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J. Neurochem. (2010) 112, 715–722. Abstract Prion diseases are neurodegenerative disorders characterized by the accumulation of an abnormal isoform of the prion protein PrPSc. Human prion protein fragment, PrP (106–126) (prion protein peptide 106–126), may contain most of the pathological features associated with PrPSc. Hypoxic conditions elicit cellular responses adaptively designed to improve cell survival and have an important role in the process of cell survival. We investigate the effects of hypoxia on PrP (106–126)‐induced apoptosis in the present study. Human neuroblastoma and glioblastoma cells were incubated with varied doses of PrP (106–126) under both normoxic or hypoxic conditions, in order to determine the regulatory effects of hypoxia on PrP (106–126)‐induced apoptosis. The results indicate that hypoxia protects neuronal cells against PrP (106–126)‐induced cell death by activating the Akt signal, which is inactivated by prion proteins, and inhibiting PrP (106–126)‐induced caspase 3 activation. Low oxygen conditions increase the Bcl‐2 protein, which is associated with anti‐apoptotic signals, and recover the PrP (106–126)‐induced reduction in mitochondrial transmembrane potential. This study demonstrates that hypoxia inhibits PrP (106–126)‐induced neuron cell death by regulating Akt and Akt‐related signaling, and it also suggests that prion‐related neuronal damage and disease may be regulated by hypoxia or by hypoxic‐inducing genes.

It has been suggested that plant cell culture is the most suitable system for producing small-to-medium quantities of specialized, expensive, and high-purity proteins. Here, we report that a heterodimeric protein, human interleukin-12 (hIL-12), was expressed and secreted into culture medium in a biologically active form. A transgenic plant expressing hIL-12 was constructed by sexual crossing of plants that expressed each subunit of the protein. From a piece of transgenic plant, callus was induced and cell suspension culture was established. The biological activity and amount of hIL-12 secreted into culture medium were analyzed using bioassays and ELISA. Analysis of cellular localization demonstrated that the protein was secreted into the culture medium together with its intrinsic signal peptide.