PGF2alpha-associated vascular smooth muscle hypertrophy is ROS dependent and involves the activation of mTOR, p70S6k, and PTEN.

Prostaglandin F2alpha (PGF2alpha) increases reactive oxygen species (ROS) and induces vascular smooth muscle cell (VSMC) hypertrophy by largely unknown mechanism(s). To investigate the signaling events governing PGF2alpha-induced VSMC hypertrophy we examined the ability of the PGF2alpha analog, fluprostenol to elicit phosphorylation of Akt, the mammalian target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6k), glycogen synthase kinase-3beta (GSK-3beta), phosphatase and tensin homolog (PTEN), extracellular signal-regulated kinase 1/2 (ERK1/2) and Jun N-terminal kinase (JNK) in growth arrested A7r5 VSMC. Fluprostenol-induced hypertrophy was associated with increased ROS, mTOR translocation from the nucleus to the cytoplasm, along with Akt, mTOR, GSK-3beta, PTEN and ERK1/2 but not JNK phosphorylation.

Age-associated changes in MAPK activation in fast- and slow-twitch skeletal muscle of the F344/NNiaHSD X Brown Norway/BiNia rat model.

We compared the tissue content, basal phosphorylation, and stretch-induced phosphorylation of the mitogen-activated protein kinase (MAPK) members; extracellular-signal-regulated kinases (ERK 1/2), p38, and c-Jun NH2-terminal kinase (JNK) in the fast-twitch extensor digitorium longus (EDL) and slow-twitch soleus of young adult (6 month), aged (30 month), and very aged (36 month) F344/NNiaHSD X Brown Norway/BiNia (F344/NXBN) rats. The expression and basal phosphorylation of the ERK 1/2, p38, and JNK MAPK proteins were regulated differently with aging in the EDL and soleus. Stretch induced significant phosphorylation of each signaling molecule in both muscle types of young adult and aged animals.

Regulation of p70S6k, GSK-3beta, and calcineurin in rat striated muscle during aging.

In this study we compared the content and phosphorylation levels of several molecules believed to regulate muscle hypertrophy and fiber type changes in the extensor digitorum longus (EDL), soleus, diaphragm, and heart of adult (6 months), aged (30 months), and very aged (36 months) Fischer 344 x Brown Norway rats. With aging, the mass of the EDL and soleus decreased significantly (approximately 38% and approximately 36%, respectively), the diaphragm's mass remained unchanged while the mass of the heart increased (approximately 35%). Western blotting demonstrated that calcineurin (CnA), the 70-kDa ribosomal S6 kinase (p70(S6k)), glycogen synthase kinase-3beta (GSK-3beta), and the phosphorylated forms of GSK-3beta and p70(S6k) (p-GSK-3beta(Ser9) and p-p70(S6kThr389)) were regulated differently with aging and between muscle types.