P21-PARP-1 pathway is involved in cigarette smoke-induced lung DNA damage and cellular senescence

Persistent DNA damage triggers cellular senescence, which may play an important role in the pathogenesis of cigarette smoke (CS)-induced lung diseases. Both p21(CDKN1A) (p21) and poly(ADP-ribose) polymerase-1 (PARP-1) are involved in DNA damage and repair. However, the role of p21-PARP-1 axis in regulating CS-induced lung DNA damage and cellular senescence remains unknown. We hypothesized that CS causes DNA damage and cellular senescence through a p21-PARP-1 axis. To test this hypothesis, we determined the levels of γH2AX (a marker for DNA double-strand breaks) as well as non-homologous end joining proteins (Ku70 and Ku80) in lungs of mice exposed to CS. We found that the level of γH2AX was increased, whereas the level of Ku70 was reduced in lungs of CS-exposed mice. Furthermore, p21 deletion reduced the level of γH2AX, but augmented the levels of Ku70, Ku80, and PAR in lungs by CS. Administration of PARP-1 inhibitor 3-aminobenzamide increased CS-induced DNA damage, but lowered the levels of Ku70 and Ku80, in lungs of p21 knockout mice. Moreover, 3-aminobenzamide increased senescence-associated β-galactosidase activity, but decreased the expression of proliferating cell nuclear antigen in mouse lungs in response to CS. Interestingly, 3-aminobenzamide treatment had no effect on neutrophil influx into bronchoalveolar lavage fluid by CS. These results demonstrate that the p21-PARP-1 pathway is involved in CS-induced DNA damage and cellular senescence

Spatiotemporal Evolution of Calophaca (Fabaceae) Reveals Multiple Dispersals in Central Asian Mountains

BackgroundThe Central Asian flora plays a significant role in Eurasia and the Northern Hemisphere. Calophaca, a member of this flora, includes eight currently recognized species, and is centered in Central Asia, with some taxa extending into adjacent areas. A phylogenetic analysis of the genus utilizing nuclear ribosomal ITS and plastid trnS-trnG and rbcL sequences was carried out in order to confirm its taxonomic status and reconstruct its evolutionary history.Methodology/principal findingWe employed BEAST Bayesian inference for dating, and S-DIVA and BBM for ancestral area reconstruction, to study its spatiotemporal evolution. Our results show that Calophacais monophyletic and nested within Caragana. The divergence time of Calophaca is estimated at ca. 8.0 Ma, most likely driven by global cooling and aridification, influenced by rapid uplift of the Qinghai Tibet Plateau margins.Conclusions/significanceAccording to ancestral area reconstructions, the genus most likely originated in the Pamir Mountains, a global biodiversity hotspot and hypothesized Tertiary refugium of many Central Asian plant lineages. Dispersals from this location are inferred to the western Tianshan Mountains, then northward to the Tarbagatai Range, eastward to East Asia, and westward to the Caucasus, Russia, and Europe. The spatiotemporal evolution of Calophaca provides a case contributing to an understanding of the flora and biodiversity of the Central Asian mountains and adjacent regions