Heat shock protein coinducers with no effect on protein denaturation specifically modulate the membrane lipid phase

Török, Zsolt; Tsvetkova, Nelly M.; Balogh, Gábor; Horváth, Ibolya; Nagy, Enikő; Pénzes, Zoltán; Hargitai, Judit; Bensaude, Olivier; Csermely, Péter; Crowe, John H.; Maresca, Bruno; Vı́gh, László

doi:10.1073/pnas.0438003100

Cited by 87 publications

(35 citation statements)

References 35 publications

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“…impaired glucose tolerance (30). BGP-15 is thought to activate HSP72 via modification of membrane microdomain-associated stress-sensing and -signaling mechanisms (50,52) and by prolonging the binding of HSF1 to heat shock response element (27). Since GGA causes rapid activation of HSF1 itself, the mechanisms of induction of HSP72 and its operant organ may be different from those of BGP-15.…”

Section: Discussionmentioning

confidence: 99%

An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice

Adachi

Kondo

Ogawa

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Section: Discussionmentioning

confidence: 99%

An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice

Adachi

Kondo

Ogawa

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…The translocation process is also temperature-dependent, presumably due to the well known temperature-dependent lipid phase transition of the phospholipid bilayer (25).…”

Section: Discussionmentioning

confidence: 99%

Receptor/Transporter-independent Targeting of Functional Peptides across the Plasma Membrane

Veach

Liu

Yao

et al. 2004

Journal of Biological Chemistry

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Targeting of peptides, proteins, and other functional cargo into living cells is contingent upon efficient transport across the plasma membrane barrier. We have harnessed the signal sequence hydrophobic region (SSHR) to deliver functional cargoes to cultured cells and to experimental animals. We now report evidence that two chirally distinct forms of SSHR composed of all L or all D amino acids showed similar membrane-translocating activity as assessed by confocal microscopy, flow cytometry, and direct fluorescence measurement. An attached nuclear localization sequence ferried by the SSHR enantiomers displayed similar intracellular function by inhibiting inducible nuclear import of transcription factor nuclear factor B and suppressing nuclear factor B-dependent gene expression of cytokines. A nuclear localization sequence comprised of a positively charged cluster of amino acids was rapidly translocated by SSHR enantiomers to the interior of unilamellar phospholipid vesicles. These findings indicate that the SSHR translocates functional peptides directly through the plasma membrane phospholipid bilayer without involving chirally specific receptor/transporter mechanisms. This mechanism of SSHR translocation is suitable for facile delivery of biologically active peptides for cell-based and animal-based functional proteomic studies.The plasma membrane imposes tight control on the access of extracellular peptides and proteins to the cell interior. Through its mosaic structure of proteins and glycolipids embedded into the phospholipid bilayer, the plasma membrane provides a boundary for the 10,000 -15,000 proteins expressed in a typical mammalian cell (1, 2). Despite this barrier, transfer of information across the membrane is essential for cell development, function, and survival. Membrane receptors and transporters sense the extracellular environment of growth-promoting or -inhibiting ligands, short peptides, ions, and nutrients. This recognition allows their cellular uptake through specific receptor-mediated endocytosis or transporter-based translocation. To bypass these inherent mainstays of the plasma membrane functional integrity, we harnessed a signal sequence-derived hydrophobic region to deliver functional cargoes composed of peptides and proteins to probe and modulate intracellular signaling (3, 4). However, the mechanism of SSHR 1 -directed translocation of functional cargo across the plasma membrane remains unexplained.The overall structure of signal peptides is conserved in evolution between prokaryotes and eukaryotes, although the sequences of signal peptides are highly diverse (5). Their tripartite structure comprises an NH 2 -terminal region (n region), and a hydrophobic h region of variable length; this is followed by a cleavage site (c region) for signal peptidase. The hydrophobic region, which usually forms a helix, is endowed with a membrane-translocating activity (6). Its primary function is to guide a nascent polypeptide chain from the ribosomal tunnel through a translocon pore that is open latera...

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“…Tumor cells with high levels of membrane-bound Hsp70 have high rates of cell growth and metastasis (4) and are more effectively killed by natural killer cells (27,29). Similarly, the hydroxylamine derivative bimoclomol induced membrane-bound Hsp70 that stabilized membrane fluidity at elevated temperatures (69). Interestingly, membrane-bound Hsp70 may also be interacting with the insulin receptor (73).…”

Section: Discussionmentioning

confidence: 99%

Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts

Ali²,

Currie³

2006

American Journal of Physiology-Heart and Circulatory Physiology

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Li, Gefeng, Imtiaz S. Ali, and R. William Currie. Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts. Am J Physiol Heart Circ Physiol 291: H1709 -H1721, 2006. First published May 26, 2006 doi:10.1152/ajpheart.00201.2006.-Insulin induces the expression of the 70-kDa heat shock protein (Hsp70) in rat hearts. In this study, we examined insulin-and heat shock-treated hearts for improved contractile recovery after 30 min of ischemia, activation of the heat shock transcription factor, and localization of the Hsp70 in relation to dystrophin and ␣-tubulin. Adult male SpragueDawley rats were assigned to groups: 1) control, 2) sham control, 3) insulin injected (200 U/g body wt), 4) heat shock treated (core body temperature 42°C for 15 min), and 5) heat shock and insulin treated. Six hours later, hearts were isolated for Langendorff perfusion to determine cardiac function, or myocardial tissues were collected and prepared for either electrophoretic mobility shift assay, Western blot analysis, or immunofluorescence microscopy. Insulin treatment with 6 h of recovery enhances postischemic myocardial recovery of contractile function and increases Hsp70 expression through activation of the heat shock transcription factor. Insulin-treated hearts had elevated levels of Hsp70, particularly in the membrane fraction. In contrast, heat-shocked hearts had elevated levels of Hsp70 in the cytosol, membrane, and pellet fractions. After insulin treatment, Hsp70 was mostly colocalized to the plasma membrane with dystrophin. In contrast, after heat shock, Hsp70 was localized mostly between cardiomyocytes in apparent vascular or perivascular elements. The localization of Hsp70 is dependent on the inducing stimuli of either heat shock or insulin treatment. The cell membrane versus vascular localization of Hsp70 suggests the interesting possibility of functionally distinct roles for Hsp70 in the heart, whether induced by insulin or heat shock treatment. heat shock; heat shock protein 70; heat shock transcription factor; ischemia/reperfusion INSULIN IS A CRUCIAL REGULATOR of metabolism, and in cardiac muscle, insulin induces glycogen and protein synthesis, and in fat, lipid storage is favored. Insulin also mediates other diverse effects in a wide variety of cells and tissues (57). Sodi-Pallares et al. (67) initially introduced the concept of infusing a metabolic cocktail of glucose, insulin, and potassium to improve recovery from myocardial infarction. Clinical studies (20,22,63) suggest that this cocktail might have an important role in reducing in-hospital mortality after acute cardiac infarction. Initially, two possible mechanisms for the effectiveness of the glucose, insulin, and potassium cocktail were suggested: 1) the promotion of cardiac glycolysis and 2) the uptake of free fatty acids into adipocytes (58). More recently, insulin alone has been shown to be as effective as the glucose, insulin, and potassium cocktail at reducing myocardial ischemia-reperfusion injury (32). The cardioprotective...

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Heat shock protein coinducers with no effect on protein denaturation specifically modulate the membrane lipid phase

Cited by 87 publications

References 35 publications

An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice

An acylic polyisoprenoid derivative, geranylgeranylacetone protects against visceral adiposity and insulin resistance in high-fat-fed mice

Receptor/Transporter-independent Targeting of Functional Peptides across the Plasma Membrane

Insulin induces myocardial protection and Hsp70 localization to plasma membranes in rat hearts

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