Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P62988 (Ubiquitin)
 4,326 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Over 300 transgenic sugarcane plants representing approx. 200 independent lines producing the human cytokine granulocyte macrophage colony stimulating factor (GM-CSF) were analyzed for recombinant protein accumulation and activity levels. Expression constructs differed in use of the maize polyubiquitin 1, Mubi-1, or the sugarcane polyubiquitin 9, SCubi9, promoters; presence or absence of a C-terminal HDEL tag for ER retention; and presence or absence of a 6X Histidine tag for metal ion affinity purification. Accumulation of GM-CSF protein ranged from undetectable to 0.02% of total soluble protein. No significant difference was observed between the two promoters; however, the ER retention tag was required for higher accumulation levels. Human bone marrow cells (TF-1), which require GM-CSF for cell division, proliferated when growth media was supplemented with transgenic sugarcane extracts. Comparison to purified commercially produced GM-CSF indicated the sugarcane-produced protein had essentially identical activity levels. In a 14-month field trial, accumulation levels remained stable. This is the first report of field production of GM-CSF. During the field trial, no flowering of the trial plants occurred; no pollen or seed was produced. Drying, burning, and burial of the test plants effectively blocked possible routes for the transgenic sugarcane to enter the environment or food supply. Sugarcane may provide a highly secure system for biofactory production of pharmaceutical proteins.
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PMID:Production of biologically active GM-CSF in sugarcane: a secure biofactory. 1602 88

Recent data suggest that ubiquitin has anti-inflammatory properties and therapeutic potential after severe trauma and brain injuries. However, direct evidence for its neuroprotective effects has not yet been provided. We hypothesized that ubiquitin treatment is neuroprotective, and thus reduces brain edema formation and cortical contusion volume after closed traumatic brain injuries. To test this hypothesis, a focal cortical contusion was induced using a controlled cortical impact (CCI) model in Sprague-Dawley rats. Animals (n = 27) were randomized to either 1.5 mg/kg ubiquitin or vehicle (placebo) intravenously within 5 min after CCI. Blood pressure, arterial blood gases (ABG) and intracranial pressure (ICP) were monitored. Ubiquitin serum and cerebrospinal fluid levels were measured by ELISA. Brain water content was quantified gravimetrically after 24 h and cerebral contusion volume was determined in triphenyltetrazolium-chloride stained brains after 7 days. All animals recovered to normal activity. ICP and cerebral perfusion pressures were normal at the end of the observation period. Ubiquitin serum and CSF levels at 24 h and 7 days after CCI were similar in both groups. With ubiquitin brain water content of the injured hemisphere was slightly lower (n = 6/group; 79.97 +/- 0.29% vs. 81.11 +/- 0.52%; p = 0.08). Cortical contusion volume was significantly lower with ubiquitin (n = 7-8/group; 32.88 +/- 2.1 mm(3) vs. 43.96 +/- 4.56 mm(3); p = 0.025). This study shows that ubiquitin treatment after brain injury has direct neuroprotective effects, as demonstrated by improved brain morphology 7 days after brain injury. In connection with its beneficial effects in our previous studies, these data suggest ubiquitin as a promising candidate protein therapeutic for the treatment of brain injuries.
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PMID:Ubiquitin reduces contusion volume after controlled cortical impact injury in rats. 1789 13