RESUMEN
The general idea of regenerative medicine is to fix or replace tissues or organs with live and patient-specific implants. Pluripotent stem cells are capable of indefinite self-renewal and differentiation into all cell types of the body. An easily accessible source of induced pluripotent stem cells (iPSCs) may allow obtaining and culturing tissues in vitro. Many approaches in the methods leading to obtain iPSCs have been tested in order to limit immunogenicity and tumorigenesis, and to increase efficiency. One of the approaches causing pluripotency is usage of small molecule compounds. It would be of great importance to assess their specific properties and reveal their new capacity to induce pluripotent stem cells and to improve reprogramming efficiency. Identification of the epigenetic changes during cellular reprogramming will extend our understanding of stem cell biology and many therapeutic applications. In this paper we discuss mainly the nucleotide derivatives, already proven or for now only putative inducers of the cells' pluripotency, that modulate the epigenetic status of the cell.
Asunto(s)
Reprogramación Celular , Citidina/análogos & derivados , Citidina/farmacología , Epigénesis Genética/efectos de los fármacos , Células Madre Pluripotentes Inducidas/fisiología , Animales , Humanos , Metiltransferasas/antagonistas & inhibidores , Medicina RegenerativaRESUMEN
Arabidopsis thaliana proteome contains 667 proteases; some tens of them are chloroplast-targeted proteins, encoded by genes orthologous to the ones coding for bacterial proteolytic enzymes. It is thought that chloroplast proteases are involved in chloroplasts' proteins turnover and quality control (maturation of nucleus-encoded proteins and removal of nonfunctional ones). Some ATP-dependent chloroplast proteases belonging to FtsH family (especially FtsH2 and FtsH5) are considered to be involved in numerous aspects of chloroplast and whole plant maintenance under non-stressing as well as stressing conditions. This notion is supported by severe phenotype appearance of mutants deficient in these proteases. In contrast to seemingly high physiological importance of chloroplast members of FtsH protease family, only a few individual proteins have been identified so far as their physiological targets (i.e. Lhcb1, Lhcb3, PsbA and Rieske protein). Our knowledge regarding structure and molecular mechanisms of these enzymes' action is limited when compared with what is known about FtsHs of bacterial origin. Equally limited is the knowledge about ATP-dependent Lon4 protease being the single known chloroplast-targeted ortholog of Lon protease of Escherichia coli.
Asunto(s)
Proteasas ATP-Dependientes/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/enzimología , Proteínas de la Membrana/metabolismo , Proteasa La/metabolismo , Proteasas ATP-Dependientes/química , Proteínas de Arabidopsis/química , Escherichia coli/enzimología , Proteínas de la Membrana/química , Metaloproteasas/química , Metaloproteasas/metabolismo , MutaciónRESUMEN
For some chloroplast proteases ATP binding and hydrolysis is not necessary for their catalytic activity, most probably because even strongly unfolded substrates may penetrate their catalytic chamber. Deg1, 2, 5 and 8 are the best known of Arabidopsis thaliana ATP- independent chloroplast proteases, encoded by orthologues of genes coding for DegP, DegQ and DegS proteases of Escherichia coli. Current awareness in the area of structure and functions of chloroplast Degs is much more limited vs the one about their bacterial counterparts. Deg5 and Deg8 form a catalytic heterododecamer which is loosely attached to luminal side of thylakoid membrane. The complex catalyses--supported by Deg1 and one of FtsH proteases--the degradation of PsbA damaged due to plant exposition to elevated irradiance and thus these protease are of key importance for the plants' sensitivity to photoinhibition. Deg2 role in the disposal of damaged PsbA has not been elucidated. Recombinant Deg1 may degrade PsbO and plastocyanin in vitro but it is not clear whether this reaction is performed in vivo as well.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Cloroplastos/enzimología , Péptido Hidrolasas/metabolismo , Proteínas de Arabidopsis/química , Serina Endopeptidasas/química , Serina Endopeptidasas/metabolismo , Especificidad por SustratoRESUMEN
Proteins involved in apoptosis are still a matter of debate. Therefore, we decided to check the effect of the presence of VDAC (voltage dependent anion selective channel) on viability of Saccharomyces cerevisiae cells following their exposure to H(2)O(2) that is known to induce apoptosis both in S. cerevisiae and in mammalian cells. Mitochondria of S. cerevisiae contain only one channel-forming VDAC isoform (VDAC1), which simplifies studies on the channel. Using S. cerevisiae mutant depleted of VDAC1 (termed here VDAC) and the isogenic wild type, we have shown that VDAC is important for protection of S. cerevisiae cells against H(2)O(2) treatment, particularly in exponential growth phase that is known to be more affected by H(2)O(2). The increased viability of H(2)O(2) pretreated exponentially growing cells containing VDAC was accompanied by clear changes of the cytosol redox state and was potentiated by minocycline, an antibiotic of the tetracycline family that displays cytoprotective potency. The protective effect of minocycline also coincided with distinct changes of cytosol redox state. Thus, we conclude that the ability to change the cytosol redox state following exposure to H(2)O(2) or/and minocycline appears to be an intrinsic feature of exponentially growing cells (young cells) containing VDAC. Moreover, the ability seems to be crucial for both cell viability and protective effect of minocycline.