Regulation of mitogen-activated protein kinases in cardiac myocytes through the small G protein Rac1.

Small guanine nucleotide-binding proteins of the Ras and Rho (Rac, Cdc42, and Rho) families have been implicated in cardiac myocyte hypertrophy, and this may involve the extracellular signal-related kinase (ERK), c-Jun N-terminal kinase (JNK), and/or p38 mitogen-activated protein kinase (MAPK) cascades. In other systems, Rac and Cdc42 have been particularly implicated in the activation of JNKs and p38-MAPKs. We examined the activation of Rho family small G proteins and the regulation of MAPKs through Rac1 in cardiac myocytes. Endothelin 1 and phenylephrine (both hypertrophic agonists) induced rapid activation of endogenous Rac1, and endothelin 1 also promoted significant activation of RhoA. Toxin B (which inactivates Rho family proteins) attenuated the activation of JNKs by hyperosmotic shock or endothelin 1 but had no effect on p38-MAPK activation. Toxin B also inhibited the activation of the ERK cascade by these stimuli. In transfection experiments, dominant-negative N17Rac1 inhibited activation of ERK by endothelin 1, whereas activated V12Rac1 cooperated with c-Raf to activate ERK. Rac1 may stimulate the ERK cascade either by promoting the phosphorylation of c-Raf or by increasing MEK1 and/or -2 association with c-Raf to facilitate MEK1 and/or -2 activation. In cardiac myocytes, toxin B attenuated c-Raf(Ser-338) phosphorylation (50 to 70% inhibition), but this had no effect on c-Raf activity. However, toxin B decreased both the association of MEK1 and/or -2 with c-Raf and c-Raf-associated ERK-activating activity. V12Rac1 cooperated with c-Raf to increase expression of atrial natriuretic factor (ANF), whereas N17Rac1 inhibited endothelin 1-stimulated ANF expression, indicating that the synergy between Rac1 and c-Raf is potentially physiologically important. We conclude that activation of Rac1 by hypertrophic stimuli contributes to the hypertrophic response by modulating the ERK and/or possibly the JNK (but not the p38-MAPK) cascades.

Variability and trends in Laptev Sea ice outflow between 1992-2011

Variability and trends in seasonal and interannual ice area export out of the Laptev Sea between 1992 and 2011 are investigated using satellite-based sea ice drift and concentration data. We found an average total winter (Octo- ber to May) ice area transport across the northern and east- ern Laptev Sea boundaries (NB and EB) of 3.48 × 10 5 km 2 . The average transport across the NB (2.87 × 10 5 km 2 ) is thereby higher than across the EB (0.61 × 10 5 km 2 ), with a less pronounced seasonal cycle. The total Laptev Sea ice area flux significantly increased over the last decades (0.85 × 10 5 km 2 decade − 1 , p> 0 . 95), dominated by increas- ing export through the EB (0.55 × 10 5 km 2 decade − 1 , p> 0 . 90), while the increase in export across the NB is smaller (0.3 × 10 5 km 2 decade − 1 ) and statistically not significant. The strong coupling between across-boundary SLP gradient and ice drift velocity indicates that monthly variations in ice area flux are primarily controlled by changes in geostrophic wind velocities, although the Laptev Sea ice circulation shows no clear relationship with large-scale atmospheric in- dices. Also there is no evidence of increasing wind velocities that could explain the overall positive trends in ice export. The increased transport rates are rather the consequence of a changing ice cover such as thinning and/or a decrease in con- centration. The use of a back-propagation method revealed that most of the ice that is incorporated into the Transpolar Drift is formed during freeze-up and originates from the cen- tral and western part of the Laptev Sea, while the exchange with the East Siberian Sea is dominated by ice coming from the central and southeastern Laptev Sea. Furthermore, our re- sults imply that years of high ice export in late winter (Febru- ary to May) have a thinning effect on the ice cover, which in turn preconditions the occurence of negative sea ice extent anomalies in summer.