• BMB Reports
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• 제45권1호
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• pp.7-13
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• 2012

Phospholipase D (PLD), a superfamily of signaling enzymes that most commonly generate the lipid second messenger Phosphatidic Acid (PA), is found in diverse organisms from bacteria to man and functions in multiple cellular pathways. A fascinating member of the family, MitoPLD, is anchored to the mitochondrial surface and has two reported roles. In the first role, MitoPLD-generated PA regulates mitochondrial shape through facilitating mitochondrial fusion. In the second role, MitoPLD performs a critical function in a pathway that creates a specialized form of RNAi required by developing spermatocytes to suppress transposon mobilization during meiosis. This spermatocyte-specific RNAi, known as piRNA, is generated in the nuage, an electron-dense accumulation of RNA templates and processing proteins that localize adjacent to mitochondria in a structure also called intermitochondrial cement. In this review, we summarize recent findings on these roles for MitoPLD functions, highlighting directions that need to be pursued to define the underlying mechanisms.

• 운동영양학회지
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• 제16권1호
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• pp.1-9
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• 2012

Long chain fatty acids (LCFAs) are transported into cells via plasma transporters, are activated to fatty acyl-CoA by fatty acyl-CoA synthase (ACS), and enter mitochondria via the carnitine system (CPT1/CACT/CPT2). The mitochondrial carnitine system plays an obligatory role in β-oxidation of LCFAs by catalyzing their transport into the mitochondrial matrix. Fatty acyl-CoAs are oxidized via the β-oxidation pathway, which results in the production of acetyl-CoA. The acetyl-CoA can be imported into the tricarboxylic acid (TCA) cycle for oxidation in the mitochondrial matrix or can be used for malonyl-CoA synthesis by acetyl-CoA carboxylase 2 (ACC2) in the cytoplasm. In skeletal muscle, ACC2 catalyzes the carboxylation of acetyl-CoA to form malonyl-CoA, which is a potent endogenous inhibitor of carnitine palmitoyltransferase 1 (CPT1). Thus, ACC2 indirectly inhibits the influx of fatty acids into the mitochondria. Fatty acid metabolism can also be regulated by malonyl-CoA-mediated inhibition of CPT1.

• 대한의생명과학회지
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• 제17권3호
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• pp.177-184
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• 2011

Potassium cyanate (KOCN) is an inorganic compound and induces the carbamylation of proteins with cytotoxic effects on human cells. Although there is a potential cytotoxic molecule, the role of KOCN on the apoptosis of cancer cell is not well understood. The present study investigated the effects of KOCN on the human colorectal cancer cell line, HCT 116 cells. To understand the anti-cancer effect of KOCN on HCT 116 cells, we examined alteration of apoptosis, the intracellular $Ca^{2+}$ concentration, the intracellular signaling pathway and generation of reactive oxygen species (ROS) in these cells treated with KOCN. The apoptosis of HCT 116 cells was induced by KOCN in a dose-dependent manner at 24 hours and 48 hours, respectively. The apoptosis was processed via the cleavage of poly ADP-ribose polymerase (PARP) and activation of caspase 3 in HCT 116 cells. KOCN induced the elevation of intracellular $Ca^{2+}$ concentration and changed the expressions of Bcl-2 family proteins. The pro-apoptotic Bax was continuously up-regulated, and the anti-apoptotic Bcl-2 was down-regulated by KOCN. KOCN also induced the hyperpolarization of mitochondria and the generation of ROS in HCT 116 cells. Taken together, these results indicate that KOCN induces the apoptosis of HCT 116 cells by disruption of $Ca^{2+}$ homeostasis and via mitochondrial pathway. This study provides the compound that may be used as a potent agent for the treatment of colorectal cancer.

• The Korean Journal of Physiology and Pharmacology
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• 제9권4호
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• pp.239-246
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• 2005

In the central nervous system, nitric oxide (NO) is associated with many pathological diseases such as brain ischemia, neurodegeneration and inflammation. The epigallocatechin gallate (EGCG), a major compound of green tea, is recognized as protective substance against neuronal diseases. This study is aimed to investigate the effect of EGCG on NO-induced cell death in PC12 cells. Administration of sodium nitroprusside (SNP), a NO donor, decreased cell viability in a dose- and time-dependent manner and induced genomic DNA fragmentation with cell shrinkage and chromatin condensation. EGCG diminished the decrement of cell viability and the formation of apoptotic morphologenic changes as well as DNA fragmentation by SNP. EGCG played as an antioxidant that attenuated the production of reactive oxygen species (ROS) by SNP. The cells treated with SNP showed downregulation of Bcl-2, but upregulation of Bax. EGCG ameliorated the altered expression of Bcl-2 and Bax by SNP. The release of cytochrome c from mitochondria into cytosol and expression of voltage -dependent anion channel (VDAC)1, a cytochrome c releasing channel in mitochondria, were increased in SNP-treated cells, whereas were attenuated by EGCG. The enhancement of caspase-9, preceding mitochondria-dependent pathway, caspase-8 and death receptor-dependent pathway, as well as caspase-3 activities were suppressed by EGCG. SNP upragulated Fas and Fas-L, which are death receptor assembly, whereas EGCG ameliorated the expression of Fas enhanced by SNP. These results demonstrated that EGCG has a protective effect against SNP-induced apoptosis in PC12 cells, through scavenging ROS and regulating the mitocondria- and death receptor-mediated signal pathway. The present study suggest that EGCG might be a natural neuroprotective substance.

• Molecules and Cells
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• 제37권9호
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• pp.672-684
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• 2014

The exact causes of cell death in Parkinson's disease (PD) remain unknown despite extensive studies on PD.The identification of signaling and metabolic pathways involved in PD might provide insight into the molecular mechanisms underlying PD. The neurotoxin 1-methyl-4-phenylpyridinium ($MPP^+$) induces cellular changes characteristic of PD, and $MPP^+$-based models have been extensively used for PD studies. In this study, pathways that were significantly perturbed in $MPP^+$-treated human neuroblastoma SH-EP cells were identified from genome-wide gene expression data for five time points (1.5, 3, 9, 12, and 24 h) after treatment. The mitogen-activated protein kinase (MAPK) signaling pathway and endoplasmic reticulum (ER) protein processing pathway showed significant perturbation at all time points. Perturbation of each of these pathways resulted in the common outcome of upregulation of DNA-damage-inducible transcript 3 (DDIT3). Genes involved in ER protein processing pathway included ubiquitin ligase complex genes and ER-associated degradation (ERAD)-related genes. Additionally, overexpression of DDIT3 might induce oxidative stress via glutathione depletion as a result of overexpression of CHAC1. This study suggests that upregulation of DDIT3 caused by perturbation of the MAPK signaling pathway and ER protein processing pathway might play a key role in $MPP^+$-induced neuronal cell death. Moreover, the toxicity signal of $MPP^+$ resulting from mitochondrial dysfunction through inhibition of complex I of the electron transport chain might feed back to the mitochondria via ER stress. This positive feedback could contribute to amplification of the death signal induced by $MPP^+$.

• 대한한방부인과학회지
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• 제18권1호
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• pp.29-44
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• 2005

To address the ability of Herba Portulacae(HP) to induce cell death, we investigated the effect of HP on cell viability. Twenty-four hours later, loss of viability occurred following HP exposure in a dose-dependent manner. The treatment of HP, a commonly used herb formulation in Korea, Japan and China, caused a decrease in cell viability. HP also resulted in apoptotic morphology a brightly blue-fluorescent condensed nuclei by Hoechst 33258-staining, and reduction of cell volume. Our results show that 2mg/ml HP induces mitochondria membrane potential collapse. Immunoblotting data also shows that the expression of Bcl-2, antiaoptotic protein, decrease by the addition of HP. This GFP-Bax overexpression system shows that an important pro-apoptotic Bcl-2-family protein, Bax is translocated to mitochondria by the addition of 2mg/ml HP. Inerestingly, MAPK inhibitor study shows that p38 MAPK inhibitor, SB203580 inhibits HP-induced cell death and caspase-3 activation in HP-treated HeLa cells. Furthermore, HP transiently but significantly induces p38 activation. But P38 MAPK inhibitor does not have any effect on the translocation of Bax. Considering these results, HP induces apoptosis via p38 MAPK activation. But the pathway does not involve the translocation of Bax.

• 한국환경성돌연변이발암원학회:학술대회논문집
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• 한국환경성돌연변이발암원학회 2003년도 추계학술대회
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• pp.146-146
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• 2003

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2008년도 제49회 학술심포지움 및 국제학술대회
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• pp.88.1-88.1
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• 2008

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2008년도 제49회 학술심포지움 및 국제학술대회
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• pp.88.2-88.2
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• 2008

• 한국생명과학회:학술대회논문집
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• 한국생명과학회 2007년도 제48회 학술심포지움 및 추계국제학술대회
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• pp.42.2-42.2
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• 2007

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