The β isoenzyme of Ca2+/calmodulin-dependent kinase type II as possible mediator of somatostatin functions in pituitary tumour cells

Abstract

Abstract. Somatostatin or somatostatin release inhibiting factor (SRIF) analogues are indicated for the treatment of somatotropinomas that hypersecrete growth hormone (GH). Indeed, SRIF inhibits intracellular Ca 2+ concentration ([Ca 2+ ] i ), thus allowing the inhibition of GH secretion. In the present study, our hypothesis was that Ca 2+ /calmodulin-dependent kinase type II (CaMKII), a multifunctional serine/threonine protein kinase, is part of those signalling mechanisms mediating SRIF functions.All four CaMKII isoenzymes (termed α, β, γ and δ) are expressed in rat somatotroph GC cells, although only CaMKIIβ is inhibited by SRIF at both mRNA and protein levels. Similarly to SRIF, the specific knockdown of CaMKIIβ by RNA interference induces a decrease of [Ca 2+ ] i . The effects of SRIF and those of CaMKIIβ knockdown are non-additive. These results are confirmed by the pharmacological blockade of CAMKII. We also observed that, similarly to SRIF, the specific knockdown of CaMKIIβ induces a decrease of both GH content/secretion.These results raise the hypothesis that CaMKIIβ may mediate, at least in part, the SRIF-induced control of [Ca 2+ ] i . In addition, CaMKIIβ seems to play a positive role in maintaining the exocytosis of GH. Our data provide a framework for better elucidating the pathophysiological role of SRIF transduction network in somatotropinomas.

Generation and Behavior Characterization of CaMKIIβ Knockout Mice

“…However, even after the CaMKIIβ KO mice no longer weighed less than the WT littermates, there was still an alteration in body mass composition, with an increased percentage of fat mass that appears highly sensitive to loss of CaMKIIβ. Some evidence indicates that CaMKIIβ may have a function in regulating growth hormone release from the pituitary [25], but more work is necessary to determine the mechanisms behind the changes in body size / composition observed in the CaMKIIβ KO mice.…”

The protein pheromone Er-1 of the ciliate Euplotes raikovi stimulates human T-cell activity: Involvement of interleukin-2 system

“…Western blot experiments for ERK1/2 were performed in agreement with previous reports [22,23,35]. Jurkat cells were seeded in 10 cm 2 Petri dishes at a density of 2.5 Â 10 5 cells/ml, before treatments.…”