Coenzyme Q10 Ameliorates Ultraviolet B Irradiation Induced Cell Death Through Inhibition of Mitochondrial Intrinsic Cell Death Pathway

Ultraviolet B (UVB) induces cell death by increasing free radical production, activating apoptotic cell death pathways and depolarizing mitochondrial membrane potential. Coenzyme Q10 (CoQ10), an essential cofactor in the mitochondrial electron transport chain, serves as a potent antioxidant in the mitochondria. The aim of the present study is to establish whether CoQ10 is capable of protecting neuronal cells against UVB-induced damage. Murine hippocampal HT22 cells were treated with 0.01, 0.1 or 1 μM of CoQ10 3 or 24 h prior to the cells being exposed to UVB irradiation. The CoQ10 concentrations were maintained during irradiation and 24 h post-UVB. Cell viability was assessed by counting viable cells and MTT conversion assay. Superoxide production and mitochondrial membrane potential were measured using fluorescent probes. Levels of cleaved caspase-9, caspase-3, and apoptosis-inducing factor (AIF) were detected using immunocytochemistry and Western blotting. The results showed that UVB irradiation decreased cell viability and such damaging effect was associated with increased superoxide production, mitochondrial depolarization, and activation of caspase-9 and caspase-3. Treatment with CoQ10 at three different concentrations started 24 h before UVB exposure significantly increased the cell viability. The protective effect of CoQ10 was associated with reduction in superoxide production, normalization of mitochondrial membrane potential and inhibition of caspase-9 and caspase-3 activation. It is concluded that the neuroprotective effect of CoQ10 results from inhibiting oxidative stress and blocking caspase-3 dependent cell death pathway

The Effects of a Selective D2 Dopamine Receptor Agonist and Antagonist on D2 Autoreceptor-Mediated Inhibition of Dopamine Release in the Mouse Nucleus Accumbens

This study examined the function of D2 autoreceptors under the influence of a selective dopamine D2 receptor agonist (quinpirole) and antagonist (sulpiride). Inhibition of medial forebrain bundle (MFB) stimulation-evoked dopamine release by activation of D2 autoreceptors was investigated in the nuclues accumbens (NAc) of urethane-anesthetized mice using fixed potential amperometry. Trains of electical stimulation (5-40 pulses at 15 Hz) were applied to the MFB to endogenously activate D2 autoreceptors. Systemic administration of sulpiride blocked D2 autoreceptor-mediated inhibition of dopamine release in the NAc. Intra-NAc microinfusion of quinpirole by itself did not affect D2 autoreceptor-mediated inhibition of dopamine release. However, following pretreatment with sulpiride, intra-NAc microinfusions of quinpirole were effective in augmenting D2 autoreceptor-mediated inhibition of dopamine release. Together, these results suggest that short-term blockade of D2 autoreceptors in the NAc by a selective D2 receptor antagonist enhances the response of these receptors to a selective D2 agonist

Female Magic as a Source of Power in Rosario Ferré’s “Sleeping Beauty”

Capstone Project submitted for English 184.6: Magical Realism (Professor Jenny Sharpe, Winter 2019)

Sequestration of E12/E47 and suppression of p27KIP1 play a role in Id2-induced proliferation and tumorigenesis

Id2 is a member of the helix-loop-helix (HLH) family of transcription regulators known to antagonize basic HLH transcription factors and proteins of the retinoblastoma tumor suppressor family and is implicated in the regulation of proliferation, differentiation, apoptosis and carcinogenesis. To investigate its proposed role in tumorigenesis, Id2 or deletion mutants were re-expressed in Id2−/− dermal fibroblasts. Ectopic expression of Id2 or mutants containing the central HLH domain increased S-phase cells, cell proliferation in low and normal serum and induced tumorigenesis when grafted or subcutaneously injected into athymic mice. Similar to their downregulation in human tumors, the expression of cyclin-dependent kinase inhibitors p27KIP1 and p15INK4b was decreased by Id2; the former by downregulation of its promoter by the Id2 HLH domain-mediated sequestration of E12/E47. Re-expression of p27KIP1 in Id2-overexpressing cells reverted the hyperproliferative and tumorigenic phenotype, implicating Id2 as an oncogene working through p27KIP1. These results tie together the previously observed misregulation of Id2 with a novel mechanism for tumorigenesis

VMY-1-103, a dansylated analog of purvalanol B, induces caspase-3-dependent apoptosis in LNCaP prostate cancer cells

The 2,6,9-trisubstituted purine group of cyclin dependent kinase inhibitors have the potential to be clinically relevant inhibitors of cancer cell proliferation. We have recently designed and synthesized a novel dansylated analog of purvalanol B, termed VMY-1-103, that inhibited cell cycle progression in breast cancer cell lines more effectively than did purvalanol B and allowed for uptake analyses by fluorescence microscopy