71 research outputs found
AVE0991, a Nonpeptide Compound, Attenuates Angiotensin II-Induced Vascular Smooth Muscle Cell Proliferation via Induction of Heme Oxygenase-1 and Downregulation of p-38 MAPK Phosphorylation
The nonpeptide AVE0991 is an agonist of the angiotensin-(1–7) (Ang-(1–7)) Mas receptor and is expected to be a putative new drug for treatment of cardiovascular disease. However, the mechanisms involved in the antiproliferative effects of AVE0991 are not fully understood. We saw that the compound attenuated proliferation in an angiotensin II-induced rat vascular smooth muscle cells (VSMC) proliferation model. Moreover, treatment with AVE0991 (10−5 mol/L or 10−7 mol/L) significantly attenuated reactive oxygen species (ROS) production, phosphorylation of p38 MAPK, and dose-dependently (10−8 to 10−5 mol/L) inhibited Ang II-induced VSMC proliferation. Meanwhile, heme oxygenase-1 (HO-1) expression increased in the AVE0991 + Ang II group (10−5 mol/L or 10−6 mol/L). However, the beneficial effects of AVE0991 were completely abolished when the VSMC were pretreated with A-779 (10−6 mol/L). Furthermore, treatment with the HO-1 inhibitor ZnPPIX attenuated the inhibitory effect of AVE0991 on Ang II-induced p38MAPK phosphorylation. These results suggest that AVE0991 attenuates Ang II-induced VSMC proliferation in a dose-dependent fashion and that this effect is associated with the Mas/HO-1/p38 MAPK signaling pathway
Immunolocalization of dually phosphorylated MAPKs in dividing root meristem cells of Vicia faba, Pisum sativum, Lupinus luteus and Lycopersicon esculentum
Key message In plants, phosphorylated MAPKs display
constitutive nuclear localization; however, not all
studied plant species show co-localization of activated
MAPKs to mitotic microtubules.
Abstract The mitogen-activated protein kinase (MAPK)
signaling pathway is involved not only in the cellular
response to biotic and abiotic stress but also in the regulation
of cell cycle and plant development. The role of
MAPKs in the formation of a mitotic spindle has been
widely studied and the MAPK signaling pathway was
found to be indispensable for the unperturbed course of cell
division. Here we show cellular localization of activated
MAPKs (dually phosphorylated at their TXY motifs) in
both interphase and mitotic root meristem cells of Lupinus
luteus, Pisum sativum, Vicia faba (Fabaceae) and Lycopersicon esculentum (Solanaceae). Nuclear localization
of activated MAPKs has been found in all species. Colocalization
of these kinases to mitotic microtubules was
most evident in L. esculentum, while only about 50 % of
mitotic cells in the root meristems of P. sativum and V.
faba displayed activated MAPKs localized to microtubules
during mitosis. Unexpectedly, no evident immunofluorescence
signals at spindle microtubules and phragmoplast
were noted in L. luteus. Considering immunocytochemical
analyses and studies on the impact of FR180204 (an
inhibitor of animal ERK1/2) on mitotic cells, we hypothesize
that MAPKs may not play prominent role in the
regulation of microtubule dynamics in all plant species
Identification of new members of the MAPK gene family in plants shows diverse conserved domains and novel activation loop variants
International Journal of Pharma and Bio Sciences REVIEW ARTICLE BIOCHEMISTRY P38
Ischaemic heart disease remains, and is likely to continue to be, the leading life threatening disease around the world. Signaling pathways have become more interesting as novel therapeutic targets in ischaemic heart disease. However, one needs to be very careful in picking the therapeutic target as one signaling molecule can activate and also cross-talk with other kinases. The activation of the p38-MAPK during myocardial ischaemia aggravates lethal injury. Recent evidences suggested the mechanism of p38-MAPK activation may differ by circumstances. Determining the precise mechanisms is crucial since it may allow prevention of the detrimental, but not the beneficial, and lead to the identification of the relevant downstream signals. Therefore, p38 MAPK may be a viable clinical target and form the basis of future studies designed to further dissect the signaling pathways and discover the downstream substrates will become hopes as a new frontier of therapeutic approach in ischaemic heart diseases. This article can be downloaded from www.ijpbs.ne
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