In: General Physiology and Biophysics, vol. 30, no. 3
Rok, strany: 2011, 251 - 262
Somatostatin or somatostatin release inhibiting factor (SRIF) analogues are indicated for the treatment of somatotropinomas that hypersecrete growth hormone (GH). Indeed, SRIF inhibits intracellular Ca2+ concentration ([Ca2+]
i), thus allowing the inhibition of GH secretion. In the present study, our hypothesis was that Ca2+/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 [Ca2+] 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 [Ca2+] 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.
Cervia, D. 2011. The β isoenzyme of Ca2+/calmodulin-dependent kinase type II as possible mediator of somatostatin functions in pituitary tumour cells. In General Physiology and Biophysics, vol. 30, no.3, pp. 251-262. 0231-5882.
Cervia, D. (2011). The β isoenzyme of Ca2+/calmodulin-dependent kinase type II as possible mediator of somatostatin functions in pituitary tumour cells. General Physiology and Biophysics, 30(3), 251-262. 0231-5882.