SB 202190 - Helps In The Study Of The Role Of P38 And Beta - MAPK

By [http://ezinearticles.com/?expert=Kate_Rabia]Kate Rabia
INTRODUCTION
SB 202190 is a potent inhibitor of p38 MAPK and hence regulates the synthesis of inflammatory cytokines. It also stimulates the process of apoptosis in cancerous cells. This small molecule competed with ATP and binds at the ATP binding site. In this way it affects the catalytic activity of the kinase enzyme.
SB 202190: HELPS IN THE IDENTIFICATION OF THE P38Β MAPK
The extracellular signals are transduced into various cellular responses by various MAPK cascades within the eukaryotic organisms. Within human beings there are 4 subgroups of MAP kinases which are JNK (SAPK), ERK5, ERK and p38. SB 202190 helped in the identification of new MAPK that is p38β MAPK, which is a protein made up of 372 amino acids. It is very similar to p38, in its mode of action and contains a short motif made up of amino acids, Thre-Gly-Tyr. This short motif serves as a dual phosphorylation moiety which is very essential for the kinase activity. p38β also gets stimulated by external stress and inflammatory cytokines. The upstream enzyme for p38β is MKK6 whereas p38 MAPK gets equally activated by the upstream enzymes MKK3, MKK6 and MKK4. The downstream substrate for p38β was found to be ATF2. SB 202190 belongs to the group of pyridinyl- imidazoles which inhibits the synthesis of IL-1 and TNF from human monocytes. The p38 and p38β MAPK are close homologues and are termed as CSBPs. SB 202190 inhibited the kinase activity of CSBPs hence inhibiting the production of cytokines.
SB 202190: REGULATES LPS INDUCED MRNA IN MONOCYTES
Previous research studies have shown that p38 MAPK blocks the synthesis of IL-1 and TNF -alpha at the level of translation within monocytes. SB202190 blocks the LPS induced gene expression and is also a selective inhibitor of p38. The genes which are stimulated by LPS (neuroleukin, gene 15 which is introduced by interferon, early gene-1 which is induced by radiation, IL-1b, A20 and superoxide dismutase) were suppressed to significant levels by SB202190. This inhibitor blocked upto 50% of the expression of these genes at a concentration of 41 to 123 nM. SB202190 also blocked the IL-8 mRNA levels, which was induced by both LPS and TNF- alpha. These studies showed that p38 was responsible for the expression of all the genes which were stimulated by TNF- alpha and LPS. As SB202190 is a specific inhibitor of p38 it was potent enough to suppress the LPS-induced gene expression within monocytes.
SB 202190: ROLE IN APOPTOSIS
SB 202190 has been found to be very specific in its action against p38β and p38α isoforms of p38 MAPK. It was potent enough to induce apoptosis in cancer cells by causing condensation of the nucleus and fragmentation of DNA within the neucleosomes. It also stimulated the activity of caspases whose action was similar to CPP32. This effect of SB202190 on apoptosis was completely blocked by proteasomal inhibitor or by the bcl-2 expression. SB202190 also stimulates the apoptosis which is induced by the ligation of Fas(APO-1) or radiation by ultra violet rays. However these effects on apoptosis were reversed by the expression of p38β. This also shows that p38β and p38α have different functions in the process of induction of apoptosis.
CONCLUSION
To summarize, SB202190 is a potent inhibitor of different isoforms of p38 MAPK. It had helped the scientists to study the physiological role of p38 MAPK. It plays a significant role in inducing apoptosis within the cancerous cells.
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Article Source: [http://EzineArticles.com/?SB-202190---Helps-In-The-Study-Of-The-Role-Of-P38-And-Beta---MAPK&id=6653217] SB 202190 - Helps In The Study Of The Role Of P38 And Beta - MAPK