Hypoxia induces the activation of the phosphatidylinositol 3-kinase/Akt cell survival pathway in PC12 cells: protective role in apoptosis.

Hypoxia is a common environmental stress that influences signaling pathways and cell function. Several cell types, including neuroendocrine chromaffin cells, have evolved to sense oxygen levels and initiate specific adaptive responses to hypoxia. Here we report that under hypoxic conditions, rat pheochromocytoma PC12 cells are resistant to apoptosis induced by serum withdrawal and chemotherapy treatment. This effect is also observed after treatment with deferoxamine, a compound that mimics many of the effects of hypoxia. The hypoxia-dependent protection from apoptosis correlates with activation of the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which is detected after 3-4 h of hypoxic or deferoxamine treatment and is sustained while hypoxic conditions are maintained. Hypoxia-induced Akt activation can be prevented by treatment with cycloheximide or actinomycin D, suggesting that de novo protein synthesis is required. Finally, inhibition of PI3K impairs both the protection against apoptosis and the activation of Akt in response to hypoxia, suggesting a functional link between these two phenomena. Thus, reduced oxygen tension regulates apoptosis in PC12 cells through activation of the PI3K/Akt survival pathway.

Phylogeny and rapid northern and southern hemisphere speciation of goldfinches during the Miocene and Pliocene epochs.

Mitochondrial cytochrome b (cyt b) from 25 out of 31 extant goldfinches, siskins, greenfinches and redpolls (genus Carduelis) has been sequenced from living samples taken around the world, specimens have also been photographed. Phylogenetic analysis consistently gave the same groups of birds, and this grouping was generally related to geographical proximity. It has been supposed that Pleistocene glaciations played a crucial role in the origin of extant diversity and distribution of Northern Hemisphere vertebrates. Molecular comparison of most extant songbird species belonging to the genus Carduelis does not support this assertion. The fossil record of chicken and pheasant divergence time has been used to calibrate the molecular clock; cyt b DNA dendrograms suggest that speciation in Carduelinae birds occurred during the Miocene and Pliocene Epochs (9-2 million years ago) in both the Northern and Southern Hemispheres. Only about 4% average amount of nucleotide substitution per lineage is found between the most distant Carduelis species; this suggests a remarkably rapid radiation when compared with the radiation of other passerine songbird genera. In addition, a continuum of small songbird speciation may be found during the Miocene Epoch in parallel with speciation of other orders (i.e. Galliformes, chicken/pheasant). Pleistocene glaciations may have been important in subspeciation (i.e. Eastern European grey-headed goldfinches/Western European black-headed goldfinches) and also in ice-induced vicariance (isolation) (i.e. siskin in Western Europe vs. siskin in Far East Asia) around the world. European isolated Serinus citrinella (citril finch) is not a canary, but a true goldfinch. South American siskins have quickly radiated in the last 4 million years coinciding with the emergence of the Isthmus of Panama; probably, a North American siskin related to C. notata invaded a suitable and varied biotope (the South American island) for Carduelis birds. North American goldfinches may be renamed as siskins, because they have a distant genetic relationship with European goldfinches. Genus Acanthis could be dropped, and thus redpolls should be separated from twite and linnet, the latter (Europeans) probably being related to American goldfinches. Also, reproductive barriers are observed between closely related species and not between other more distant ones. Finally, a tentative classification for genus Carduelis species is suggested.

Description of two Mhc-C-related sequences in the New World monkey Saguinus oedipus.

Two new Mhc class I partial exon 1, intron 1, exon 2, intron 2 and partial exon 3 DNA sequences from the New World monkey Saguinus oedipus (Saoe) are described. These two sequences show certain Mhc-C sequence-specific changes. The only difference between these two new sequences is a productive substitution at position 152 [GCG (Ala)-->GAG (Glu)]. This change occurs in a position which in Mhc classical class I molecules affects the interaction between the peptide and the T-cell receptor. A dendrogram with Mhc sequences from different loci and different species was constructed, which clearly shows that these two new sequences cluster closer to Mhc-C sequences than to others. These data suggest that the new sequences may be related to the Mhc-C locus, and they have been named Mhc-Saoe-CR*01 and -CR*02. However, they share only a few of the conserved residues (from gorilla to human) of Mhc-C sequences, which suggests that the relationships with an ancestor of the Mhc-C lineage are very distant or that these two sequences are products of convergent evolution to perform a C locus related function. Furthermore, in the fragment of DNA sequenced, there is a loss of two invariant residues conserved in antigen-presenting molecules from reptiles to humans; thus, it is unlikely that these two Mhc-C-like sequences have an antigen-presenting function, or even that they are two alleles of a pseudogene; however, the G + C percentage (86.1%) at the third base of codons approaches that of an expressed gene in Saoe. It is concluded that Mhc molecules with C-locus characteristics existed in primates 50 million years ago and that this does not support a more recent origin of Mhc-C genes.