Expression of the estrogen‐regulated gene Nip2 during rat brain maturation

Abstract

The present study stems from previous observations demonstrating that in the neuroblastoma cell line SK-ER3 the mRNA content of the pro-apoptotic gene Nip2 is decreased following treatment with estradiol. We investigate the content of Nip2 mRNA during the maturation of rat embryo brain and we show that Nip2 mRNA is very low at embryo day 15 and steadily increases up to day 20. At day 21 Nip2 mRNA is decreased almost to the low levels observed in the mature brain. Studies in neurons from rat embryo at day 18 show that Nip2 mRNA content is significantly decreased by exposure to estradiol at 1 nM concentration demonstrating that the observations previously done in the SK-ER3 neuroblastoma cell line can be reproduced in neurons in culture. The finding that estrogens may modulate the activity of Nip2 gene activity may be of relevance not only with regard to the effects of estradiol on brain maturation, but also for the understanding of the neuroprotective effects recently described for this hormone.

Estrogen Activates Classical and Alternative Mechanisms to Orchestrate Neuroprotection

“…To date, a number of studies have unambiguously shown that 17β-estradiol can modulate the expression of antiapoptotic proteins Bcl-2 and/or Bcl-Xl in hippocampal and cortical neurons (Dubal et al, 1999;Pike, 1999;Nilsen and Diaz Brinton, 2003). In addition, estradiol can induce down-regulation of proapoptotic Bad or Nip-2, which is a negative regulator or Bcl-2 (Gollapudi and Oblinger, 1999b;Brusadelli et al, 2000). Many of these proteins are involved in neurotoxic effects elicited by oxidative stress, Aβ, excitotoxic insults, or following brain ischemia, which are often associated with a reduction of Bcl-2 and/or up regulation of Bad/Bax.…”

“…Rat pheochromocytoma PC12 cells and neurons from rat embryo Serum and NGF withdrawal induced apoptosis Gollapudi and Oblinger, 1999b;Brusadelli et al, 2000 Cerebral cortex Ischemia and stroke like injury Dubal et al, 1999;Rau et al, 2003 Onoue et al, 2002 and the impaired cognitive functions once they have been established (Baldereschi et al ., 1998;Pike, 1999;Waring et al, 1999).…”

BNIP-2 induces cell elongation and membrane protrusions by interacting with Cdc42 via a unique Cdc42-binding motif within its BNIP-2 and Cdc42GAP homology domain

“…Currently, the physiological role(s) of BNIP-2 and its effect on GTPase signaling in vivo have not been elucidated. In another study, the expression of BNIP-2 was shown to be down-regulated upon 17 beta-estradiol treatment in SK-ER3 neuroblastoma cells [20], indicating a possible role in the estrogenic effect on cell survival, whereas the expression of its mouse homolog mBNIP21 in the heart was also downregulated upon coxsackievirus B3 infection in an CVB3-myocarditis model [21], indicating a potential role in the pathogenesis of viral myocarditis. Recently, we have characterized a novel member of the BNIP-2 family, termed BNIP-Sa, whose expression induced profound effects in cellular morphology.…”