{"title":"Formation and regulation of mitochondrial membranes.","authors":"Laila Cigana Schenkel, Marica Bakovic","doi":"10.1155/2014/709828","DOIUrl":"https://doi.org/10.1155/2014/709828","url":null,"abstract":"<p><p>Mitochondrial membrane phospholipids are essential for the mitochondrial architecture, the activity of respiratory proteins, and the transport of proteins into the mitochondria. The accumulation of phospholipids within mitochondria depends on a coordinate synthesis, degradation, and trafficking of phospholipids between the endoplasmic reticulum (ER) and mitochondria as well as intramitochondrial lipid trafficking. Several studies highlight the contribution of dietary fatty acids to the remodeling of phospholipids and mitochondrial membrane homeostasis. Understanding the role of phospholipids in the mitochondrial membrane and their metabolism will shed light on the molecular mechanisms involved in the regulation of mitochondrial function and in the mitochondrial-related diseases. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"709828"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/709828","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32160893","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":"Characterization of NGF, trkA (NGFR) , and p75 (NTR) in Retina of Mice Lacking Reelin Glycoprotein.","authors":"Bijorn Omar Balzamino, Filippo Biamonte, Graziana Esposito, Ramona Marino, Francesca Fanelli, Flavio Keller, Alessandra Micera","doi":"10.1155/2014/725928","DOIUrl":"https://doi.org/10.1155/2014/725928","url":null,"abstract":"<p><p>Both Reelin and Nerve Growth Factor (NGF) exert crucial roles in retinal development. Retinogenesis is severely impaired in E-reeler mice, a model of Reelin deficiency showing specific Green Fluorescent Protein expression in Rod Bipolar Cells (RBCs). Since no data are available on Reelin and NGF cross-talk, NGF and trkA(NGFR)/ p75(NTR) expression was investigated in retinas from E-reeler versus control mice, by confocal microscopy, Western blotting, and real time PCR analysis. A scattered increase of NGF protein was observed in the Ganglion Cell Layer and more pronounced in the Inner Nuclear Layer (INL). A selective increase of p75(NTR) was detected in most of RBCs and in other cell subtypes of INL. On the contrary, a slight trend towards a decrease was detected for trkA(NGFR), albeit not significant. Confocal data were validated by Western blot and real time PCR. Finally, the decreased trkA(NGFR)/ p75(NTR) ratio, representative of p75(NTR) increase, significantly correlated with E-reeler versus E-control. These data indicate that NGF-trkA(NGFR)/ p75(NTR) is affected in E-reeler retina and that p75(NTR) might represent the main NGF receptor involved in the process. This first NGF-trkA(NGFR)/ p75(NTR) characterization suggests that E-reeler might be suitable for exploring Reelin-NGF cross-talk, representing an additional information source in those pathologies characterized by retinal degeneration. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"725928"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/725928","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32174101","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":"Matrix gla protein binds to fibronectin and enhances cell attachment and spreading on fibronectin.","authors":"Satoru Ken Nishimoto, Miyako Nishimoto","doi":"10.1155/2014/807013","DOIUrl":"https://doi.org/10.1155/2014/807013","url":null,"abstract":"<p><p>Background. Matrix Gla protein (MGP) is a vitamin K-dependent, extracellular matrix protein. MGP is a calcification inhibitor of arteries and cartilage. However MGP is synthesized in many tissues and is especially enriched in embryonic tissues and in cancer cells. The presence of MGP in those instances does not correlate well with the calcification inhibitory role. This study explores a potential mechanism for MGP to bind to matrix proteins and alter cell matrix interactions. Methods. To determine whether MGP influences cell behavior through interaction with fibronectin, we studied MGP binding to fibronectin, the effect of MGP on fibronectin mediated cell attachment and spreading and immunolocalized MGP and fibronectin. Results. First, MGP binds to fibronectin. The binding site for MGP is in a specific fibronectin fragment, called III1-C or anastellin. The binding site for fibronectin is in a MGP C-terminal peptide comprising amino acids 61-77. Second, MGP enhances cell attachment and cell spreading on fibronectin. MGP alone does not promote cell adhesion. Third, MGP is present in fibronectin-rich regions of tissue sections. Conclusions. MGP binds to fibronectin. The presence of MGP increased cell-fibronectin interactions. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"807013"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/807013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32659299","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}
Megha Garg, Lakshmi R Perumalsamy, G V Shivashankar, Apurva Sarin
{"title":"The linker histone h1.2 is an intermediate in the apoptotic response to cytokine deprivation in T-effectors.","authors":"Megha Garg, Lakshmi R Perumalsamy, G V Shivashankar, Apurva Sarin","doi":"10.1155/2014/674753","DOIUrl":"https://doi.org/10.1155/2014/674753","url":null,"abstract":"<p><p>Tissue homeostasis is a dynamic process involving proliferation and the removal of redundant or damaged cells. This is exemplified in the coordinated deletion-triggered by limiting trophic factors/cytokines in the extracellular milieu-of differentiated T cells overproduced during the mammalian immune response. However, mechanisms by which extracellular cues are perceived and transduced as apoptotic triggers remain incompletely understood. T-effectors are dependent on cytokines for survival and undergo apoptosis following cytokine withdrawal. Here we report that leptomycin B (LMB), an inhibitor of nuclear export machinery, protected T-effectors from apoptosis implicating a nuclear intermediate in the apoptotic pathway. Evidence is presented that the linker histone H1.2 localizes to the cytoplasm, by a mechanism sensitive to regulation by LMB, to activate apoptotic signaling culminating in nuclear and mitochondrial damage in T-effectors in response to cytokine deprivation. H1.2 is detected in a complex with the proapoptotic mitochondrial resident Bak and its subcellular localization regulated by Jun-N-terminal kinase (JNK), an intermediate in the apoptotic cascade in T-effectors. These data suggest that metabolic stressors may impinge on H1.2 dynamics favoring its activity at the mitochondrion, thereby functioning as a molecular switch for T-effector apoptosis. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"674753"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/674753","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32225502","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 Mitochondrial Aminoacyl tRNA Synthetases: Genes and Syndromes.","authors":"Daria Diodato, Daniele Ghezzi, Valeria Tiranti","doi":"10.1155/2014/787956","DOIUrl":"https://doi.org/10.1155/2014/787956","url":null,"abstract":"<p><p>Mitochondrial respiratory chain (RC) disorders are a group of genetically and clinically heterogeneous diseases. This is because protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis and maintenance of mitochondria, including mitochondrial DNA (mtDNA) replication, transcription, and translation, require nuclear-encoded genes. In the past decade, a growing number of syndromes associated with dysfunction of mtDNA translation have been reported. This paper reviews the current knowledge of mutations affecting mitochondrial aminoacyl tRNAs synthetases and their role in the pathogenic mechanisms underlying the different clinical presentations. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"787956"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/787956","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32184244","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}
Italo Mario Cesari, Erika Carvalho, Mariana Figueiredo Rodrigues, Bruna Dos Santos Mendonça, Nivea Dias Amôedo, Franklin David Rumjanek
{"title":"Methyl jasmonate: putative mechanisms of action on cancer cells cycle, metabolism, and apoptosis.","authors":"Italo Mario Cesari, Erika Carvalho, Mariana Figueiredo Rodrigues, Bruna Dos Santos Mendonça, Nivea Dias Amôedo, Franklin David Rumjanek","doi":"10.1155/2014/572097","DOIUrl":"10.1155/2014/572097","url":null,"abstract":"<p><p>Methyl jasmonate (MJ), an oxylipid that induces defense-related mechanisms in plants, has been shown to be active against cancer cells both in vitro and in vivo, without affecting normal cells. Here we review most of the described MJ activities in an attempt to get an integrated view and better understanding of its multifaceted modes of action. MJ (1) arrests cell cycle, inhibiting cell growth and proliferation, (2) causes cell death through the intrinsic/extrinsic proapoptotic, p53-independent apoptotic, and nonapoptotic (necrosis) pathways, (3) detaches hexokinase from the voltage-dependent anion channel, dissociating glycolytic and mitochondrial functions, decreasing the mitochondrial membrane potential, favoring cytochrome c release and ATP depletion, activating pro-apoptotic, and inactivating antiapoptotic proteins, (4) induces reactive oxygen species mediated responses, (5) stimulates MAPK-stress signaling and redifferentiation in leukemia cells, (6) inhibits overexpressed proinflammatory enzymes in cancer cells such as aldo-keto reductase 1 and 5-lipoxygenase, and (7) inhibits cell migration and shows antiangiogenic and antimetastatic activities. Finally, MJ may act as a chemosensitizer to some chemotherapics helping to overcome drug resistant. The complete lack of toxicity to normal cells and the rapidity by which MJ causes damage to cancer cells turn MJ into a promising anticancer agent that can be used alone or in combination with other agents. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"572097"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/572097","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32191692","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":"p38δ MAPK: Emerging Roles of a Neglected Isoform.","authors":"Carol O'Callaghan, Liam J Fanning, Orla P Barry","doi":"10.1155/2014/272689","DOIUrl":"https://doi.org/10.1155/2014/272689","url":null,"abstract":"<p><p>p38δ mitogen activated protein kinase (MAPK) is a unique stress responsive protein kinase. While the p38 MAPK family as a whole has been implicated in a wide variety of biological processes, a specific role for p38δ MAPK in cellular signalling and its contribution to both physiological and pathological conditions are presently lacking. Recent emerging evidence, however, provides some insights into specific p38δ MAPK signalling. Importantly, these studies have helped to highlight functional similarities as well as differences between p38δ MAPK and the other members of the p38 MAPK family of kinases. In this review we discuss the current understanding of the molecular mechanisms underlying p38δ MAPK activity. We outline a role for p38δ MAPK in important cellular processes such as differentiation and apoptosis as well as pathological conditions such as neurodegenerative disorders, diabetes, and inflammatory disease. Interestingly, disparate roles for p38δ MAPK in tumour development have also recently been reported. Thus, we consider evidence which characterises p38δ MAPK as both a tumour promoter and a tumour suppressor. In summary, while our knowledge of p38δ MAPK has progressed somewhat since its identification in 1997, our understanding of this particular isoform in many cellular processes still strikingly lags behind that of its counterparts. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"272689"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/272689","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32744544","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}
Ade Kallas, Martin Pook, Annika Trei, Toivo Maimets
{"title":"Assessment of the Potential of CDK2 Inhibitor NU6140 to Influence the Expression of Pluripotency Markers NANOG, OCT4, and SOX2 in 2102Ep and H9 Cells.","authors":"Ade Kallas, Martin Pook, Annika Trei, Toivo Maimets","doi":"10.1155/2014/280638","DOIUrl":"https://doi.org/10.1155/2014/280638","url":null,"abstract":"<p><p>As cyclin-dependent kinases (CDKs) regulate cell cycle progression and RNA transcription, CDKs are attractive targets for creating cancer cell treatments. In this study we investigated the effects of the small molecular agent NU6140 (inhibits CDK2 and cyclin A interaction) on human embryonic stem (hES) cells and embryonal carcinoma-derived (hEC) cells via the expression of transcription factors responsible for pluripotency. A multiparameter flow cytometric method was used to follow changes in the expression of NANOG, OCT4, and SOX2 together in single cells. Both hES and hEC cells responded to NU6140 treatment by induced apoptosis and a decreased expression of NANOG, OCT4, and SOX2 in surviving cells. A higher sensitivity to NU6140 application in hES than hEC cells was detected. NU6140 treatment arrested hES and hEC cells in the G2 phase and inhibited entry into the M phase as evidenced by no significant increase in histone 3 phosphorylation. When embryoid bodies (EBs) formed from NU6104 treated hES cells were compared to EBs from untreated hES cells differences in ectodermal, endodermal, and mesodermal lineages were found. The results of this study highlight the importance of CDK2 activity in maintaining pluripotency of hES and hEC cells and in differentiation of hES cells. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"280638"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/280638","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32882094","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":"Mitochondrial stress signaling promotes cellular adaptations.","authors":"Jayne Alexandra Barbour, Nigel Turner","doi":"10.1155/2014/156020","DOIUrl":"https://doi.org/10.1155/2014/156020","url":null,"abstract":"<p><p>Mitochondrial dysfunction has been implicated in the aetiology of many complex diseases, as well as the ageing process. Much of the research on mitochondrial dysfunction has focused on how mitochondrial damage may potentiate pathological phenotypes. The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations. This involves communication of stress to the cell and successful induction of quality control responses, which include mitophagy, unfolded protein response, upregulation of antioxidant and DNA repair enzymes, morphological changes, and if all else fails apoptosis. The mitochondrion is an inherently stressful environment and we speculate that dysregulation of stress signaling or an inability to switch on these adaptations during times of mitochondrial stress may underpin mitochondrial dysfunction and hence amount to pathological states over time. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"156020"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/156020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32168412","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}
Cinzia Fabrizi, Stefania De Vito, Francesca Somma, Elena Pompili, Angela Catizone, Stefano Leone, Paola Lenzi, Francesco Fornai, Lorenzo Fumagalli
{"title":"Lithium improves survival of PC12 pheochromocytoma cells in high-density cultures and after exposure to toxic compounds.","authors":"Cinzia Fabrizi, Stefania De Vito, Francesca Somma, Elena Pompili, Angela Catizone, Stefano Leone, Paola Lenzi, Francesco Fornai, Lorenzo Fumagalli","doi":"10.1155/2014/135908","DOIUrl":"https://doi.org/10.1155/2014/135908","url":null,"abstract":"<p><p>Autophagy is an evolutionary conserved mechanism that allows for the degradation of long-lived proteins and entire organelles which are driven to lysosomes for digestion. Different kinds of stressful conditions such as starvation are able to induce autophagy. Lithium and rapamycin are potent autophagy inducers with different molecular targets. Lithium stimulates autophagy by decreasing the intracellular myo-inositol-1,4,5-triphosphate levels, while rapamycin acts through the inhibition of the mammalian target of rapamycin (mTOR). The correlation between autophagy and cell death is still a matter of debate especially in transformed cells. In fact, the execution of autophagy can protect cells from death by promptly removing damaged organelles such as mitochondria. Nevertheless, an excessive use of the autophagic machinery can drive cells to death via a sort of self-cannibalism. Our data show that lithium (used within its therapeutic window) stimulates the overgrowth of the rat Pheochromocytoma cell line PC12. Besides, lithium and rapamycin protect PC12 cells from toxic compounds such as thapsigargin and trimethyltin. Taken together these data indicate that pharmacological activation of autophagy allows for the survival of Pheochromocytoma cells in stressful conditions such as high-density cultures and exposure to toxins. </p>","PeriodicalId":39084,"journal":{"name":"International Journal of Cell Biology","volume":"2014 ","pages":"135908"},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2014/135908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32147932","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}