Protective effect of Homer 1a against hydrogen peroxide-induced oxidative stress in PC12 cells

Abstract

Oxidative stress-induced cell damage is involved in many neurological diseases. Homer protein, as an important scaffold protein at postsynaptic density, regulates synaptic structure and function. Here, we reported that hydrogen peroxide (H(2)O(2)) induced the expression of Homer 1a. Down-regulation of Homer 1a with a specific small interfering RNA (siRNA) exacerbated H(2)O(2)-induced cell injury. Up-regulation of Homer 1a by lentivirus transfection did not affect the anti-oxidant activity, but significantly reduced the reactive oxygen species (ROS) production and lipid peroxidation after H(2)O(2)-induced oxidative stress. Overexpression of Homer 1a attenuated the loss of mitochondrial membrane potential (MMP) and ATP production induced by H(2)O(2), and subsequently inhibited mitochondrial dysfunction-induced cytochrome c release, increase of Bax/Bcl-2 ratio and caspase-9/caspase-3 activity. Furthermore, in the presence of BAPTA-AM, an intracellular free-calcium (Ca(2+)) chelator, overexpression of Homer 1a had no significant effects on H(2)O(2)-induced oxidative stress. These results suggest that Homer 1a has protective effects against H(2)O(2)-induced oxidative stress by reducing ROS accumulation and activation of mitochondrial apoptotic pathway, and these protective effects are dependent on the regulation of intracellular Ca(2+) homeostasis.

Upregulation of Homer1a Promoted Retinal Ganglion Cell Survival After Retinal Ischemia and Reperfusion via Interacting with Erk Pathway

“…The data are presented as mean ± SEM. Two-way ANOVA followed by a Tukey's test, WT, n = 7; KO, n = 8, *P \ 0.05 (Color figure online) Cell Mol Neurobiol consistent with our previous work on TBI and oxidative injury (Luo et al 2014;Luo et al 2012a). Furthermore, in a retinal I/R injury model, a significant increase in the loss of dendrites and RGCs was found in Homer1a KO mice, compared with those of Homer1a WT mice.…”

“…Inhibition of Erk activation mitigated OGD-induced RGCs apoptosis. Homer1a, as an endogenic neuroprotective protein, was upregulated in neurons by some insults, like glutamate, trauma, and oxidative stress (Luo et al 2012a;Luo et al 2014;Luo et al 2012b). Similar changes of Homer1a and p-Erk were also evident in our previous study in PC12 cells (Luo et al 2012b).…”

“…Our previous studies showed that Homer1a and Homer1b/c play an important role in the development of traumatic brain injury (TBI) via regulation of group I mGluRs (Luo et al 2014;Fei et al 2014). Homer1 proteins were also involved in the regulation of neuronal injury in a model of inflammation (Luo et al 2012b) and oxidative stress (Luo et al 2012a). In this study, we found that downregulation of Homer1a correlated with the loss of RGCs in I/R-injured retinas.…”

“…Our study also suggested that the upregulation of Homer1a disrupted mGluR1-Erk signaling and inhibited the level of p-Erk by inhibiting the release of intracellular Ca 2? in response to neuronal injury (Chen et al 2012;Luo et al 2012a;Luo et al 2014). Thus, the role of Homer 1a and intracellular Ca 2?…”

“…Given the key role of Homer1a in several neurological conditions (Ronesi et al 2012;Luo et al 2014;Luo et al 2012a), it is imperative to investigate its role in promoting RGCs survival. Herein, we found that upregulation of Homer1a in RGCs decreased OGD-induced RGCs apoptosis.…”