To understand these phenomena,
we examined the effects of the P90A and A92E changes in the HIV-1 CA protein on the stability of capsid complexes assembled in vitro and on capsid disassembly in the cytosol of virus-exposed target cells. The A92E change impaired CA-CA interactions in vitro and decreased the amount of particulate capsids in the cytosol of HeLa target cells. Reducing the binding of CypA to the A92E mutant capsid, either by Cs treatment or by an additional P90A change in the CA protein, increased the amount of particulate capsids and viral infectivity in HeLa cells. In contrast, reduction of the binding of CypA to HIV-1 capsids in Jurkat T lymphocytes resulted in a decrease in the amount of particulate capsids
and infectivity. Thus, depending on the capsid and the target cell, CypA-CA binding either stabilized or destabilized the capsid, indicating that CypA modulates HIV-1 SC79 molecular weight capsid disassembly. In both cell types examined, decreased stability of the capsid was associated with a decrease Omipalisib cost in the efficiency of HIV-1 infection.”
“The indirubins long have been used in Chinese medicine for treatment of myelocytic leukemia. Among the many more recently described biological activities of the indirubins, attention has been directed toward the ability of these compounds to inhibit GSK-3 and CDKs, kinases implicated in neurodegenerative conditions. Little information is available on effects of indirubins on chemically-induced neurodegeneration. Here we examined the influence of three indirubins on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- and kainic acid (KA)-induced neurotoxicity in the mouse. The three indirubins examined were 6-bromoindirubin-3′-oxime (6BIO), 5-bromoindirubin-3′-oxime (5BIO) and 5-amino-6-bromoindirubin
(5A6BI). The first two derivatives were previously described indirubins with low nanomolar inhibitory activity against GSK-3 and CDKs. The third compound was synthesized by the dimerization of 5-amino-6-bromoisatin with 3-acetoxyindol. The synthesis of the key compound 5-amino-6-bromoisatin was based on the bromination of the ketal of 5-amino-isatin. All indirubins examined decreased various measures associated with dopaminergic neurotransmission in striatum. These effects occurred alone or over and above the Methocarbamol decrements seen following administration of the dopaminergic neurotoxicant, MPTP. Striatal serotonin and serotonin turnover were decreased by the indirubins in MPTP-treated mice. None of these striatal effects of the indirubins alone were associated with evidence of astrogliosis, an indicator of underlying neuropathology, nor did they potentiate the astrogliosis accompanying administration of MPTP. In general, the indirubins reduced KA-associated mortality and striatal but not hippocampal astrogliosis due to this toxicant. The data suggest that indirubins affect striatal biogenic amine levels and turnover in intact mice.