Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

PDC-109, a protein of unknown function, is a major component of bovine seminal plasma. Using a computer program designed to detect evolutionary relationships between proteins, I find that the PDC-109 protein is similar to the gelatin-binding domain of bovine fibronectin and part of a kringle domain of human tissue-type plasminogen activator (t-PA). The computer-based comparison of the amino acid sequence of PDC-109 with that of the gelatin-binding domain of fibronectin and part of the second kringle domain of t-PA yields scores that are 15.5 standard deviations and 7.8 standard deviations higher, respectively, than were obtained with a comparison of randomized sequences of these proteins. The probability (p) of getting these scores by chance is less than 10(-50) and 3 X 10(-15), respectively. The similarity between the amino acid sequences of PDC-109 and the gelatin-binding domain in fibronectin and the kringle of t-PA suggests some approaches for identifying the functions of PDC-109. Both t-PA and the gelatin-binding domain of fibronectin have adhesive functions, and the gelatin-binding domain promotes viral transformation of fibroblasts in culture. These functions may be associated with the PDC-109 protein.
 ...
PMID:The PDC-109 protein from bovine seminal plasma is similar to the gelatin-binding domain of bovine fibronectin and a kringle domain of human tissue-type plasminogen activator. 404 Jul 57

Peroxynitrite (ONOO-) and high mobility group box 1 protein (HMGB1) are important cytotoxic factors contributing to cerebral ischemia-reperfusion injury. However, the roles of ONOO- in mediating HMGB1 expression and its impacts on hemorrhagic transformation (HT) in ischemic brain injury with delayed t-PA treatment remain unclear. In the present study, we tested the hypothesis that ONOO- could directly mediate the activation and release of HMGB1 in ischemic brains with delayed t-PA treatment. With clinical studies, we found that plasma nitrotyrosine (NT, a surrogate marker of ONOO-) was positively correlated with HMGB1 level in acute ischemic stroke patients. Hemorrhagic transformation and t-PA-treated ischemic stroke patients had increased levels of nitrotyrosine and HMGB1 in plasma. In animal experiments, we found that FeTmPyP, a representative ONOO- decomposition catalyst (PDC), significantly reduced the expression of HMGB1 and its receptor TLR2, and inhibited MMP-9 activation, preserved collagen IV and tight junction claudin-5 in ischemic rat brains with delayed t-PA treatment. ONOO- donor SIN-1 directly induced expression of HMGB1 and its receptor TLR2 in naive rat brains in vivo and induced HMGB1 in brain microvascular endothelial b.End3 cells in vitro. Those results suggest that ONOO- could activate HMGB1/TLR2/MMP-9 signaling. We then addressed whether glycyrrhizin, a natural HMGB1 inhibitor, could inhibit ONOO- production and the antioxidant properties of glycyrrhizin contribute to the inhibition of HMGB1 and the neuroprotective effects on attenuating hemorrhagic transformation in ischemic stroke with delayed t-PA treatment. Glycyrrhizin treatment downregulated the expressions of NADPH oxidase p47 phox and p67 phox and iNOS, inhibited superoxide and ONOO- production, reduced the expression of HMGB1, TLR2, MMP-9, preserved type IV collagen and claudin-5 in ischemic brains. Furthermore, glycyrrhizin significantly decreased the mortality rate, attenuated hemorrhagic transformation, brain swelling, blood-brain barrier damage, neuronal apoptosis, and improved neurological outcomes in the ischemic stroke rat model with delayed t-PA treatment. In conclusion, peroxynitrite-mediated HMGB1/TLR2 signaling contributes to hemorrhagic transformation, and glycyrrhizin could be a potential adjuvant therapy to attenuate hemorrhagic transformation, possibly through inhibiting the ONOO-/HMGB1/TLR2 signaling cascades.
 ...
PMID:Glycyrrhizin Prevents Hemorrhagic Transformation and Improves Neurological Outcome in Ischemic Stroke with Delayed Thrombolysis Through Targeting Peroxynitrite-Mediated HMGB1 Signaling. 3187 39