Munki Kim

Anticancer Effect of Nemopilema nomurai Jellyfish Venom on HepG2 Cells and a Tumor Xenograft Animal Model

Various kinds of animal venoms and their components have been widely studied for potential therapeutic applications. This study evaluated whether Nemopilema nomurai jellyfish venom (NnV) has anticancer activity. NnV strongly induced cytotoxicity of HepG2 cells through apoptotic cell death, as demonstrated by alterations of chromatic morphology, activation of procaspase-3, and an increase in the Bax/Bcl-2 ratio. Furthermore, NnV inhibited the phosphorylation of PI3K, PDK1, Akt, mTOR, p70S6K, and 4EBP1, whereas it enhanced the expression of p-PTEN. Interestingly, NnV also inactivated the negative feedback loops associated with Akt activation, as demonstrated by downregulation of Akt at Ser473 and mTOR at Ser2481. The anticancer effect of NnV was significant in a HepG2 xenograft mouse model, with no obvious toxicity. HepG2 cell death by NnV was inhibited by tetracycline, metalloprotease inhibitor, suggesting that metalloprotease component in NnV is closely related to the anticancer effects. This study demonstrates, for the first time, that NnV exerts highly selective cytotoxicity in HepG2 cells via dual inhibition of the Akt and mTOR signaling pathways, but not in normal cells.

Dopamine D3 receptor-modulated neuroprotective effects of lisuride

&NA; Dopamine (DA) contributes to the regulation of voluntary movement, and a deficiency in DAergic neurons leads to movement disorders. The objective of this study was to examine the neuroprotective effect of DA D2‐like receptor agonist, lisuride, and the role of DA receptors in this protection. Treatment with lisuride alleviated loss of tyrosine hydroxylase (TH) both direct and intraperitoneal injection in 6‐hydroxydopamine (6‐OHDA) mouse model. Similar results were obtained in primary neuronal cultures treated with lisuride. Lisuride protected TH expression against 6‐OHDA‐induced cytotoxicity in a concentration‐dependent manner. Then, we evaluated the role of DA D2 and D3 receptor in neuroprotective effect of lisuride. Treatment of neuronal cultures with L‐741,626, a DA D2 receptor‐selective antagonist, did not alter neuroprotective effect of lisuride. However, protective effect of lisuride on TH expression was abolished when cells were treated with GR103691, a D3 receptor selective antagonist. Furthermore, whether lisuride can alleviate mitochondrial damage of DAergic neurons induced by 6‐OHDA, we investigated the expression of the mitochondrial regulatory protein, paraplegin, and changes in mitochondria morphology. Treatment with lisuride countered a 6‐OHDA‐induced reduction in paraplegin and TH expression, and co‐treatment with GR103691 blocked this effect of lisuride. Transmission electron microscopy confirmed the lisuride mitigation of 6‐OHDA‐induced damage to the mitochondrial membrane and cristae. These results suggest that the DA D3 receptor mediates the neuroprotective effects of lisuride by preventing mitochondrial damage. HighlightsThe dopamine D2‐like receptor agonist lisuride has neuroprotective effects.Lisuride injected into the mouse substantia nigra countered 6‐OHDA neurotoxicity.Lisuride prevented 6‐OHDA‐induced damage in neuronal mitochondria.Lisurides neuroprotective actions were blocked by a D3 receptor antagonist.The D3 receptor mediates lisuride‐induced neuroprotection in dopaminergic neurons.

Scanning Electron Microscopic Study of the Developing Vallate Papillaein the Korean Native Goat (Capra hircus)

ABSTRACT The purpose of the present study was to investigate the morphological characteristics of the developing vallate papillae (VP) of Korean native goats using scanning electron microscopy. In prenatal development of the VP, primordia of the VP were observed and the moat was shallowly spread in 60-day-old fetuses. The moat of the vallate papillae was shallowly spread and still undifferentiated in 90-day-old fetuses. The trench wall of the moat of the VP was well developed in 120-day-old fetuses. In neonates, the moat of the VP was more widely and deeply engraved and VP were developed as completely as those of adults. In postnatal development, VP were observed to have continually increased in size with slight morphological changes until 90-days after birth. Taste pores of the VP were shaped like flower leaves in 120-days after birth. The microridges and microplicaes were well developed on the epithelial surface of the VP in goats ranging from 120-day-old fetuses to 120-day-old postnatal animals. These results suppose that the sensing ability for gestation of VP was already well developed by the time of its birth and VP were differentiated into a variety of different shape and size during development.