An AD-Related Neuroprotector Rescues Transformed Rat Retinal Ganglion Cells from CoCl2-Induced Apoptosis
ABSTRACT Some ocular diseases characterized by apoptotic death of retinal ganglion cells (RGCs) and Alzheimer's disease (AD) are chronic neurodegenerative disorders and have similarities in neuropathology. Humanin (HN) is known for its ability to suppress neuronal death induced by AD-related insults. In present study, we investigated the neuroprotective effects of HN on hypoxia-induced toxicity in RGC-5 cells. Hypoxia mimetic compound cobalt chloride (CoCl₂) could increase the cell viability loss and apoptosis, whereas HN can significantly attenuate these effects. This finding may provide new therapeutics for the retinal neurodegenerative diseases targeting neuroprotection.
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ABSTRACT: The survival of retinal ganglion cells (RGCs) is a hallmark of many optic neurodegenerative diseases such as glaucoma. YC-1, a potential anticancer drug, is known to be able to decrease the stability and protein expression of hypoxia-inducible factor (HIF)-1α that is triggered by hypoxia and related to RGC survival. We hypothesized that YC-1 may alter RGC cell viability through the down-regulation of HIF-1α. Cell viability of the RGC-5 cell line was measured with a 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Flow cytometry, a LIVE/DEAD viability assay, and high-content screening (HCS) with MKI67 (K(i)-67) monoclonal antibodies were used to detect cell death and cellular proliferation. We found that cells treated with 20 µM YC-1 for 24 h decreased the HIF-1α level in an RGC-5 cell line using immunoblotting and reduced the live cell number in an MTT assay. Results of flow cytometry and HCS demonstrated that reducing the cell proliferation of RGC-5 cells, not cell death, led to the decreased level in the MTT assay. Our findings demonstrate that YC-1-induced down-regulation of HIF-1α might reduce RGC cell proliferation and viability under normoxia, which implies a role of YC-1 in the neuroprotective effect for further clinical applications.Molecular vision 06/2012; 18:1594-603. · 2.25 Impact Factor
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ABSTRACT: Philosophers defined the eye as a window to the soul long before scientists addressed this cliché to determine its scientific basis and clinical relevance. Anatomically and developmentally, the retina is known as an extension of the CNS; it consists of retinal ganglion cells, the axons of which form the optic nerve, whose fibres are, in effect, CNS axons. The eye has unique physical structures and a local array of surface molecules and cytokines, and is host to specialized immune responses similar to those in the brain and spinal cord. Several well-defined neurodegenerative conditions that affect the brain and spinal cord have manifestations in the eye, and ocular symptoms often precede conventional diagnosis of such CNS disorders. Furthermore, various eye-specific pathologies share characteristics of other CNS pathologies. In this Review, we summarize data that support examination of the eye as a noninvasive approach to the diagnosis of select CNS diseases, and the use of the eye as a valuable model to study the CNS. Translation of eye research to CNS disease, and deciphering the role of immune cells in these two systems, could improve our understanding and, potentially, the treatment of neurodegenerative disorders.Nature Reviews Neurology 11/2012; 9(1). DOI:10.1038/nrneurol.2012.227 · 14.10 Impact Factor
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ABSTRACT: The discovery of humanin, a novel, mitochondria-derived peptide, has created a potentially new category of biologically active peptide. As more research unravels the endogenous role of humanin as well as its potential pharmacological use, its role in stress resistance has become clearer. Humanin protects cells from oxidative stress, serum starvation, hypoxia, and other insults in vitro and also improves cardiovascular disease as well as Alzheimer's disease in vivo. In this review we discuss the emerging role of humanin in stress resistance and its proposed mechanism of action.Journal of Molecular Endocrinology 12/2012; 50(1). DOI:10.1530/JME-12-0203 · 3.62 Impact Factor