Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024312 (lymphopenia)
 4,859 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatic stem cell (SSC) dysfunction is typical for different progeroid phenotypes in mice with genomic DNA repair defects. MtDNA mutagenesis in mice with defective Polg exonuclease activity also leads to progeroid symptoms, by an unknown mechanism. We found that Polg-Mutator mice had neural (NSC) and hematopoietic progenitor (HPC) dysfunction already from embryogenesis. NSC self-renewal was decreased in vitro, and quiescent NSC amounts were reduced in vivo. HPCs showed abnormal lineage differentiation leading to anemia and lymphopenia. N-acetyl-L-cysteine treatment rescued both NSC and HPC abnormalities, suggesting that subtle ROS/redox changes, induced by mtDNA mutagenesis, modulate SSC function. Our results show that mtDNA mutagenesis affected SSC function early but manifested as respiratory chain deficiency in nondividing tissues in old age. Deletor mice, having mtDNA deletions in postmitotic cells and no progeria, had normal SSCs. We propose that SSC compartment is sensitive to mtDNA mutagenesis, and that mitochondrial dysfunction in SSCs can underlie progeroid manifestations.
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PMID:Somatic progenitor cell vulnerability to mitochondrial DNA mutagenesis underlies progeroid phenotypes in Polg mutator mice. 2222 68

Toxic and carcinogenic effects of nickel compounds are suggested to result from nickel-mediated oxidative damage to macromolecules and/or inhibition of cellular antioxidant defenses. We investigated the effects of waterborne Ni(2+) (10, 25 and 50 mg/L) on the blood and blood-producing tissues (kidney and spleen) of goldfish to identify relationships between Ni accumulation and oxidative stress. Whereas the main hematological parameters (total hemoglobin and hematocrit) were unaffected, Ni(2+) exposure had substantial influence on goldfish immune system, causing lymphopenia. Ni accumulation increased renal iron content (by 49-78%) and resulted in elevated lipid peroxide (by 29%) and protein carbonyl content (by 274-278%), accompanied by suppression of the activities of superoxide dismutase (by 50-53%), glutathione peroxidase (15-45%), glutathione reductase (31-37%) and glucose-6-phosphate dehydrogenase (20-44%), indicating development of oxidative stress in kidney. In contrast to kidney, in spleen the activation of glutathione peroxidase (by 34-118%), glutathione-S-transferase (by 41-216%) and glutathione reductase (by 47%), as well as constant levels of low molecular mass thiols and metals together with enhanced activity of glucose-6-phosphate dehydrogenase (by 41-94%) speaks for a powerful antioxidant potential that counteracts Ni-induced ROS production. Further, as Ni accumulation in this organ was negligible, Ni-toxicity in spleen may be minimized by efficient exclusion of this otherwise toxic metal.
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PMID:Tissue specificity in nickel uptake and induction of oxidative stress in kidney and spleen of goldfish Carassius auratus, exposed to waterborne nickel. 2253 63