Browsing tag: apoptoza

Charakterystyka genotoksyn CDT (cytolethal distending toxin)

Characterization of CDT (cytolethal distending toxin) genotoxins
P. Kobierecka, A. Wyszynska, E. K. Jagusztyn - Krynicka

1. Wstęp. 2. Ogólna charakterystyka CDT – operon cdt. 3. Rola podjednostek toksyny. 4. Mechanizm składania dojrzałej toksyny, struktura CDT. 5. Losy CDT w komórkach docelowych. 6. Mechanizm intoksykacji komórki przez toksyny CDT. 7. Nietypowa toksyna CDT wytwarzana przez Salmonella enterica sv. Typhimurium. 8. Podsumowanie

Abstract: The cytolethal distending toxins (CDTs) comprise a family of intracellulary acting bacterial protein genotoxins, produced by a variety of Gram-negative pathogenic bacteria, which cause DNA damage in the target cells. The DNA damage-response in the initiated cell results in the characteristic and irreversible cell cycle arrest and apoptosis in a broad range of mammalian cell cultures. Most of CDTs are AB2 toxins composed of three different subunits: CdtA and CdtC, both exhibiting a lectin-type fold, and CdtB, which is the active component of the complex, with DNase I and phosphatase activity. Although it is generally accepted that CdtA and CdtC, required for full activity of the CdtB, mediate its delivery into host cells, their precise role in the process remains poorly understood. Also the mechanism of toxin secretion and the mechanisms of cell surface binding, uptake and trafficking require further investigation. Some bacteria utilize OMVs to secrete CDTs. After internalization by dynamin-dependent endocytosis which requires the intact lipid rafts, toxin is retrograde transported through Golgi complex and the endoplasmic reticulum into the cell nuclear compartment, where CdtB exerts its toxic activity. CDTs are virulence determinants playing an important role in the pathogenesis of several bacterial diseases associated, for example, with human infections by Campylobacter jejuni, Escherichia coli and Aggregatibacter actinomycetemcomitans.
This review encompasses recent work on CDTs and focuses on the CDTs structure as well as on the molecular mechanisms of toxin uptake and cell’s intoxication. We also discuss some  controversial issues and indicate questions which still remain unanswered.

1. Introduction. 2. General characterization of CDT – cdt operon. 3. Role of CDT toxin subunits. 4. Mechanisms of mature toxin assembly, CDT tertiary structure. 5. CDT uptake into host cells. 6. Mechanism of CDT cellular intoxication. 7. Untypical CDT toxin producting by Salmonella enterica sv. Typhimurium. 8. Summary

Rola mitochondriów w odporności przeciwwirusowej

The role of mitochondria in antiviral immunity
K. P. Gregorczyk, Z. Wyżewski, L. Szulc-Dąbrowska, J. Struzik, J. Szczepanowska, M. Niemiałtowski

1. Wstęp. 2. Udział mitochondriów w produkcji IFN typu I oraz cytokin prozapalnych. 3. Wirusowe mechanizmy hamowania zależnej od mitochondriów produkcji IFN typu I oraz cytokin prozapalnych. 4. Apoptoza – proces „pseudoprzeciwwirusowy”. 5. Podsumowanie

Abstract: Mitochondria, which are known as “powerhouse” of the cell, have numerous important functions in cellular metabolism and are involved in cellular innate antiviral immunity in vertebrates. They participate in an intrinsic pathway of apoptosis and production of proinflammatory cytokines and type I interferons (IFNs; α/β). These functions are essential for limiting the spread of viral infection before the stimulation of adaptive immunity. However, viruses have evolved the ability to escape from the mechanisms of immune response including those related to mitochondrial functions. Viruses can exploit these organelles in their replication cycle and/or morphogenesis process, therefore the answer to the question about the exact role of mitochondria during viral infection is not unequivocal.

1. Introduction. 2. Contribution of mitochondria in type I IFN and pro-inflammatory cytokines production. 3. Viral inhibition mechanisms of the mitochondrial-dependent production of type I IFN and pro-inflammatory cytokines. 4. Apoptosis – “pseudoantiviral” process. 5. Summary