Biomedical subjects

Hyungsoo Kim

Publications and source records attributed to Hyungsoo Kim.

18 recordsLinked to original sources

PubMed2007

Hydrogen peroxide triggers the proteolytic cleavage and the inactivation of calcineurin.

Increases in the levels of reactive oxygen species (ROS) are correlated with a decrease in calcineurin (CN) activity under oxidative or neuropathological conditions. However, the molecular mechanism underlying this ROS-mediated CN inactivation remains unclear. Here, we describe a mechanism for the inactivation of CN by hydrogen peroxide. The treatment of mouse primary cortical neuron cells with Abeta(1-42) peptide and hydrogen peroxide triggered the proteolytic cleavage of CN and decreased its enzymatic activity. In addition, hydrogen peroxide was found to cleave CN in different types of cells. Calcium influx was not involved in CN inactivation during hydrogen peroxide-mediated cleavage, but CN cleavage was partially blocked by chloroquine, indicating that an unidentified lysosomal protease is probably involved in its hydrogen peroxide-mediated cleavage. Treatment with hydrogen peroxide triggered CN cleavage at a specific sequence within its catalytic domain, and the cleaved form of CN had no enzymatic ability to dephosphorylate nuclear factor in activated T cells. Thus, our findings suggest a molecular mechanism by which hydrogen peroxide inactivates CN by proteolysis in ROS-related diseases.

Amyloid beta-Peptides↗

PubMed2006

Cabin1 represses MEF2 transcriptional activity by association with a methyltransferase, SUV39H1.

Myocyte enhancer factor 2 (MEF2) plays pivotal roles in various biological processes, and its transcriptional activity is regulated by histone acetylation/deacetylation enzymes in a calcium-dependent fashion. A calcineurin-binding protein 1 (Cabin1) has been shown to participate in repression of MEF2 by recruiting mSin3 and its associated histone deacetylases. Here, we report that histone methylation also takes a part in Cabin1-mediated repression of MEF2. Immunoprecipitate of Cabin1 complex can methylate histone H3 by association with SUV39H1. SUV39H1 increased Cabin1-mediated repression of MEF2 transcriptional activity in MEF2-targeting promoters. The SUV39H1 was revealed to bind to the 501-900-amino acid region of Cabin1, which was distinct from its histone deacetylase-recruiting domain. In addition, the Gal4-Cabin1-(501-900) alone repressed a constitutively active Gal4-tk-promoter, indicating that Cabin1 recruits SUV39H1 and represses transcriptional activity. Finally, both SUV39H1 and Cabin1 were shown to bind on the MEF2 target promoter in a calcium-dependent manner. Thus, Cabin1 recruits chromatin-modifying enzymes, both histone deacetylases and a histone methyltransferase, to repress MEF2 transcriptional activity.

Amino Acids↗

PubMed2006

A novel function of Nur77: physical and functional association with protein kinase C.

Despite the involvement in diverse physiological process and pleiotropic expression profile, the molecular functions of Nur77 are not likely to be fully elucidated. From the effort to find a novel function of Nur77, we detected molecular interaction between Nur77 and PKC. Details of interaction revealed that C-terminal ligand binding domain (LBD) of Nur77 specifically interacted with highly conserved glycine-rich loop of PKC required for catalytic activity. This molecular interaction resulted in inhibition of catalytic activity of PKCtheta by Nur77. C-terminal LBD of Nur77 is sufficient for inhibiting the phosphorylation of substrate by PKCtheta. Ultimately, inhibition of catalytic activity by Nur77 is deeply associated with repression of PKC-mediated activation of AP-1 and NF-kappaB. Therefore, these findings demonstrate a novel function of Nur77 as a PKC inhibitor and give insights into molecular mechanisms of various Nur77-mediated physiological phenomena.

Animals↗

PubMed2006

p53 stabilization and transactivation by a von Hippel-Lindau protein.

von Hippel-Lindau (VHL) disease is a rare autosomal dominant cancer syndrome. Although hypoxia-inducible factor-alpha (HIFalpha) is a well-documented substrate of von Hippel-Lindau tumor suppressor protein (pVHL), it remains unclear whether the dysregulation of HIF is sufficient to account for de novo tumorigenesis in VHL-deleted cells. Here we found that pVHL directly associates with and stabilizes p53 by suppressing Mdm2-mediated ubiquitination and nuclear export of p53. Moreover, upon genotoxic stress, pVHL invoked an interaction between p53 and p300 and the acetylation of p53, which ultimately led to an increase in p53 transcriptional activity and p53-mediated cell cycle arrest and apoptosis. These results suggest that the tumor suppressor pVHL has an unexpected function to upregulate the tumor suppressor p53.

Acetylation↗

PubMed2006

The impact of comorbidity on wealth changes in later life.

OBJECTIVES: Despite the high prevalence of comorbidity in later life, scientists do not fully understand its financial impact. The objective of this study was to enhance researchers' understanding of the impact of compounded health problems on the wealth of older people. METHODS: Using data from the Asset and Health Dynamics Among the Oldest Old study (1995 to 2002 waves), we conducted ordinary least squares regression analysis on wealth changes. RESULTS: We found that comorbidity leads to significant wealth depletion in later life, especially for single elders. Single elders with comorbidity depleted 20% to 22% of their wealth over a 2- to 3-year time period, especially those with the combination of heart disease and diabetes. The impact of comorbidity was disproportionately greater than the estimated impact of a single health problem. However, the impact of comorbidity did not appear to be significant among married people. DISCUSSION: We found that compounded health problems also create compounded financial problems in later life. For an accurate estimation of the financial consequences of health problems, it is important to consider comorbid health problems, as the effect of comorbidity is not equal to the sum of the effects of single health problems.

Age Factors↗

PubMed2006

Driving cessation and consumption expenses in the later years.

OBJECTIVES: This study examined the association between consumption and driving status among older persons within the context of selected variables, including self-rated health and functional status. METHODS: The data were from the 1998, 2000, and 2002 Health and Retirement Study and the 2003 Health and Retirement Study Consumption and Activities Mail Survey. We conducted Tobit regression analyses on five consumption categories of basic needs (such as food) and higher order needs (such as trips and dining out). RESULTS: Consumption and driving status were significantly associated, showing that driving cessation was related to a 46% to 63% reduction in spending on trips, tickets, and dining out. Another significant relationship emerged between consumption and having never driven. Driving cessation was minimally related to consumption of basic needs (such as food and clothing) and was more strongly associated with higher order needs (such as trips). DISCUSSION: The findings demonstrate the association between older people's driving status and consumption, specifically higher order activities. Older persons who drive and, presumably, have more opportunities to go to stores, restaurants, and other outside events, spend more on food, tickets, and dining out than those who cease driving or have never driven. Although the direction of causality remains unclear, these findings have implications for those concerned with alternative transportation resources for older adults.

Aged↗

PubMed2006

Medicaid and family wealth transfer.

PURPOSE: This study examines whether the relationship between making familial wealth transfers and becoming a Medicaid recipient sheds light on the current debate about Medicaid estate planning, whereby some elders transfer their assets to their families to qualify for Medicaid. DESIGN AND METHODS: Using the Health and Retirement Study, we tracked a national sample of community-based elders who did not receive Medicaid at the 1993 baseline interview but became Medicaid recipients during a 10-year time period and examined wealth transfers for these new Medicaid beneficiaries. RESULTS: Among elders aged 70 or older who did not receive Medicaid in 1993, 16.4% became Medicaid recipients over 10 years. Among these new Medicaid recipients, 17.9% transferred their wealth to family members before receiving Medicaid benefits, with an average transfer amount of $8,507 during the 2 years prior to receiving Medicaid benefits. In addition, 15.2% of community-residing elders entered a nursing home during the 10-year period, and 26.3% of these were covered by Medicaid. Of these new Medicaid recipients living in nursing homes, 12.6% transferred wealth to their families in the mean amount of $4,112. IMPLICATIONS: Familial wealth transfers do occur before changes in Medicaid eligibility in a small, but nontrivial, number of cases, but the amount transferred is modest, especially among nursing home residents. This finding implies that policies to reduce Medicaid long-term-care expenditures by limiting such transfers may not be very effective.

Aged↗

PubMed2006

Older Women's Health and Its Impact on Wealth.

As many elderly women tend to outlive their spouses, there is a growing population of unmarried elderly women. Unmarried women are worse off than married women both financially and physically. A question that has not been answered is whether and how the relationship between health and wealth differs across elderly women's marital status. Do the negative impacts of health problems cause more serious financial consequences for unmarried elderly women than married women? Using the five waves of data from the Asset and Health Dynamics Among the Oldest Old (AHEAD) from 1993 to 2002, this question is empirically investigated. Results indicate that severe chronic conditions result in 4 to 10% greater wealth depletion for unmarried women than married women. This finding calls for heightened awareness of the negative financial consequences of health problems and also calls for increased lifetime earning potential, reconsideration of women's retirement benefits, and greater attention to preventive care.

Activities of Daily Living↗

PubMed2005

Menin represses JunD transcriptional activity in protein kinase C theta-mediated Nur77 expression.

TCR signaling leading to thymocyte apoptosis is mediated through the expression of the Nur77 family of orphan nuclear receptors. It has been shown that the Nur77 promoter is activated by at least two signaling pathways, one mediated by calcium and the other by protein kinase C (PKC). MEF2D has been known to regulate Nur77 expression in a calcium- dependent manner. The mechanism by which calcium regulates MEF2D is through dissociation of calcium-sensitive MEF2 corepressors (Cabin1/HDACs, HDAC4/5) and the association with calcineurin-activated transcription factor NF-AT and the coactivator p300. However, little is known about how PKC activates the Nur77 promoter. Herein, we report that PKCtheta targets AP-1 like response element in the Nur77 promoter where JunD constitutively binds. PKCtheta triggers mitogen-activated protein kinase-inediated phosphorylation of JunD, and increases transcriptional activity of JunD, cooperatively with p300. Menin is identified as the transcriptional corepressor for JunD via recruitment of mSin3-istone deacetylases. In fact, Menin represses PKCtheta/p300-mediated transcriptional activity of JunD in T cell. Its dynamic regulation of histone modifiers with JunD is responsible for PKCq-synergistic effect on Nur77 expression in T cell.

Cell Line, Tumor↗

PubMed2005

Dynamic self-assembly of polymer colloids to form linear patterns.

A dynamic self-assembling process is reported which involves drying a droplet of positively charged colloidal suspension on a flat negatively charged hydrophilic surface. This extremely simple method affords lines of colloidal particles with regular 1.5-4.5 microm line spacing and smaller than 2 microm line width over a broad surface area. The ordered region diffracts light to display an iridescent appearance and generates first-order diffraction spots when illuminated by a He-Ne laser. A periodic stick-slip motion of the drying liquid front is observed during the drying process using optical microscopy. The periodic motion must be related to the periodic particle deposition. We propose that the simultaneous deposition of the particles at a fixed distance (i.e., the line spacing) behind the previous line of particles where the contact line is pinned is in turn responsible for the periodic stick-slip motion. The key distinguishing feature of the present system is the attractive interaction between the particles and the surface, which instigates the periodicity of the particle deposition.

Journal Article↗

PubMed2005

Oxidative stress attenuates Fas-mediated apoptosis in Jurkat T cell line through Bfl-1 induction.

Many types of mammalian cells produce ROS in response to many different stimuli to modulate a number of cellular functions, including apoptosis. However, the correlation between ROS and apoptosis remains controversial, and the mechanisms whereby ROS-induced signals are propagated to critical downstream targets remain largely undefined. Here, we demonstrate that hydrogen peroxide (H2O2) upregulates the expression of Bfl-1, an antiapoptotic member of the Bcl-2 family, and that this is responsible for the antiapoptotic activity of ROS. When Jurkat, human leukemic T cells, were pretreated with 100 microM H2O2 and then treated with anti-Fas antibody, apoptosis was impaired without change of cell surface Fas expression. An investigation of the expression patterns of Bcl-2 family genes revealed that H2O2 treatment induced Bfl-1 gene expression, but left other genes unchanged, and this Bfl-1 expression and H2O2 -induced antiapoptotic effect was inhibited by antioxidants or NF-kappaB inhibitor. In addition, an electromobility shift assay revealed that the p65/p50 subunits of NF-kappaB activated by H2O2 bound to a bfl-1 promoter. Neither the induction of Bfl-1 nor the antiapoptotic effect of H2O2 was detected in Bfl-1-knockdown Jurkat cell line containing Bfl-1 antisense (Bfl-1AS). These data indicate that oxidative stress induces the expression of Bfl-1 via NF-kappaB activation, and this early-response gene protects cells from Fas-mediated apoptosis. This may be a cellular survival mechanism of cells exposed to phagocytes-derived ROS.

Acetylcysteine↗

PubMed2005

Gender differences in polysomnographic sleep in young healthy sleepers.

Middle-aged and elderly populations exhibit gender differences in polysomnographic (PSG) sleep; however, whether young men and women also show such differences remains unclear. Thirty-one young healthy sleepers (16 men and 15 women, aged 18 to 30 yr, mean+/-SD, 20.5+/-2.4 yr) completed 3 consecutive overnight sessions in a sleep laboratory, after maintaining a stable sleep-wake cycle for 1 wk before study entry. Standard PSG sleep and self-rated sleepiness data were collected each night. Across nights, women showed better sleep quality than men: they fell asleep faster (shorter sleep onset latency) and had better sleep efficiency, with more time asleep and less time awake (all differences showed large effect sizes, d=0.98 to 1.12). By contrast, men were sleepier than women across nights. Both men and women demonstrated poorer overall sleep quality on the first night compared with the subsequent 2 nights of study. We conclude young adult healthy sleepers show robust gender differences in PSG sleep, like older populations, with better sleep quality in women than in men. These results highlight the importance of gender in sleep and circadian rhythm research studies employing young subjects and have broader implications for women's health issues relating to these topics.

Adolescent↗

PubMed2005

An olfactory stimulus modifies nighttime sleep in young men and women.

Aromatherapy is an anecdotal method for modifying sleep and mood. However, whether olfactory exposure to essential oils affects night-time objective sleep remains untested. Previous studies also demonstrate superior olfactory abilities in women. Therefore, this study investigated the effects of an olfactory stimulus on subsequent sleep and assessed gender differences in such effects. Thirty-one young healthy sleepers (16 men and 15 women, aged 18 to 30 yr, mean+/-SD, 20.5+/-2.4 yr) completed 3 consecutive overnight sessions in a sleep laboratory: one adaptation, one stimulus, and one control night (the latter 2 nights in counterbalanced order). Subjects received an intermittent presentation (first 2 min of each 10 min interval) of an olfactory (lavender oil) or a control (distilled water) stimulus between 23:10 and 23:40 h. Standard polysomnographic sleep and self-rated sleepiness and mood data were collected. Lavender increased the percentage of deep or slow-wave sleep (SWS) in men and women. All subjects reported higher vigor the morning after lavender exposure, corroborating the restorative SWS increase. Lavender also increased stage 2 (light) sleep, and decreased rapid-eye movement (REM) sleep and the amount of time to reach wake after first falling asleep (wake after sleep onset latency) in women, with opposite effects in men. Thus, lavender serves as a mild sedative and has practical applications as a novel, nonphotic method for promoting deep sleep in young men and women and for producing gender-dependent sleep effects.

Adolescent↗

PubMed2005

Circadian phase determined from melatonin profiles is reproducible after 1 wk in subjects who sleep later on weekends.

The aim of this study was to determine whether circadian phase from salivary melatonin profiles is the same when measured in phase assessments 1 wk apart. Eleven healthy young men and women maintained a fixed, home sleep-wake schedule, in bed, in the dark 23:00-07:00 hr on weekdays. On Friday and Saturday nights they were permitted to wake up and go to bed up to 1 hr later, and on Saturdays and Sundays they could nap between 13:30 and 16:30 hr. The study was run in the summer. Subjects wore sunglasses when outside during the day, and went outside for at least 15 min between 08:00 and 09:00 hr each morning. They maintained this schedule for 15 days before the first assessment and the 6 days in between the two assessments. During the assessments subjects remained awake overnight in <5 lux and gave saliva samples every 30 min. A recovery nap (13:00-17:00 hr) followed the first session. The dim light melatonin onset (DLMO), offset (DLMOff) and midpoint were used as phase markers. There was minimal change in their timing between the two phase assessments. The average absolute change in midpoint (the change in phase regardless of direction) was 20 min. There was a small, 30 min delay in the DLMO. Thus, circadian phase can be measured a week in advance of any phase shifting intervention and, as long as the prescribed sleep and morning light schedule is maintained, the phase at the start of treatment can be confidently estimated.

Adult↗

PubMed2005

Unequal Effects of Elders' Health Problems on Wealth Depletion across Race and Ethnicity.

We investigate the impact of health on wealth depletion of African American, Hispanic, and non-Hispanic white elders. Using the data from 4,464 elderly households that participated in both the 1993 Asset and Health Dynamics of the Oldest Old and the 1998 Health and Retirement Study, we find that health problems contribute to wealth depletion differently across elders in different racial and ethnic groups. We draw policy implications from the findings regarding ways to help consumers protect their financial security from health shocks in later life.

Journal Article↗

PubMed2003

Menin, a tumor suppressor, represses JunD-mediated transcriptional activity by association with an mSin3A-histone deacetylase complex.

Menin, a gene product of multiple endocrine neoplasia type I (MEN1), is known to act as a tumor suppressor to repress JunD transcription factor. However, the mechanism by which Menin represses JunD transcriptional activity was still unclear. In this study, we found that Menin is a corepressor against JunD transcriptional activity via recruitment of histone deacetylases in an mSin3A-dependent manner. The amino acid search revealed that central domain of Menin includes a alpha-helical mSin3-interacting domain [SID (371-387)]. The SID mutation of Menin (L381P/A385P) abolished the interaction between mSin3A and paired amphipathic helix 2 domain of Menin and reduced its ability to repress JunD transcriptional activity, implicating that SID of Menin is important for recruiting an mSin3A-histone deacetylase complex to repress JunD transcriptional activity.

Amino Acid Sequence↗

PubMed2003

An examination of the impact of health on wealth depletion in elderly individuals.

OBJECTIVES: This study investigates the effects of new health events and existing health conditions on wealth depletion in elderly individuals. METHODS: A model deriving from life-cycle theory is proposed and estimated using Waves 1 and 2 of the Asset and Health Dynamics of the Oldest Old (AHEAD) data set. RESULTS: Both new health events and existing health conditions significantly influence wealth depletion of elders, but their impacts differ across marital status. Whereas an occurrence of new health events brought wealth depletion of elders in married households, having existing chronic health conditions was associated with wealth depletion of elders in single households. DISCUSSION: Poor health, both a new health event and existing chronic conditions, leads to considerable wealth depletion in elderly individuals. Considering the significant impacts of health on wealth, the public needs to be better informed of potential health events in later life and the associated financial burden. Additional health insurance plays an important role in preventing elders from financial hardship.

Aged↗

PubMedDate not supplied

Analysis of the effect of aging on the response to hypoxia by cDNA microarray.

Little is known about the detail of hypoxia-responsive gene expression patterns in advanced age, even though aging is thought to be partially associated with a decreased response to hypoxia. In the present study, we identified several hypoxia-inducible genes and investigated the effect of aging on hypoxic gene expression profiles using cDNA microarray analysis of young/old human diploid fibroblasts. Of 7458 genes in the microarray, we found that genes involved in angiogenesis, defense against oxidative stress, and transcription regulation are severely impaired in senescent cell, which is consistent with the fact that aged cells have attenuated responses to various stimuli.

Cells, Cultured↗