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Regulation of Cell Functions
Published in Enrique Pimentel, Handbook of Growth Factors, 2017
Gene transcripts encoding an intracellular protein, prohibitin, were identified through their expression in higher than normal regenerating liver.539,540 Prohibitin is expressed in different tissues of the adult rat and is a protein highly conserved in evolution. Expression of prohibitin blocks DNA synthesis in both normal and tumor cells, and microinjection of an oligonucleotide containing prohibitin sequences into human fibroblasts stimulates entry of cells into the S phase. The prohibitin gene, pro-1, encodes a 30-kDa protein of 272 amino acids which does not appear to contain ATP-binding sites or nuclear localization signals. The human pro-1 gene is located on chromosome region 17q21 and is mutated in some sporadic breast cancers.541 The pro-1 gene is the mammalian analog of Cc, a Drosophila gene that is vital for the normal development of the insect. Prohibitin could have a universal role in the negative control of proliferative activity. However, the level of prohibitin mRNA in different tissues is not necessarily consistent with the growth potential of each tissue, and the product of the prohibitin gene has not been characterized.
Mitochondrial Dysfunction and Oxidative Stress in the Pathogenesis of Metabolic Syndrome
Published in Shamim I. Ahmad, Handbook of Mitochondrial Dysfunction, 2019
Furthermore, the shape of mitochondria, biogenesis ratio, turnover and dynamics, fusion/fission processes are also dynamically changing depending on the bioenergetic state of the cell65. Mitochondrial fusion is associated with active mitochondrial function whereas fission is associated with mitochondria damage and their removal by mitophagy and autophagy66. Mitofusins 1 and 2 (Mfn1 and Mfn2), the large GTPases, and autosomal dominant optic atrophy-1 (OPA1), are the main proteins involved in mitochondrial fusion. Mfn1 and Mfn2 are located at the surface of the outer membrane of mitochondria and act in the fusion process of these membranes whereas OPA1 is an intermembrane protein anchored to the inner membrane and acts in the fusion of inner membranes67,68. Mfn2 is also involved in tethering mitochondria with endoplasmic reticulum (ER) which regulates the communication between mitochondria and ER, particularly in nutrient-surplus induced ER stress in metabolic syndrome69–71. In mitochondrial fission, the dynamin related protein 1 (DRP1) and the fission protein 1 (FIS1) are the main proteins involved in this process. DRP1 is a GTPase located mainly in the cytosol with a fraction localized at punctate structures on the outer mitochondria membrane72. FIS1 is a protein integrated in the outer mitochondrial membrane that recruits DRP173,74. Another regulatory protein, prohibitin, is a complex of two proteins, PHB-1 and PHB-2, which are ubiquitous and form a ring-like complex at the inner membrane of the mitochondria75 where prohibitin stabilizes OPA1 and regulates mitochondrial fusion and cristae morphogenesis. However, the exact molecular mechanism of this complex in lipid overload-induced mitochondrial dysfunction and oxidative stress response remains unclear at the present time76,77.
The front line of research into immunoglobin G4-related disease - Do autoantibodies cause immunoglobin G4-related disease?
Published in Modern Rheumatology, 2019
Hisanori Umehara, Kazuichi Okazaki, Mitsuhiro Kawano, Yoshiya Tanaka
Chinese scientists have identified prohibitin, as a candidate autoantigen of IgG4-RD by affinity purification with patient serum and matrix-assisted laser desorption/ionization time-of-flight tandem (MALDI-TOF/TOF) mass spectrometry [32]. The antibody against prohibitin was found to be 73% positive in patients with IgG4-AIP, 53% in those with IgG4-Mikulizz’s disease, 54% in IgG4-retroperitoneal fibrosis and 89% positive in other patients with probable IgG4-RD, respectively. Whereas, this antibody was detected in only 13% of patients with Sjogren’s syndrome and 1% in healthy controls. Prohibitin is ubiquitously expressed and possesses multiple functions, positively or negatively, in cell proliferation, cell cycle, transcription and signal transduction [33]. In addition, prohibitin binds to DNA and numerous proteins such as complement component C3a and C3b, Annexin A2, protein C, and more [34,35]. Although the function of prohibitin in IgG4-RD is unclear, the antibody against prohibitin may have a role in the mechanism of IgG4-RD.
Precipitation with polyethylene glycol followed by washing and pelleting by ultracentrifugation enriches extracellular vesicles from tissue culture supernatants in small and large scales
Published in Journal of Extracellular Vesicles, 2018
Anna-Kristin Ludwig, Kyra De Miroschedji, Thorsten R. Doeppner, Verena Börger, Johannes Ruesing, Vera Rebmann, Stephan Durst, Sören Jansen, Michel Bremer, Elmar Behrmann, Bernhard B. Singer, Holger Jastrow, Jan Dominik Kuhlmann, Fouzi El Magraoui, Helmut E. Meyer, Dirk M. Hermann, Bertram Opalka, Stefan Raunser, Matthias Epple, Peter A. Horn, Bernd Giebel
To document enrichment of the EVs during the PEG 6000 precipitation procedure, western blot analyses for CD81, CD9, HSP70 and Tsg101 were performed on samples of the conditioned media from cells of all four HEK293T-CD63-eGFP clones, on the supernatants and the pellets of the 6,000 × g centrifugation step, the PEG pellets and on the supernatants and the pellets of the final ultracentrifugation procedure. CD81, CD9 and Tsg101 were detected in all PEG pellets and in a more enriched manner in the final samples (Suppl. Figure 2A). Parts of the HSP70 were also found in the supernatant of the ultracentrifugation pellet, resulting in comparable HSP70 concentrations in PEG and ultracentrifugation pellets (Suppl. Figure 2A). In a representative manner, corresponding samples obtained from HEK293T-CD63-eGFP clones E7 and B2 conditioned media were also probed with anti-BSA antibodies. Here, an opposite picture was obtained. BSA was detected in high amounts in the conditioned media and the supernatants and pellets of the 6,000 × g centrifugation step. Massively reduced BSA levels were detected in the PEG pellet and the supernatant of the final ultracentrifugation step but not in the final EV fraction, which – on the same blot – showed strong enrichment of CD81 (Suppl. Figure 2B). The mitochondrial protein Prohibitin was used as a representative marker to detect contaminations caused by cell organelles. It was detected in cell lysates but not in any of the conditioned media fractions (data not shown).
Optimization of siRNA delivery to target sites: issues and future directions
Published in Expert Opinion on Drug Delivery, 2018
Ikramy A. Khalil, Yuma Yamada, Hideyoshi Harashima
Targeting endothelial cells of different organs is another strategy for targeting organs other than the liver. For example, in a previous study, we reported that the peptide GALA(WEAALAEALAEALAEHLAEALAEALEALAA) has the ability to efficiently target lung endothelial cells [94]. Similarly, the polymeric 7C1 system was used for the targeted delivery of siRNA to the lung endothelium [66]. A prohibitin targeted peptide was also successfully used to target the vascular endothelium in adipose tissues [95]. Meanwhile, ligands that undergo transcytosis must be used to pass the endothelial barrier. The use of transcytosis to cross the vascular system is still an inefficient process and represents one of the best candidates for optimizing delivery to tissues other than the liver, the spleen, and tumors [96].