is one of the regulatory pathways of the mammalian Golgi stress response, which regulates the expression of glycosylation-related proteins in response to insufficiency of glycosylation in the Golgi apparatus.
    Cell Structure and Function 11/2014; DOI:10.1247/csf.14015
  • [Show abstract] [Hide abstract]
    ABSTRACT: Protein kinase A (PKA) is a serine/threonine kinase whose activity depends on the levels of cyclic AMP (cAMP). PKA plays essential roles in numerous cell types such as myocytes and neurons. Numerous substrate screens have been attempted to clarify the entire scope of the PKA signaling cascade, but it is still underway. Here, we performed a comprehensive screen that consisted of immunoprecipitation and mass spectrometry, with a focus on the identification of PKA substrates. The lysate of HeLa cells treated with Forskolin (FSK)/ 3-isobutyl methyl xanthine (IBMX) and/or H-89 was subjected to immunoprecipitation using anti-phospho-PKA substrate antibody. The identity of the phosophoproteins and phosphorylation sites in the precipitants was determined using liquid chromatography tandem mass spectrometry (LC/MS/MS). We obtained 112 proteins as candidate substrates and 65 candidate sites overall. Among the candidate substrates, Rho-kinase/ROCK2 was confirmed to be a novel substrate of PKA both in vitro and in vivo. In addition to Rho-kinase, we found more than a hundred of novel candidate substrates of PKA using this screen, and these discoveries provide us with new insights into PKA signaling.
    Cell Structure and Function 11/2014; 40(1). DOI:10.1247/csf.14014
  • [Show abstract] [Hide abstract]
    ABSTRACT: Here we describe the design and synthesis of a bifunctional two-photon fluorescence probe, N,N'-dimethyl-4,4'-(biphenyl-2,1-ethenediyl)dipyridinium hexafluorophosphate (BP6). HeLa, Hek293, and Paramecium caudatum cells were stained with BP6. BP6 accumulated on the mitochondria of all three cell types when the mitochondrial membrane potential was high. As the mitochondrial membrane potential decreased following the addition of carbonyl cyanide m-chlorophenyl hydrazine, BP6 moved from the mitochondria to the nucleus in a reversible manner, depending on the mitochondrial membrane potential status. The maximum value of the two-photon absorption cross-section of BP6 is 250 GM (1 GM = 1 × 10(-50) cm(4) s molecules(-1) photon(-1)). This value is 3 and 30 times larger, respectively, than that of the conventional mitochondria selective probes, rhodamine 123 and green fluorescence protein. These results suggest that BP6 should be useful for monitoring mitochondrial membrane potential by two-photon excitation.
    Cell Structure and Function 10/2014; DOI:10.1247/csf.14006
  • [Show abstract] [Hide abstract]
    ABSTRACT: Stem cells routinely maintain the main epidermal components, i.e. the interfollicular epidermis, hair follicles, and sweat glands. Human sweat glands present throughout the body are glandular exocrine organs that mainly play a role in thermoregulation by sweating. Emerging evidence points to the presence of stem cells in sweat glands, but it remains unclear whether such stem cells exist in human sweat glands. Here, we attempted to gather evidence for stem cells in human sweat glands, which would be characterized by self-renewal ability and multipotency. First, we explored human sweat gland cells for expression of stem cell markers. CD29 and Notch, epidermal stem cell markers, were found to reside among α-smooth muscle actin-positive myoepithelial cells in human sweat glands. Next, sweat gland myoepithelial cells were isolated from human skin as a CD29(hi)CD49f(hi) subpopulation. The myoepithelial cell-enriched CD29(hi)CD49f(hi) subpopulation possessed the ability to differentiate into sweat gland luminal cells in sphere-forming assays. Furthermore, CD29(hi)CD49f(hi) subpopulation-derived sphere-forming cells exhibited long-term proliferative potential upon multiple passaging, indicating that the CD29(hi)CD49f(hi) myoepithelial subpopulation includes stem cells with self-renewal ability. These findings provide evidence that human sweat gland myoepithelial cells contain stem cells that possess both self-renewal ability and multipotency to differentiate into sweat glands.
    Cell Structure and Function 09/2014; DOI:10.1247/csf.14009
  • [Show abstract] [Hide abstract]
    ABSTRACT: The transcription of ribosomal RNA genes (rDNA) is a rate-limiting step in ribosome biogenesis and changes profoundly in response to environmental conditions. Recently we reported that JmjC demethylase KDM2A reduces rDNA transcription on starvation, with accompanying demethylation of dimethylated Lys 36 of histone H3 (H3K36me2) in rDNA promoter. Here, we characterized the functions of two domains of KDM2A, JmjC and CxxC-ZF domains. After knockdown of endogenous KDM2A, KDM2A was exogenously expressed. The exogenous wild-type KDM2A demethylated H3K36me2 in the rDNA promoter on starvation and reduced rDNA transcription as endogenous KDM2A. The exogenous KDM2A with a mutation in the JmjC domain lost the demethylase activity and did not reduce rDNA transcription on starvation, showing that the demethylase activity of KDM2A itself is required for the control of rDNA transcription. The exogenous KDM2A with a mutation in the CxxC-ZF domain retained the demethylase activity but did not reduce rDNA transcription on starvation. It was found that the CxxC-ZF domain of KDM2A bound to the rDNA promoter with unmethylated CpG dinucleotides in vitro and in vivo. The exogenous KDM2A with the mutation in the CxxC-ZF domain failed to reduce H3K36me2 in the rDNA promoter on starvation. Further, it was suggested that KDM2A that bound to the rDNA promoter was activated on starvation. Our results demonstrate that KDM2A binds to the rDNA promoter with unmethylated CpG sequences via the CxxC-ZF domain, demethylates H3K36me2 in the rDNA promoter in response to starvation in a JmjC domain-dependent manner, and reduces rDNA transcription.
    Cell Structure and Function 02/2014; DOI:10.1247/csf.13022
  • [Show abstract] [Hide abstract]
    ABSTRACT: Protein Kinase D (PKD) 1, 2, and 3 are members of the PKD family. PKDs influence many cellular processes, including cell polarity, structure of the Golgi, polarized transport from the Golgi to the basolateral plasma membrane and actin polymerization. However, the role of the PKD family in cell polarity has not yet been elucidated in vivo. Here, we show that KO mice displayed similar localization of the apical and basolateral proteins, transport of VSV-G and a GPI-anchored protein, and similar localization of actin filaments. As DKO mice were embryonic lethal, we generated MEFs that lacked all PKD isoforms from the PKD1 and PKD2 double floxed mice using Cre recombinase and PKD3 siRNA. We observed a similar localization of various organelles, a similar time course in the transport of VSV-G and a GPI-anchored protein, and a similar distribution of F-actin in the PKD-null MEFs. Collectively, our results demonstrate that the complete deletion of PKDs does not affect the transport of VSV-G or a GPI-anchored protein, and the distribution of F-actin. However, simultaneous deletion of PKD1 and PKD2 affect embryonic development, demonstrating their functional redundancy during development.
    Cell Structure and Function 01/2014; DOI:10.1247/csf.13020
  • [Show abstract] [Hide abstract]
    ABSTRACT: The microtubule (MT) cytoskeleton is essential for cellular morphogenesis, cell migration, and cell division. MT organization is primarily mediated by a variety of MT-associated proteins. Among these proteins, plus-end-tracking proteins (+TIPs) are evolutionarily conserved factors that selectively accumulate at growing MT plus ends. Cytoplasmic linker protein (CLIP) -170 is a +TIP that associates with diverse proteins to determine the behavior of MT ends and their linkage to intracellular structures, including mitotic chromosomes. However, how CLIP-170 activity is spatially and temporally controlled is largely unknown. Here, we show that phosphorylation at Ser312 in the third serine-rich region of CLIP-170 is increased during mitosis. Polo-like kinase 1 (Plk1) is responsible for this phosphorylation during the mitotic phase of dividing cells. In vitro analysis using a purified CLIP-170 N-terminal fragment showed that phosphorylation by Plk1 diminishes CLIP-170 binding to the MT ends and lattice without affecting binding to EB3. Furthermore, we demonstrate that during mitosis, stable kinetochore/MT attachment and subsequent chromosome alignment require CLIP-170 and a proper phosphorylation/dephosphorylation cycle at Ser312. We propose that CLIP-170 phosphorylation by Plk1 regulates proper chromosome alignment by modulating the interaction between CLIP-170 and MTs in mitotic cells and that CLIP-170 activity is stringently controlled by its phosphorylation state, which depends on the cellular context.
    Cell Structure and Function 01/2014; DOI:10.1247/csf.14001
  • [Show abstract] [Hide abstract]
    ABSTRACT: Multiple type I and II hair keratins are expressed in hair-forming cells but the role of each protein in hair fiber formation remains obscure. In this study, recombinant proteins of human type I hair keratins (K35, K36 and K38) and type II hair keratins (K81 and K85) were prepared using bacterial expression systems. The heterotypic subunit interactions between the type I and II hair keratins were characterized using two-dimensional gel electrophoresis and surface plasmon resonance (SPR). Gel electrophoresis showed that the heterotypic complex-forming urea concentrations differ depending on the combination of keratins. K35-K85 and K36-K81 formed relatively stable heterotypic complexes. SPR revealed that soluble K35 bound to immobilized K85 with a higher affinity than to immobilized K81. The in vitro intermediate filament (IF) assembly of the hair keratins was explored by negative-staining electron microscopy. While K35-K81, K36-K81 and K35-K36-K81 formed IFs, K35-K85 afforded tight bundles of short IFs and large paracrystalline assemblies, and K36-K85 formed IF tangles. K85 promotes lateral association rather than elongation of short IFs. The in vitro assembly properties of hair keratins depended on the combination of type I and II hair keratins. Our data suggest the functional significance of K35-K85 and K36-K81 with distinct assembly properties in the formation of macrofibrils.
    Cell Structure and Function 01/2014; DOI:10.1247/csf.13021
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microfold (M) cells are intestinal epithelial cells specialized for sampling and transport of luminal antigens to gut-associated lymphoid tissue for initiation of both mucosal and systemic immune responses. Therefore, M-cell targeted vaccination has the potential to be a better immunization strategy. Glycoprotein 2 (GP2), an antigen uptake receptor for FimH(+) bacteria on M cells, can be a good target for this purpose. Aptamers are oligonucleotides that bind to a variety of target molecules with high specificity and affinity. Together with its low toxic feature, aptamers serves as a tool of molecular-targeted delivery. In this study, we used Systematic Evolution of Ligands by EXponential enrichment (SELEX) to isolate aptamers specific to murine GP2 (mGP2). After ten rounds of SELEX, eleven different aptamer sequences were selected. Among them, the most frequently appeared sequence (~60%) were aptamer NO.1 (Apt1), and the second most (~7%) were aptamer NO.5 (Apt5). In vitro binding experiment confirmed that only Apt1 and Apt5 specifically bound to mGP2 among eleven aptamers initially selected. Apt1 showed the strongest affinity with mGP2, with the Kd value of 110 ± 2.6 nM evaluated by BIACORE. Binding assays with mutants of Apt1 suggest that, in addition to the loop structure, the nucleotide sequence, AAAUA, in the loop is important for binding to mGP2. Furthermore, this aptamer was able to bind to mGP2 expressed on the cell surface. These results suggest that this mGP2-specific aptamer could serve as a valuable tool for testing M-cell-targeted vaccine delivery in the murine model system.
    Cell Structure and Function 12/2013; DOI:10.1247/csf.13019
  • [Show abstract] [Hide abstract]
    ABSTRACT: The paracellular pathway of an epithelial cellular sheet can be divided into two parts: one between two adjacent cells sealed by tight junctions (TJs) and one at tricellular contacts (TCs), where the corners of three cells meet. At TCs of epithelial cells, there is a specialized mode of TJs, namely tricellular TJs (tTJs), required for full barrier function of the cellular sheet. However, tTJs have not been described in endothelial cells to date. Here, we investigated whether tTJs occur in endothelial cells by analyzing the TC localizations of tTJ markers, tricellulin and angulin family proteins (angulin-1/LSR, angulin-2/ILDR1, and angulin-3/ILDR2), by immunofluorescence staining of frozen sections of various tissues from adult mice. Endothelial TCs in most tissues revealed no detectable staining of tricellulin or angulins. However, tricellulin and angulin-1/LSR were specifically concentrated in TCs of brain and retinal endothelial cells, which form the blood-brain barrier (BBB) and inner blood-retinal barrier (BRB), respectively. Even in the brain, endothelial cells in the choroid plexus and the median eminence, one of the circumventricular organs, did not show concentration of tricellulin or angulins at TCs. These findings indicate the existence of tTJs in endothelial cells in vivo and suggest that tTJs impart important characteristics to the BBB and inner BRB.
    Cell Structure and Function 11/2013; DOI:10.1247/csf.13015
  • [Show abstract] [Hide abstract]
    ABSTRACT: The serine/threonine kinase Akt plays a critical role in cell proliferation, survival, and tumorigenesis. As a central kinase in the phosphatidylinositol 3-kinase pathway, its activation mechanism at the plasma membrane has been well characterized. However, the subcellular Akt activity in living cells is still largely unknown. Fluorescence resonance energy transfer (FRET)-based biosensors have emerged as indispensable tools to visualize the subcellular activities of signaling molecules. In this study, we developed a highly specific FRET biosensor for Akt based on the Eevee backbone, called Eevee-iAkt. Using inhibitors targeting kinases upstream and downstream of Akt, we showed that Eevee-iAkt specifically monitors Akt activity in living cells. To visualize Akt activity at different subcellular compartments, we targeted Eevee-iAkt to raft and non-raft regions of the plasma membrane, mitochondria, and nucleus in HeLa and Cos7 cells. Interestingly, we revealed substantial differences in Akt activation between HeLa and Cos7 cells upon epidermal growth factor (EGF) stimulation: Akt was transiently activated in HeLa cells with comparable levels at the plasma membrane, cytosol, and mitochondria. In contrast, sustained and spatially localized Akt activation was observed in EGF-stimulated Cos7 cells. We found high Akt activity at the plasma membrane, low activity in the cytosol, and no detectable activity at the mitochondria and nucleus in Cos7 cells. The Eevee-iAkt biosensor was shown to be a valuable tool to study the functional relationship between subcellular Akt activation and its anti-apoptotic role in living cells.
    Cell Structure and Function 11/2013; DOI:10.1247/csf.13018
  • [Show abstract] [Hide abstract]
    ABSTRACT: Remodeling of collagen fibrils is involved in a variety of physiological and pathological processes including development, tissue repair, and metastasis. Fibroblast-populated collagen gel contraction has been employed as a model system to investigate the collagen fibril remodeling within three-dimensional collagen matrices. Research on collagen gel contraction is also important for understanding the mechanism underlying connective tissue repair, and for design considerations for engineered tissues in regenerative medicine. Second harmonic generation (SHG) is a non-linier optical effect by which well-ordered protein assemblies, including collagen fibrils, can be visualized without any labeling, and used for a noninvasive imaging of collagen fibrils in the skin. Here we demonstrate that the remodeling of collagen fibrils in the fibroblast-populated collagen gel can be analyzed by SHG imaging with a multiphoton microscope. Two models of collagen gel contraction (freely versus restrained contraction) were prepared, and orientation of fibroblasts, density, diameter, and distribution of collagen fibrils were examined by multiphoton fluorescent and SHG microscopy. Three-dimensional construction images revealed vertical and horizontal orientation of fibroblasts in freely and restrained gel contraction, respectively. Quantitative analysis indicated that collagen fibrils were accumulated within the gel and assembled into the thicker bundles in freely but not restrained collagen gel contraction. We also found that actomyosin contractility was involved in collagen fibril remodeling. This study elucidates how collagen fibrils are remodeled by fibroblasts in collagen gel contraction, and also proves that SHG microscopy can be used for the investigation of the fibroblast-populated collagen gel.
    Cell Structure and Function 10/2013; DOI:10.1247/csf.13017
  • [Show abstract] [Hide abstract]
    ABSTRACT: The Prdm (PRDI-BF1-RIZ1 homologous) family is involved in cell differentiation, and several Prdms have been reported to methylate histone H3 by intrinsic or extrinsic pathways. Here, we report that Prdm12 recruits G9a to methylate histone H3 on lysine 9 through its zinc finger domains. Because of the expression of Prdm12 in the developmental nervous system, we investigated the role of Prdm12 on P19 embryonic carcinoma cells as a model system for neurogenesis. In P19 cells, Prdm12 is induced by Retinoic acid (RA). Overproduction of Prdm12 in P19 cells impairs cell proliferation and increases the G1 population accompanied by the upregulation of p27. In contrast, the knockdown of Prdm12 increases the number of cells in a suspension culture of RA-induced neural differentiation. Both the PR domain and zinc finger domains are required for the anti-proliferative activity of Prdm12. While the data in this study is based on in vitro models, the results suggest that Prdm12 is induced by the RA signaling in vivo, and may regulate neural differentiation during animal development.
    Cell Structure and Function 07/2013; DOI:10.1247/csf.13010
  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients with schizophrenia receive medication to alleviate various symptoms, but some efficacious second generation antipsychotics, particularly olanzapine, can cause obesity, dyslipidemia, and diabetes mellitus. It has been generally considered that olanzapine contributes to the development of diabetes by inducing obesity and subsequent insulin resistance. In this study, we examined the effect of olanzapine and risperidone, another second generation antipsychotic, on a hamster pancreatic β cell line, and found that both evoked mild endoplasmic reticulum (ER) stress, as evidenced by mild activation of the ER stress sensor molecule PERK. Surprisingly, only olanzapine induced marked apoptosis. Phosphorylation of the α subunit of eukaryotic initiation factor 2, an event immediately downstream of PERK activation, was not observed in cells treated with olanzapine, protein synthesis continued despite PERK activation, and ER stress was thereby sustained. Secretion of insulin was markedly inhibited, and both proinsulin and insulin accumulated inside olanzapine-treated cells. Inhibition of protein synthesis and knockdown of insulin mRNA, which result in less unfolded protein burden, both attenuated subsequent olanzapine-induced apoptosis. Given clinical observations that some patients taking olanzapine exhibit hyperlipidemia and hyperglycemia without gaining weight, our observations suggest that damage to pancreatic β cells may contribute to the undesirable metabolic consequences of olanzapine treatment in some cases.
    Cell Structure and Function 06/2013; DOI:10.1247/csf.13012