AMPK Causes Cell Cycle Arrest in LKB1-deficient Cells via Activation of CAMKK2

The AMP-activated protein kinase (AMPK) is activated by phosphorylation at Thr172, either by the tumor suppressor kinase LKB1 or by an alternate pathway involving the Ca(2+)/calmodulin-dependent kinase, CAMKK2. Increases in AMP:ATP and ADP:ATP ratios, signifying energy deficit, promote allosteric activation and net Thr172 phosphorylation mediated by LKB1, so that the LKB1-AMPK pathway acts as an energy sensor. Many tumor cells carry loss-of-function mutations in the STK11 gene encoding LKB1, but LKB1 re-expression in these cells causes cell cycle arrest. Therefore, it was investigated as to whether arrest by LKB1 is caused by activation of AMPK or of one of the AMPK-related kinases, which are also dependent on LKB1 but are not activated by CAMKK2. In three LKB1-null tumor cell lines, treatment with the Ca(2+) ionophore A23187 caused a G1-arrest that correlated with AMPK activation and Thr172 phosphorylation. In G361 cells, expression of a truncated, CAMKK2 mutant also caused G1-arrest similar to that caused by expression of LKB1, while expression of a dominant negative AMPK mutant, or a double knockout of both AMPK-α subunits, also prevented the cell cycle arrest caused by A23187. These mechanistic findings confirm that AMPK activation triggers cell cycle arrest, and also suggest that the rapid proliferation of LKB1-null tumor cells is due to lack of the restraining influence of AMPK. However, cell cycle arrest can be restored by re-expressing LKB1 or a constitutively active CAMKK2, or by pharmacological agents that increase intracellular Ca(2+) and thus activate endogenous CAMKK2. IMPLICATIONS: Evidence here reveals that the rapid growth and proliferation of cancer cells lacking the tumor suppressor LKB1 is due to reduced activity of AMPK, and suggests a therapeutic approach by which this block might be circumvented

CLASSIFICATION OF STRENGTHENING EXERCISES OF THE LOWER MEMBER POSTERIOR CHAIN, BASED ON THE AMPLITUDE OF MUSCULAR ACTIVATION IN AMATEUR SOCCER PLAYERS BETWEEN 18-25 YEARS

The hamstring injuries are recurrent in the sports disciplines of teams such as football, with rehabilitation being a key point to prevent future alterations. Within this process, the strengthening paradigms are rather empirical, therefore, criteria based on the exercises used are required. In this context, the objective of the present investigation is to classify the strengthening exercises of the posterior lower limb chain, based on the amplitude of muscular activation, in amateur soccer players of the Andres Bello University (UNAB), for which a non-experimental, descriptive, cross-sectional design. The study population was 30 university students, who were studying from first to fifth year, during the academic period 2017. The participants were summoned to the Laboratory of Rehabilitation Sciences, where after signing the informed consent they had to perform a phase of heating on a cycle ergometer, then the MCIV (maximum voluntary isometric contraction) of the semimembranous, semitendinous, biceps femoral and gluteus maximus muscles was calculated, finally applying a battery of strengthening exercises, which were classified according to the intensity of muscle activation. In relation to this, it was obtained that 8 of the 13 exercises implemented were classified as low intensity (p <0.05), 3 of medium intensity (p <0.05) and 2 of high intensity (p <0.05), while the peak of amplitude of the semimembranous, semitendinous and biceps femoral muscles moved to the right in temporal terms, to the extent that the exercises classified as low, medium and high intensity are compared