Exploring the Role of Oxygen in Fanconi’s Anemia

Liebetrau, Wolfgang; Rünger, Thomas M.; Bäumer, A.; Henning, Claes; Groß, Oliver; Schindler, Detlev; Poot, Martin; Hoehn, Holger

doi:10.1007/978-3-642-60393-8_25

Cited by 8 publications

(3 citation statements)

References 22 publications

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“…In fact, in the present work we show that RBCs from FA patients are significantly modified by a mechanism involving cytoskeleton integrity and we also hypothesize a role for redox imbalance in these changes. An extensive body of evidence has associated the FA phenotype with the occurrence of oxidative stress [4,20]. For instance, it has been shown that FA fibroblasts and leukocytes exhibited lower than normal levels of SOD and/or catalase activities [21].…”

Section: Discussionmentioning

confidence: 99%

Cytoskeleton alterations of erythrocytes from patients with Fanconi's anemia

et al. 2000

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Fanconi's anemia (FA) is a very rare genetically heterogeneous disease which has been hypothesized to be defective in the detoxification of reactive oxygen species. In this work we report the results obtained by morphometric and biochemical analyses on the red blood cells (RBCs) from FA patients. With respect to RBCs from healthy donors the following changes have been detected : (i) a variety of ultrastructural alterations, mainly surface blebbing typical of acanthocytes and stomatocytes; (ii) a significant quantitative increase of these altered forms; (iii) modifications of spectrin cytoskeleton network; (iv) an altered redox balance, e.g. a decreased catalase activity and significant variations in the GSSG/GSH ratio. We hypothesize that remodeling of the redox state occurring in FA patients results in cytoskeleton-associated alterations of red blood cell integrity and function.z 2000 Federation of European Biochemical Societies.

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Section: Discussionmentioning

confidence: 99%

Cytoskeleton alterations of erythrocytes from patients with Fanconi's anemia

et al. 2000

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“…In addition to multiple and variably expressed developmental phenotypes, one observes many phenotypes that can be interpreted as evidence of premature aging, including endocrine abnormalities, gonadal failure, sarcopenia, osteoporosis, increased susceptibility to infectious agents, and progeroid features of skin (Neveling et al 2009). Additional relevant observations have included nuclear aberrations and diminished replication of cultured fibroblasts (Willingale-Theune et al 1989), hypersensitivity to oxidative stress (Liebetrau et al 1997), mitochondrial damage (Pagano et al 2014), and preneoplastic lesions such as leukoplakias of the oral cavity (Grein Cavalcanti et al 2015) and early myelodysplasias (Quentin et al 2011). It has also been described as “a highly penetrant cancer susceptibility syndrome” (Auerbach 2009).…”

Section: Examples Of Segmental Progeroid Syndromesmentioning

confidence: 99%

How Research on Human Progeroid and Antigeroid Syndromes Can Contribute to the Longevity Dividend Initiative

Hisama

Oshima

Martin

2016

Cold Spring Harb Perspect Med

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Although translational applications derived from research on basic mechanisms of aging are likely to enhance healthspans and life spans for most of us (the longevity dividend), there will remain subsets of individuals with special vulnerabilities. Medical genetics is a discipline that describes such “private” patterns of aging and can reveal underlying mechanisms, many of which support genomic instability as a major mechanism of aging. We review examples of three classes of informative disorders: “segmental progeroid syndromes” (those that appear to accelerate multiple features of aging), “unimodal progeroid syndromes” (those that impact on a single disorder of aging) and “unimodal antigeroid syndromes,” variants that provide enhanced protection against specific disorders of aging; we urge our colleagues to expand our meager research efforts on the latter, including ancillary somatic cell genetic approaches.

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“…Oxygen consumption in both FA and control SV40‐transformed fibroblasts was also reduced, an adaptive response to viral immortalization which may help explain resistance of SV40‐transformed FA fibroblasts to molecular oxygen. In a preliminary study Liebetrau et al (1997b ) have examined the mDNA profile in tissues of FA patients, using PCR primer pairs to encompass a 5 kb ‘hot spot’ region for deletion mutations seen in ageing and some mitochondrial diseases. Possibly two of the seven patients tested showed evidence of the common 5 kb deletion, another indication that mDNA is involved in the mechanism of oxidative sensitivity in FA cells.…”

Section: Mitochondria As a Target For MMCmentioning

confidence: 99%