Biomedical subjects

Soo Jung Kim

Publications and source records attributed to Soo Jung Kim.

11 recordsLinked to original sources

PubMed2006

Substrate-specific translocational attenuation during ER stress defines a pre-emptive quality control pathway.

Eukaryotic proteins entering the secretory pathway are translocated into the ER by signal sequences that vary widely in primary structure. We now provide a functional rationale for this long-observed sequence diversity by demonstrating that differences among signals facilitate substrate-selective modulation of protein translocation. We find that during acute ER stress, translocation of secretory and membrane proteins is rapidly and transiently attenuated in a signal sequence-selective manner. Their cotranslational rerouting to the cytosol for degradation reduces the burden of misfolded substrates entering the ER and represents a pathway for pre-emptive quality control (pQC). Bypassing the pQC pathway for the prion protein increases its rate of aggregation in the ER lumen during prolonged stress and renders cells less capable of viable recovery. Conversely, pharmacologically augmenting pQC during ER stress proved protective. Thus, protein translocation is a physiologically regulated process that is utilized for pQC as part of the ER stress response.

Animals↗

PubMed2006

Role of E2F1 in endoplasmic reticulum stress signaling.

The transcription factor E2F1 coordinates cell cycle progression and induces apoptosis in response to DNA damage stress. Aside from DNA damage, the role of E2F1 in the endoplasmic reticulum (ER) stress signaling pathways is unclear. We found that E2F1-/- murine embryonic fibroblasts (MEFs) are resistant to apoptosis triggered by the ER stress inducer thapsigargin. In addition, E2F1 deficiency results in enhanced phosphorylation of eukaryotic translation initiation factor 2a (eIF2a). These results therefore indicate that E2F1 deficiency increases phosphorylation of eIF2a in response to ER stress triggered by thapsigargin, and suggest that the reduction in ER stress-induced apoptosis in E2F1-deficient cells is related to the high level of eIF2a phosphorylation.

Animals↗

PubMed2006

Hepatocellular carcinoma model cell lines with two distinct migration modes.

Migration is an essential feature of metastatic cancer cells. To understand how motility is regulated in hepatocellular carcinoma, we analyzed gene expression profiles of mouse model cell lines we established from transgenic mice carrying SV40 large T antigen. A non-motile HC9 cell line was isolated from mouse liver tumors, and two additional cell lines, HCM1 and HCM4, were derived from HC9 cells. We found that both HCM1 and HCM4 cells were substantially more migratory than HC9, and that HCM1 generated tumor nodules in nude mice. In contrast to HCM4 cells that exhibited mesenchymal cell-type gene expression similar to HC9 cells, HCM1 cells appeared to have undergone a mesenchymal-amoeboidal transition. Thus, HCM1 and HCM4 cells have distinct migration and gene expression patterns, and together with HC9 cells, they can serve as model cell lines for understanding how migration is acquired and controlled in hepatocellular carcinoma.

Animals↗

PubMed2006

Severe hypothyroidism induced by thyroid metastasis of colon adenocarcinoma: a case report and review of the literature.

An 85-year-old man who had undergone a right hemicolectomy for colon cancer presented with severe hypothyroidism and hoarseness 21 months after the operation. The serum thyrotropin (TSH) was markedly elevated to 118.14 microIU/mL and serum free thyroxine (fT4) level was markedly suppressed to 0.34 ng/dL. Symptoms of hoarseness and neck swelling were already evident 4 months prior at which time tests for normal thyroid function were performed. The patient was referred due to aggravated pain on his diffusely enlarged hard goiter. An enlarged thyroid with some calcification was noticed in the neck ultrasonography with multiple cervical lymphadenopathies. Core biopsy of the thyroid gland showed invasion of poorly differentiated adenocarcinoma cells. Immunohistochemical studies showed positive staining only for carcinoembryonic antigen (CEA). There were multiple lung parenchymal nodules and adrenal masses at the time of evaluation. The patient was started on palliative chemotherapy with thyroid hormone replacement and gradually became euthyroid. From these findings and the clinical observations, thyroid metastasis with hypothyroidism developing acutely from metastatic colon adenocarcinoma was diagnosed.

Adenocarcinoma↗

PubMed2005

Doxorubicin prevents endoplasmic reticulum stress-induced apoptosis.

Several cellular stress signaling pathways initiate apoptosis in eukaryotic cells, but the interactions and coordination between the pathways have not been elucidated. In this study, apoptosis was triggered in MCF7 human breast carcinoma cells using doxorubicin, a topoisomerase inhibitor, and an endoplasmic reticulum (ER) stress inducer, thapsigargin, the latter causing the unfolded protein response (UPR). Interestingly, compared to treatment with doxorubicin or thapsigargin alone, cell death was reduced by treatment with both stress inducers. In contrast to another topoisomerase inhibitor, etoposide, doxorubicin markedly decreased apoptosis induced by thapsigargin; this doxorubicin effect was accompanied by reduced expression of the UPR-specific proapoptotic protein, C/EBP-homologous protein, and its upstream transcription factor, ATF4. We further found that doxorubicin downregulates the expression of ATF4 mRNA, indicating that doxorubicin interferes with the UPR at the level of ATF4 transcription. Taken together, the data suggest that ER stress-initiated cell death might be regulated by doxorubicin.

Activating Transcription Factor 4↗

PubMed2005

Renal ischemia/reperfusion injury activates the enhancer domain of the human cytomegalovirus major immediate early promoter.

Reactivation of latent human cytomegalovirus is of significant concern in immunocompromised transplant patients and is likely to occur through transcriptional activation of immediate early (ie) gene expression through mechanisms that are not well understood. TNF-mediated activation of NF-kappaB has been proposed to be one pathway leading to transcriptional activation of CMV ie gene expression. Using transgenic mice carrying a lacZ reporter gene under the control of the HCMV major ie promoter/enhancer (MIEP-lacZ mice) and MIEP-lacZ mice deficient in TNF receptor 1 and TNF receptor 2 (MIEP-lac Z TNFR DKO mice), we demonstrate that renal ischemia/reperfusion (I/R) injury activates the HCMV enhancer independently of TNF. Induction of MIEP-lacZ expression was preceded by TNFR-independent formation of reactive oxygen species (ROS), weak and transient activation of NF-kappaB and strong and sustained activation of AP-1. Our studies show that, in addition to TNF-mediated signaling, TNF-independent signaling induced by I/R injury can contribute to the activation of the HCMV enhancer. This likely occurs through ROS-mediated activation of AP-1. Targeting MAP kinase signaling pathways as well as NF-kappaB may be of therapeutic value in patients with CMV infection.

Animals↗

PubMed2005

M3 subtype of muscarinic receptors mediate Ca2+ release from intracellular stores in rat prostate neuroendocrine cells.

Our previous studies document the expression of adrenoceptors and purinoceptors in the rat prostate neuroendocrine cells (RPNECs). However, a direct investigation of the receptors for acetylcholine (ACh) is still lacking in the prostate neuroendocrine cells. RPNECs were freshly isolated from the ventral lobes of rat prostate by using collagenase. Effects of ACh and various muscarinic antagonists on the intracellular Ca(2+) concentration ([Ca(2+)](c)) were investigated by using the fura-2 spectrofluorimetry. Single-cell RT-PCR analysis was applied to identify the transcripts for the muscarinic receptor subtypes. ACh (5 microM) induced a sharp transient increase in the [Ca(2+)](c) of RPNECs, which was independent of the extracellular Ca(2+). In the same RPNECs, high KCl (60 mM), phenylephrine (5 microM), UTP (P2Y(1/2) agonist, 50 microM), and alpha, beta-meATP (P2X(1/3) agonist, 0.5 microM) also increased the [Ca(2+)](c). The ACh-induced [Ca(2+)](c) change (delta [Ca(2+)](c)) was blocked by atropine or by para-fluorohexahydrosiladifenidol (M(3) antagonist, 0.3 microM), but not by telenzepine (M(1) antagonist, 1 microM) and himbacine (M(2) and M(4) antagonist, 1 microM). The single-cell RT-PCR demonstrated the selective expression of mRNAs for M(3) in RPNECs. In summary, RPNECs express M(3) muscarinic receptors that are linked to the release of Ca(2+) from intracellular stores. The Ca(2+) signals of RPNECs might mediate the parasympathetic regulation of prostate gland.

Acetylcholine↗

PubMed2002

Enhanced detection and characterization of protocatechuate 3,4-dioxygenase in Acinetobacter lwoffii K24 by proteomics using a column separation.

Acinetobacter lwoffii K24 known as an aniline degrading bacterium has also been found to utilize p-hydroxybenzoate as a sole carbon source. In this study, 2-DE using Q-Sepharose column separation was attempted for fast screening of protocatechuate 3,4-dioxygenase for catabolism of p-hydroxybenzoate in A. lwoffii K24. Two protocatechuate 3,4-dioxygenase subunits, pcaG and pcaH were detected and identified with N-terminal and internal sequencing, suggesting proteomics using a column separation may be helpful for the identification of specific protein spots and maximizing the detectable protein spots on the 2-DE gel. The PCR process using degenerate primers for protocatechuate 3,4-dioxygenase and sequence analyses of the PCR products revealed the existence of pcaH and pcaG in A. lwoffii K24. These two subunits were found to be closely located and share extensive homology with pcaH and pcaG of Pseudomonas marginata or Pseudomonas cepacia, providing the evidence that A. lwoffi K24 has the protocatechuate branches as well as catechol branches of beta-ketoadipate pathway.

Acinetobacter↗

PubMed2002

Signal sequences control gating of the protein translocation channel in a substrate-specific manner.

N-terminal signal sequences mediate targeting of nascent chains to the endoplasmic reticulum and facilitate opening of the protein translocation channel to the passage of substrate. We have assessed each of these steps for a diverse set of mammalian signals. While minimal differences were seen in their targeting function, signal sequences displayed a remarkable degree of variation in initiating nascent chain access to the lumenal environment. Such substrate-specific properties of signals were evolutionarily conserved, functionally matched to their respective mature domains, and important for the proper biogenesis of some proteins. Thus, the sequence variations of signals do not simply represent functional degeneracy, but instead encode critical differences in translocon gating that are coordinated with their respective passengers to facilitate efficient translocation.

3T3 Cells↗

PubMed2002

Evaluation of facial skin type by sebum secretion: discrepancies between subjective descriptions and sebum secretion.

BACKGROUND/AIMS: Facial skin is usually classified as dry, normal, and oily in the cosmetics field. However, there is no standard objective method for classifying facial skin. METHODS: We measured sebum excretion with Sebumeter at four sites on the face. Based on the amount of sebum secretion, we reclassified skin type according to the guidelines provided by the manufacturer. The mean of sebum excretion (mean facial sebum excretion; MFSE) was also calculated. RESULTS: People secrete varying amounts of sebum at different skin sites. Reclassification of skin type based on sebum secretion revealed that most participants underestimated the amount of facial sebum excretion. When sebum secretion amounts were compared, a statistically significant difference was apparent between the oily and dry skin types. However, there were no statistical differences between oily and normal, and normal and dry skin. CONCLUSION: We showed that subjective skin type does not match the amount of sebum secreted. Thus, this simple and subjective classification is of very limited use and it should be re-evaluated by using an objective and standardized measuring tool.

Adult↗

PubMed2002

Cotranslational partitioning of nascent prion protein into multiple populations at the translocation channel.

The decisive events that direct a single polypeptide such as the prion protein (PrP) to be synthesized at the endoplasmic reticulum in both fully translocated and transmembrane forms are poorly understood. In this study, we demonstrate that the topological heterogeneity of PrP is determined cotranslationally, while at the translocation channel. By evaluating sequential intermediates during PrP topogenesis, we find that signal sequence-mediated initiation of translocation results in an interaction between nascent PrP and endoplasmic reticulum chaperones, committing the N terminus to the lumen. Synthesis of the transmembrane domain before completion of this step allows it to direct the generation of (Ctm)PrP, a transmembrane form with its N terminus in the cytosol. Thus, segregation of nascent PrP into different topological configurations is critically dependent on the precise timing of signal-mediated initiation of N-terminus translocation. Consequently, this step could be experimentally tuned to modify PrP topogenesis, including complete reversal of the elevated (Ctm)PrP caused by disease-associated mutations in the transmembrane domain. These results delineate the sequence of events involved in PrP biogenesis, explain the mechanism of action of (Ctm)PrP-favoring mutations associated with neurodegenerative disease, and more generally, reveal that translocation substrates can be cotranslationally partitioned into multiple populations at the translocon.

Amino Acid Sequence↗