The (Na(+)/K (+))-ATPase activity in the developing rat retina: the role of insulin-like growth factor-I (IGF-I)

• Published in: Cellular and molecular neurobiology Vol. 35; no. 2; p. 243
• Main Authors: Maturana-Teixeira, Sheila, Braga, Luis Eduardo Gomes, Carpi Santos, Raul, Calaza, Karin da Costa, Giestal-de-Araujo, Elizabeth, Leão-Ferreira, Luiz Roberto
• Format: Journal Article
• Language: English
• Published: Netherlands 01.03.2015
• Subjects: Animals; Animals, Newborn; Catalytic Domain; Insulin-Like Growth Factor I - metabolism; Isoenzymes - metabolism; Phosphatidylinositol 3-Kinases; Phosphorylation; Proto-Oncogene Proteins c-akt - metabolism; Rats; Retina - enzymology; Retina - growth & development; Signal Transduction; Sodium-Potassium-Exchanging ATPase - metabolism
• ISSN: 1573-6830; 1573-6830
• DOI: 10.1007/s10571-014-0119-9

In this work, the (Na(+)/K(+))-ATPase activity was evaluated during the early stages of the postnatal development of rat retina and showed an almost three-time increase from P0 to P14. Expression of the three catalytic subunit isoforms (α1, α2, and α3) of the (Na(+)/K(+))-ATPase was also evaluated by immunoblot in the same period, but no correlation to the catalytic activity increment was observed. On the other hand, immunolocalization of these three α-catalytic isoforms in the developing retina showed an age-related pattern. Involvement of IGF-I in the stimulation of the (Na(+)/K(+))-ATPase was investigated. Our results demonstrate that the exogenous IGF-I (10 ng/mL) stimulates enzyme activity at the age of P7 only. Incubation of retinas with 10 μM I-OMe-AG 538 (inhibitor of the IGF-I receptor) indicates that the basal (Na(+)/K(+))-ATPase activity is sustained by endogenous IGF-I in P7 animals. These data were corroborated by an age-dependent decrease in the immunodetection of endogenous IGF-I as well as in the phosphorylation level of its cognate receptor in rat retina homogenates. The signaling pathway involved in IGF-I-induced modulation of the (Na(+)/K(+))-ATPase was also investigated. Our data show that the inhibitory effects induced by I-OMe-AG 538 and the PI 3-kinase inhibitor Ly 294002 on the basal (Na(+)/K(+))-ATPase activity were non-cumulative. Furthermore, IGF-I induced phosphorylation of PKB in a Ly 294002-sensitive manner. Together, these data demonstrate that the PI 3-kinase/PKB signaling pathway is involved in the IGF-I-sustained basal (Na(+)/K(+))-ATPase activity during the first 7 days of the postnatal development of rat retina.