Caveolin gene transfer improves glucose metabolism in diabetic mice.

Caveolin, a member of the membrane-anchoring protein family, accumulates various growth receptors in caveolae and inhibits their function. Upregulation of caveolin attenuates cellular proliferation and growth. However, the role of caveolin in regulating insulin signals remains controversial.

Prostaglandin E2-activated Epac promotes neointimal formation of the rat ductus arteriosus by a process distinct from that of cAMP-dependent protein kinase A.

We have demonstrated that chronic stimulation of the prostaglandin E2-cAMP-dependent protein kinase A (PKA) signal pathway plays a critical role in intimal cushion formation in perinatal ductus arteriosus (DA) through promoting synthesis of hyaluronan. We hypothesized that Epac, a newly identified effector of cAMP, may play a role in intimal cushion formation (ICF) in the DA distinct from that of PKA. In the present study, we found that the levels of Epac1 and Epac2 mRNAs were significantly up-regulated in the rat DA during the perinatal period.

Epac1 is upregulated during neointima formation and promotes vascular smooth muscle cell migration.

Vascular remodeling after mechanoinjury largely depends on the migration of smooth muscle cells, an initial key step to wound healing. However, the role of the second messenger system, in particular, the cAMP signal, in regulating such remodeling remains controversial. Exchange protein activated by cAMP (Epac) has been identified as a new target molecule of the cAMP signal, which is independent from PKA.

cAMP-mediated regulation of CYP enzymes and its application in chemotherapy.

Certain anti-cancer prodrugs are subject to cytochrome P450 (CYP)-mediated metabolism and become more active. Because CYP activity may be regulated by phosphorylation via adenylyl cyclase/protein kinase A, selective adenylyl cyclase subtype activators may be utilized in future chemotherapy to regulate CYP activity as a switch in a tumor tissue-specific manner.

Caveolin; different roles for insulin signal?

Caveolae, discovered by electron microscope in the 1950s, are membrane invaginations that accommodate various molecules that are involved in cellular signaling. Caveolin, a major protein component of caveolae identified in 1990s, has been known to inhibit the function of multiple caveolar proteins, such as kinases, which are involved in cell growth and proliferation, and thus considered to be a general growth signal inhibitor. Recent studies using transgenic mouse models have suggested that insulin signal may be exempted from this inhibition, which rather requires the presence of caveolin for proper signaling.

Insulin resistance in skeletal muscles of caveolin-3-null mice.

Type 2 diabetes is preceded by the development of insulin resistance, in which the action of insulin is impaired, largely in skeletal muscles. Caveolin-3 (Cav3) is a muscle-specific subtype of caveolin, an example of a scaffolding protein found within membranes. Cav is also known as growth signal inhibitor, although it was recently demonstrated that the genetic disruption of Cav3 did not augment growth in mice.

Augmentation of immune cell activity against tumor cells by Rauwolfia radix.

In this study, we investigated the effect of Rauwolfia radix on heat shock protein (HSP) 70 expression and cytotoxicity against tumor cells in activated human T cells. When activated T cells were cultured with Rauwolfia radix for 18 h, HSP70 expression after heat shock was remarkably increased, and cytotoxicity against T98G tumor cells was augmented. Moreover, Rauwolfia radix also enhanced the cytotoxicity of heat shocked activated T cells against Molt-4 and T98G tumor cells.