Sandbox Reserved 192: Difference between revisions
| Line 22: | Line 22: | ||
=='''Medical Implications'''== | =='''Medical Implications'''== | ||
A recent study by Patutina et al. (2011) revealed that tumor propagation is associated with an imbalance in nucleic acid metabolism. In the blood plasma of patients, there were increased levels of circulating nucleic acids and decreased nuclease activity. The abnormally high levels of circulating nucleic acids | A recent study by Patutina et al. (2011) revealed that tumor propagation is associated with an imbalance in nucleic acid metabolism. In the blood plasma of patients, there were increased levels of circulating nucleic acids and decreased nuclease activity. The abnormally high levels of circulating nucleic acids were associated with the increased expression and secretion of tumor-derived miRNA and DNA. With increased expression, the tumor progresses and the patient has a bad prognosis. | ||
RNase A and DNase I inhibit metastasis [http://en.wikipedia.org/wiki/Metastasis] by catalyzing metastasis pathomorphosis which is apoptosis, necrosis [http://en.wikipedia.org/wiki/Necrosis] and destruction of oncocytes [http://en.wikipedia.org/wiki/Oncocyte]. This capability retards the primary tumor growth by 30-40%. The tumor bearing mice received doses of RNase A, DNase I or a mixture of the two and the most significant effect observed was in the mice treated with both enzymes simultaneously. Thus the simultaneous administration of RNase A and DNase I led to an anti-metastatic effect and resulted in an almost complete absence in the metastasis of the tumor. Further observations suggest that RNase A and DNase I are toxic at high levels. So for effective treatment, ultra low doses are required to stay below the level of toxicity. | RNase A and DNase I inhibit metastasis [http://en.wikipedia.org/wiki/Metastasis] by catalyzing metastasis pathomorphosis which is apoptosis, necrosis [http://en.wikipedia.org/wiki/Necrosis] and destruction of oncocytes [http://en.wikipedia.org/wiki/Oncocyte]. This capability retards the primary tumor growth by 30-40%. The tumor bearing mice received doses of RNase A, DNase I or a mixture of the two and the most significant effect observed was in the mice treated with both enzymes simultaneously. Thus the simultaneous administration of RNase A and DNase I led to an anti-metastatic effect and resulted in an almost complete absence in the metastasis of the tumor. Further observations suggest that RNase A and DNase I are toxic at high levels. So for effective treatment, ultra low doses are required to stay below the level of toxicity. | ||
Another member in the ribonuclease family and structural homologue to bovine RNase A is frog onconase [http://en.wikipedia.org/wiki/Onconase] or ONC. ONC is found in oocytes [http://en.wikipedia.org/wiki/Oocytes] and early embryos of northern leopard frogs. The frog ribonuclease variant shows both cytostatic (cell growth suppression) and cytotoxic (prevents cell divisions) characteristics when it interacts with tumor cells. According to Leland et al. (2001), no side effects have been determined for ONC. Leland et al. (2001) looked to determine the interactions that control the folding of ONC in order to develop effective mimics of ONC. In order to determine the interactions that controlled folding, the regeneration of RNase A was studied. Although RNase A and ONC were structurally very similar, there were significant differences in their folding pathways. While ONC forms a stable disulfide intermediate, RNase A does not. ONC was also found to be missing a disulfide bond that RNase A possesses. In the case of both enzymes, entropy is lost in the formation of the disulfide bonds, but folding may be driven by enthalpically favorable interactions of the side chains. Further experiments are being done to identify intramolecular interactions that account for the increased rate and formation of the structured intermediate in ONC. | Another member in the ribonuclease family and structural homologue to bovine RNase A is frog onconase [http://en.wikipedia.org/wiki/Onconase] or ONC. ONC is found in oocytes [http://en.wikipedia.org/wiki/Oocytes] and early embryos of northern leopard frogs. The frog ribonuclease variant shows both cytostatic (cell growth suppression) and cytotoxic (prevents cell divisions) characteristics when it interacts with tumor cells. According to Leland et al. (2001), no side effects have been determined for ONC. Leland et al. (2001) looked to determine the interactions that control the folding of ONC in order to develop effective mimics of ONC. In order to determine the interactions that controlled folding, the regeneration of RNase A was studied. Although RNase A and ONC were structurally very similar, there were significant differences in their folding pathways. While ONC forms a stable disulfide intermediate, RNase A does not. ONC was also found to be missing a disulfide bond that RNase A possesses. In the case of both enzymes, entropy is lost in the formation of the disulfide bonds, but folding may be driven by enthalpically favorable interactions of the side chains. Further experiments are being done to identify intramolecular interactions that account for the increased rate and formation of the structured intermediate in ONC. | ||
<Structure load='7RSA' size='300' frame='true' align='left' caption='Insert caption here' scene='Sandbox_Reserved_192/Second_rnase_structure_blue/1' /> | <Structure load='7RSA' size='300' frame='true' align='left' caption='Insert caption here' scene='Sandbox_Reserved_192/Second_rnase_structure_blue/1' /> | ||