[Show abstract][Hide abstract] ABSTRACT: The Akt signaling pathway plays a key role in promoting the survival of various types of cells from stress-induced apoptosis, and different members of the Akt family display distinct physiological roles. Previous studies have shown that in response to UV irradiation, Akt2 is sensitized to counteract the induced apoptosis. However, in response to oxidative stress such as hydrogen peroxide, it remains to be elucidated what member of the Akt family would be activated to initiate the signaling cascades leading to resistance of the induced apoptosis. In the present study, we present the first evidence that knockdown of Akt1 enhances cell survival under exposure to 50 μM H(2)O(2). This survival is derived from selective upregulation and activation of Akt2 but not Akt3, which initiates 3 major signaling cascades. First, murine double minute 2 (MDM2) is hyperphosphorylated, which promotes p53 degradation and attenuates its Ser-15 phosphorylation, significantly attenuating Bcl-2 homologous antagonist killer (Bak) upregulation. Second, Akt2 activation inactivates glycogen synthase kinase 3 beta (GSK-3β) to promote stability of myeloid leukemia cell differentiation protein 1 (MCL-1). Finally, Akt2 activation promotes phosphorylation of FOXO3A toward cytosolic export and thus downregulates Bim expression. Overexpression of Bim enhances H(2)O(2)-induced apoptosis. Together, our results demonstrate that among the Akt family members, Akt2 is an essential kinase in counteracting oxidative-stress-induced apoptosis through multiple signaling pathways.
[Show abstract][Hide abstract] ABSTRACT: The c-Jun N-terminal kinases (JNKs) are members of the mitogen-activated protein kinase family. Their functions in regulating animal development have been well studied in both invertebrates and vertebrates. However, it remains to be determined whether they play a role in sex determination. Here we present first evidence to show that expression of JNK1 displays distinct patterns during sex reversal of rice-field eel. Molecular cloning reveals that JNK1 is well conserved among rice-field eel and other vertebrates. Both quantitative real-time polymerase chain reaction and Western blot analysis demonstrate that JNK1 is highly expressed in the ovary of the female individual and reduced to a substantial degree at the later stage of the intersex. However, when the intersex individual develops into the stage of male, expression of the JNK1 in the testis of the male individual is distinctly downregulated. Associated with the contrast JNK1 expression pattern in female and male gonads, several stem cell marker genes including Nanog, Oct-3/4, and Sox-2 were also differentially expressed in female and male germinal stem cells. Together, these results suggest it is possible that JNK1 plays an important role in sexual reversal of the rice-field eel.
No preview · Article · Jan 2009 · Journal of Experimental Zoology Part B Molecular and Developmental Evolution