| 1. |
- Abdrakhmanov, A, et al.
(författare)
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Involvement of mitophagy in cisplatin-induced cell death regulation
- 2019
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Ingår i: Biological chemistry. - : Walter de Gruyter GmbH. - 1437-4315 .- 1431-6730. ; 400:2, s. 161-170
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Tidskriftsartikel (refereegranskat)abstract
- Mitophagy, the selective degradation of mitochondria via the autophagic pathway, is a vital mechanism of mitochondrial quality control in cells. The removal of malfunctioning or damaged mitochondria is essential for normal cellular physiology and tissue development. Stimulation of mitochondrial permeabilization and release of proapoptotic factors from the intermembrane space is an essential step in triggering the mitochondrial pathway of cell death. In this study, we analyzed the extent to which mitophagy interferes with cell death, attenuating the efficiency of cancer therapy. We show that stimulation of mitophagy suppressed cisplatin-induced apoptosis, while mitophagy inhibition stimulates apoptosis and autophagy. Suppression of mitophagy involved production of reactive oxygen species, and the fate of cell was dependent on the interplay between endoplasmic reticulum stress and autophagy.
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| 2. |
- Akoachere, Monique, et al.
(författare)
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Characterization of the glyoxalases of the malarial parasite Plasmodium falciparum and comparison with their human counterparts.
- 2005
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Ingår i: Biol Chem. - 1431-6730. ; 386:1, s. 41-52
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Tidskriftsartikel (refereegranskat)abstract
- The glyoxalase system consisting of glyoxalase I (GloI) and glyoxalase II (GloII) constitutes a glutathione-dependent intracellular pathway converting toxic 2-oxoaldehydes, such as methylglyoxal, to the corresponding 2-hydroxyacids. Here we describe a complete glyoxalase system in the malarial parasite Plasmodium falciparum. The biochemical, kinetic and structural properties of cytosolic GloI (cGloI) and two GloIIs (cytosolic GloII named cGloII, and tGloII preceded by a targeting sequence) were directly compared with the respective isofunctional host enzymes. cGloI and cGloII exhibit lower K(m) values and higher catalytic efficiencies (k(cat)/K(m) ) than the human counterparts, pointing to the importance of the system in malarial parasites. A Tyr185Phe mutant of cGloII shows a 2.5-fold increase in K(m) , proving the contribution of Tyr185 to substrate binding. Molecular models suggest very similar active sites/metal binding sites of parasite and host cell enzymes. However, a fourth protein, which has highest similarities to GloI, was found to be unique for malarial parasites; it is likely to act in the apicoplast, and has as yet undefined substrate specificity. Various S-(N-hydroxy-N-arylcarbamoyl)glutathiones tested as P. falciparum Glo inhibitors were active in the lower nanomolar range. The Glo system of Plasmodium will be further evaluated as a target for the development of antimalarial drugs.
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| 3. |
- Appelros, Stefan, et al.
(författare)
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Studies on the turnover of procarboxypeptidase B, its active enzyme and the activation peptide in the pig
- 1998
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Ingår i: Biological Chemistry. - : Walter de Gruyter GmbH. - 1437-4315. ; 379:7, s. 893-898
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Tidskriftsartikel (refereegranskat)abstract
- Recent developments in the treatment of acute pancreatitis have focused on the importance of early determination of the severity of an attack. Measuring levels of activation peptides from pancreatic proenzymes seems to be one way to predict severity. Levels of the activation peptide from procarboxypeptidase B, in both serum and urine on admission, have been shown to correlate to the outcome. To be able to interpret levels of this peptide in serum and urine under normal and in various acute abdominal conditions, we need knowledge about its turnover in the circulation. Procarboxypeptidase B, active carboxypeptidase and the activation peptide were therefore purified from porcine pancreatic juice. These proteins were labelled with 125I or 131I and their turnovers were studied in vivo in the pig. The proenzyme and the activation peptide were eliminated without interaction with any substance in the circulation. The active enzyme was to some degree bound to a substance with a molecular mass of 10-20 kDa. Active CPB was eliminated more slowly than proCPB and the activation peptide. Five percent of the activation peptide was detected nondegraded in the urine. After intraduodenal administration of the activation peptide there was no sign of the peptide in the urine.
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| 4. |
- Arampatzidou, Maria, et al.
(författare)
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Effects of cathepsin K deficiency on intercellular junction proteins, luminal mucus layers, and extracellular matrix constituents in the mouse colon.
- 2012
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Ingår i: Biological chemistry. - : Walter de Gruyter GmbH. - 1437-4315. ; 393:12, s. 1391-403
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Tidskriftsartikel (refereegranskat)abstract
- Cathepsin K has been shown to exhibit antimicrobial and anti-inflammatory activities in the mouse colon. To further elucidate its role, we used Ctsk-/- mice and demonstrated that the absence of cathepsin K was accompanied by elevated protein levels of related cysteine cathepsins (cathepsins B, L, and X) in the colon. In principle, such changes could result in altered subcellular localization; however, the trafficking of cysteine cathepsins was not affected in the colon of Ctsk-/- mice. However, cathepsin K deficiency affected the extracellular matrix constituents, as higher amounts of collagen IV and laminin were observed. Moreover, the localization pattern of the intercellular junction proteins E-cadherin and occludin was altered in the colon of Ctsk-/- mice, suggesting potential impairment of the barrier function. Thus, we used an ex vivo method for assessing the mucus layers and showed that the absence of cathepsin K had no influence on mucus organization and growth. The data of this study support the notion that cathepsin K contributes to intestinal homeostasis and tissue architecture, but the lack of cathepsin K activity is not expected to affect the mucus-depending barrier functions of the mouse colon. These results are important with regard to oral administration of cathepsin K inhibitors that are currently under investigation in clinical trials.
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| 5. |
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| 6. |
- Aspenstrom, P
(författare)
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Atypical Rho GTPases RhoD and Rif integrate cytoskeletal dynamics and membrane trafficking
- 2014
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Ingår i: Biological chemistry. - : Walter de Gruyter GmbH. - 1437-4315 .- 1431-6730. ; 395:5, s. 477-484
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Tidskriftsartikel (refereegranskat)abstract
- The Rho GTPases are essential regulators of basic cellular processes, including cell migration, cell contraction and cell division. Most studies still involve just the three canonical members, RhoA, Rac1 and Cdc42, although the Rho GTPases comprise at least 20 members. The aim of this review is to highlight some of the recent advances in our knowledge regarding the less-studied Rho members, with the focus on RhoD and Rif. The phenotypic alterations to cell behaviour that are triggered by RhoD and Rif suggest that they have unique impacts on cytoskeletal dynamics that distinguish them from the well-studied members of the Rho GTPases. In addition, RhoD has a role in the regulation of intracellular transport of vesicles. Taken together, the available data indicate that RhoD and Rif have functions as master regulators in the integration of cytoskeletal reorganisation and membrane trafficking.
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| 7. |
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| 8. |
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| 9. |
- Bhushan, Shashi, et al.
(författare)
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Proteolytic mechanism of a novel mitochondrial and chloroplastic PreP peptidasome.
- 2006
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Ingår i: Biol Chem. - 1431-6730. ; 387:8, s. 1087-90
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Tidskriftsartikel (refereegranskat)abstract
- The 2.1-A-resolution crystal structure of the novel mitochondrial and chloroplastic metalloendopeptidase, AtPreP1, revealed a unique peptidasome structure, in which the two halves of the enzyme completely enfold a huge proteolytic cavity. Based on the structure, we proposed a novel mechanism for proteolysis involving hinge-bending motions, which cause the protease to open and close in response to substrate binding. We generated four double-mutants of AtPreP1 by introducing cysteines at positions where disulfide bonds can be formed in order to lock and unlock the protease and tested the activity under oxidizing and reducing conditions. The overall results support the proposed mechanism.
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| 10. |
- Bjorkqvist, J, et al.
(författare)
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Zinc-dependent contact system activation induces vascular leakage and hypotension in rodents
- 2013
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Ingår i: Biological chemistry. - : Walter de Gruyter GmbH. - 1437-4315. ; 394:9, s. 1195-1204
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Tidskriftsartikel (refereegranskat)abstract
- Contact to polyanions induces autoactivation of the serine protease factor XII that triggers the kallikrei-kinin system. Recent studies indicate that polysaccharide-induced autoactivation of factor XII has a role in allergy-related vascular leakage, and angioedema. Here, we characterize in vivo effects of the synthetic polysaccharide dextran sulfate in human plasma and in rodent models. Minute amounts of high-molecular-weight dextran sulfate-initiated factor XII-autoactivation and triggered formation of the inflammatory mediator bradykinin via plasma kallikrein-mediated cleavage of high-molecular-weight kininogen. High-molecular-weight kininogen fragments, containing the HKH20 sequence in domain D5H, blocked dextran sulfate-initiated bradykinin-generation by depleting plasma Zn2+ ions. Topical application of high molecular weight dextran sulfate increased leakage in murine skin microvessels, in a bradykinin-dependent manner. Intravital laser scanning microscopy showed a greater than two-fold elevated and accelerated fluid extravasation in C1 esterase inhibitor deficient mice that lack the major inhibitor of factor XII, compared to wild-type controls. Intra-arterial infusion of dextran sulfate induced a rapid transient drop in arterial blood pressure in rats and preinjection of kinin B2 receptor antagonists or HKH20 peptide blunted dextran sulfate-triggered hypotensive reactions. The data characterize dextran sulfate as a potent in vivo activator of factor XII with implications for bradykinin-mediated vascular permeability and blood pressure control.
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