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Joungjoa Park

Publications and source records attributed to Joungjoa Park.

6 recordsLinked to original sources
PubMed2006

A peptide against the N-terminus of myristoylated alanine-rich C kinase substrate inhibits degranulation of human leukocytes in vitro.

Leukocytes synthesize a variety of inflammatory mediators that are packaged and stored in the cytoplasm within membrane-bound granules. Upon stimulation, the cells secrete the granule contents via an exocytotic process whereby the granules translocate to the cell periphery, the granule membranes fuse with the plasma membrane, and the granule contents are released extracellularly. We have reported previously that another exocytotic process, release of mucin by secretory cells of the airway epithelium, is regulated by the myristoylated alanine-rich C kinase substrate (MARCKS) (Li Y, Martin LD, Spizz G, Adler KB. MARCKS protein is a key molecule regulating mucin secretion by human airway epithelial cells in vitro. J Biol Chem 2001;276:40982-40990; Singer M, Martin LD, Vargaftig BB, Park J, Gruber AD, Li Y, Adler KB. A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma. Nat Med 2004;10:193-196). In those studies, mucin secretion in vitro and in vivo was attenuated by a synthetic peptide identical to the N-terminus of MARCKS, named the MANS peptide (Li and colleagues, 2001). In this study, we used the MANS peptide to investigate possible involvement of MARCKS in secretion of leukocyte granule proteins. In neutrophils isolated from human blood, phorbol 12-myristate 13-acetate-induced myeloperoxidase release was attenuated in a concentration-dependent manner by MANS but not by equal concentrations of a missense control peptide. In additional studies using human leukocyte cell lines, secretion of eosinophil peroxidase from the eosinophil-like cell line HL-60 clone 15, lysozyme from the monocytic leukemia cell line U937, and granzyme from the lymphocyte natural killer cell line NK-92 were attenuated by preincubation of the cells with MANS but not with the missense control peptide. The results indicate that MARCKS protein may play an important role in the secretion of membrane-bound granules from different leukocytes. MARCKS may be an important component of secretory pathways associated with release of granules by different cell types.

Cell Degranulation↗
PubMed2004

A MARCKS-related peptide blocks mucus hypersecretion in a mouse model of asthma.

Mucus hypersecretion is a crucial feature of pulmonary diseases such as asthma, chronic bronchitis and cystic fibrosis. Despite much research, there is still no effective therapy for this condition. Recently, we showed that the myristoylated, alanine-rich C-kinase substrate (MARCKS) protein is required for mucus secretion by human bronchial epithelial cells in culture. Having synthesized a peptide corresponding to the N-terminal domain of MARCKS, we now show that the intratracheal instillation of this peptide blocks mucus hypersecretion in a mouse model of asthma. A missense peptide with the same amino acid composition has no effect. Based on quantitative histochemical analysis of the mouse airways, the peptide seems to act by blocking mucus release from goblet cells, possibly by inhibiting the attachment of MARCKS to membranes of intracellular mucin granules. These results support a pivotal role for MARCKS protein, specifically its N-terminal region, in modulating this secretory process in mammalian airways. Intratracheal administration of this MARCKS-related peptide could therapeutically reduce mucus secretion in the airways of human patients with asthma, chronic bronchitis and cystic fibrosis.

Animals↗
PubMed2002

Effects of 2-butoxyethanol on hepatic oxidative damage.

2-Butoxyethanol has been reported to induce an increase in liver tumors in male B6C3F1 mice following chronic inhalation while rats, similarly treated, showed no increase in liver tumors. The mechanism for the selective induction of cancer in mouse liver is unknown, however, 2-butoxyethanol has been shown to induce hemolysis in mice, resulting in an accumulation of hemosiderin (iron) in the liver. Previous studies by our group and others have shown that mouse liver compared to other rodent species has a lower antioxidant capacity and appears to be more susceptible to chemically-induced oxidative damage. Since iron is known to produce hydroxyl radicals (through the Fenton reaction), we have proposed that the 2-butoxyethanol-induced iron overload (through hemolysis) may contribute to the induction of liver neoplasia in the mouse. In the present studies, 2-butoxyethanol induced oxidative stress in the liver of mice following 7-day treatment by gavage. These studies also examined whether 2-butoxyethanol, 2-butoxy acetic acid (a major metabolite of 2-butoxyethanol) or iron (FeSO(4)) produced oxidative stress in mouse and rat hepatocytes. Oxidative stress was examined by measuring oxidative DNA damage (OH8dG), lipid peroxidation (MDA formation) and cellular vitamin E concentrations. Neither 2-butoxyethanol or 2-butoxyacetic acid induced changes in the oxidative stress parameters examined in either rat or mouse hepatocytes. In contrast, FeSO(4) produced a dose-related increase in OH8dG and MDA and a decrease in vitamin E levels following 24 h treatment. Mouse hepatocytes were more sensitive than rat hepatocytes to the oxidative damage induced by the FeSO(4). FeSO(4)-induced oxidative stress was not increased by co-treatment of FeSO(4) with either 2-butoxyethanol or 2-butoxy acetic acid. These results support the proposal that the induction of hepatic oxidative stress by 2-butoxyethanol in vivo occurs secondary to induction of hemolysis and iron deposition in the liver rather than as a direct action of 2-butoxyethanol or its main metabolite, 2-butoxy acetic acid.

8-Hydroxy-2'-Deoxyguanosine↗
PubMed2002

Acrylamide-induced cellular transformation.

Acrylamide is a monomer of polyacrylamide, whose products are used in biochemistry, the manufacture of paper, water treatment, and as a soil stabilizer. While polymeric acrylamide is nontoxic, the monomer can cause several toxic effects and has the potential for human occupational exposure. While acrylamide is not mutagenic in prokaryotic mutagenesis assays, chronic acrylamide treatment in rodents has been shown to produce tumors in both rats and mice. The mechanism for the induction of tumors by acrylamide is not known. In the present study, we examined the possibility that acrylamide might induce cellular transformation, using Syrian hamster embryo (SHE) cell morphological transformation as well as potential mechanisms for the cellular transformation. Results showed that treatment with 0.5 mM and higher concentrations of acrylamide continuously for 7 days induced morphological transformation. Cotreatment with acrylamide and N-acetyl-L-cysteine (NAC), a sulfhydryl group donor, resulted in the reduction of acrylamide-induced morphological transformation in SHE cells. Cotreatment with 1-aminobenzotriazole (ABT), a nonspecific P450 inhibitor, and acrylamide produced no change in morphological transformation when compared to acrylamide treatment only. Cotreatment with acrylamide and DL-buthionone-[S,R]-sulfoximine (BSO), a selective inhibitor of gamma-glutamylcysteine synthetase, increased the percent of morphologically transformed colonies compared to acrylamide treatment alone. Acrylamide reduced GSH levels in SHE cells, and cotreatment with acrylamide and NAC prevented the acrylamide-induced reduction of GSH. BSO treatment with acrylamide enhanced the depletion of GSH. These results suggest that acrylamide itself, but not oxidative P450 metabolites of acrylamide appear to be involved in acrylamide-induced cellular transformation and that cellular thiol status (possibly GSH) is involved in acrylamide-induced morphological transformation.

Acetylcysteine↗
PubMed2002

Mechanisms of 2-butoxyethanol carcinogenicity: studies on Syrian Hamster Embryo (SHE) cell transformation.

Previous studies showed that 2-butoxyethanol increased liver tumors in B6C3F1 mice following chronic exposure. While the mechanism of 2-butoxyethanol-induced liver carcinogenicity has not been defined, 2-butoxyethanol has been shown to induce hemolysis in rodents via 2-butoxyacetic acid, the major metabolite of 2-butoxyethanol. This toxic effect, coupled with the observation that continued treatment with 2-butoxyethanol results in hemosiderin deposition in the liver, has led to our hypothesis that liver carcinogenicity by 2-butoxyethnaol is mediated via oxidative stress (iron catalyzed) and Kupffer cell activation. The present study used Syrian Hamster Embryo (SHE) cell transformation, a surrogate in vitro model for carcinogenesis in vivo, to examine whether 2-butoxyethanol, 2-butoxyacetic acid, or iron (ferrous sulfate) produced cell transformation. SHE cells were treated with either 2-butoxyethanol (0.5-20 mM), 2-butoxyacetic acid (0.5-20 mM), or ferrous sulfate (0.5-75 microg/ml) for 7 days. 2-Butoxyethanol and 2-butoxyacetic acid did not induce cellular transformation. In contrast, treatment with ferrous sulfate (2.5 and 5.0 microg/ml) increased morphological transformation. Cotreatment of ferrous sulfate with the antioxidants alpha-tocopherol (vitamin E) or (-)-epigallocatechin-3-gallate (EGCG) prevented ferrous sulfate-induced transformation, suggesting the involvement of oxidative stress in SHE cell transformation. The level of oxidative DNA damage (OH8dG) increased following ferrous sulfate treatment in SHE cells; additionally, using single cell gel electrophoresis (comet assay), ferrous sulfate treatment produced an increase in DNA damage. Both DNA lesions were decreased by cotreatment of ferrous sulfate with antioxidants. These data support our proposal that iron, produced indirectly through hemolysis, and not 2-butoxyethanol or its metabolite 2-butoxyacetic acid, is responsible for the observed carcinogenicity of 2-butoxyethanol.

Animals↗