1.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
2.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
3.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
4.Shank3 Overexpression Leads to Cardiac Dysfunction in Mice by Disrupting Calcium Homeostasis in Cardiomyocytes
Tae Hee KO ; Yoonhee KIM ; Chunmei JIN ; Byeongil YU ; Minju LEE ; Phuong Kim LUONG ; Tran Nguyet TRINH ; Yeji YANG ; Hyojin KANG ; Yinhua ZHANG ; Ruiying MA ; Kwangmin YOO ; Jungmin CHOI ; Jin Young KIM ; Sun-Hee WOO ; Kihoon HAN ; Jong-Il CHOI
Korean Circulation Journal 2025;55(2):100-117
Background and Objectives:
SH3 and multiple ankyrin repeat domains 3 (Shank3) proteins play crucial roles as neuronal postsynaptic scaffolds. Alongside neuropsychiatric symptoms, individuals with SHANK3 mutations often exhibit symptoms related to dysfunctions in other organs, including the heart. However, detailed insights into the cardiac functions of Shank3 remain limited. This study aimed to characterize the cardiac phenotypes of Shank3-overexpressing transgenic mice and explore the underlying mechanisms.
Methods:
Cardiac histological analysis, electrocardiogram and echocardiogram recordings were conducted on Shank3-overexpressing transgenic mice. Electrophysiological properties, including action potentials and L-type Ca2+ channel (LTCC) currents, were measured in isolated cardiomyocytes. Ca2+ homeostasis was assessed by analyzing cytosolic Ca2+transients and sarcoplasmic reticulum Ca2+ contents. Depolarization-induced cell shortening was examined in cardiomyocytes. Immunoprecipitation followed by mass spectrometrybased identification was employed to identify proteins in the cardiac Shank3 interactome.Western blot and immunocytochemical analyses were conducted to identify changes in protein expression in Shank3-overexpressing transgenic cardiomyocytes.
Results:
The hearts of Shank3-overexpressing transgenic mice displayed reduced weight and increased fibrosis. In vivo, sudden cardiac death, arrhythmia, and contractility impairments were identified. Shank3-overexpressing transgenic cardiomyocytes showed prolonged action potential duration and increased LTCC current density. Cytosolic Ca2+ transients were increased with prolonged decay time, while sarcoplasmic reticulum Ca2+ contents remained normal. Cell shortening was augmented in Shank3-overexpressing transgenic cardiomyocytes. The cardiac Shank3 interactome comprised 78 proteins with various functions. Troponin I levels were down-regulated in Shank3-overexpressing transgenic cardiomyocytes.
Conclusions
This study revealed cardiac dysfunction in Shank3-overexpressing transgenic mice, potentially attributed to changes in Ca2+ homeostasis and contraction, with a notable reduction in troponin I.
5.Relationship between long-term PM2.5 exposure and myopia prevalence in adults: analysis of the Korea National Health and Nutrition Examination Survey–Air Pollution Linked Data, 2020
Minju JUNG ; Hyungdoo KIM ; Ji Hoon KIM ; Dong-Jae SEO ; Jong-Han LEEM ; Shin-Goo PARK ; Dong-Wook LEE ; Hwan-Cheol KIM
Annals of Occupational and Environmental Medicine 2025;37(1):e8-
Background:
PM2.5 (particulate matter less than 2.5 μm) causes various health problems. Recent studies suggest that long-term exposure to PM2.5 may have a negative impact on vision. This study examined the effects of long-term exposure to concentrations of PM2.5 exceeding Korean standards on myopia prevalence.
Methods:
This study was conducted on adults aged 40–69 years. The PM2.5 concentrations were calculated as the 1–5-year moving averages based on the participants' residential areas. The relationships between the PM2.5 levels, categorized by the annual average concentration standard in Korea, and the prevalence of myopia were analyzed using binary logistic regression. The results were evaluated using the 95% confidence interval.
Results:
PM2.5 concentrations averaged over 1–3 years were not significantly associated with the prevalence of myopia. On the other hand, the prevalence of myopia was significantly higher in areas where the 4–5-year moving average PM2.5 levels exceeded the Korean standards. These findings suggest that long-term exposure to PM2.5 may have a detrimental effect on vision.
Conclusions
This study revealed the impact of long-term PM2.5 exposure on the prevalence of myopia, highlighting the importance of managing PM2.5 levels. Nevertheless, further cohort studies focusing on adults and in-depth research into the effects of long-term exposure will be necessary.
6.Association of weight and dietary habits with high blood mercury levels in Korean adolescents: data from the KoNEHS cycle 4, 2018-2020
Ji Hoon KIM ; Minju JUNG ; Jaewon MUN ; Dong-Jae SEO ; Jong-Han LEEM ; Shin-Goo PARK ; Dong-Wook LEE ; Hyung Doo KIM ; Hwan-Cheol KIM
Annals of Occupational and Environmental Medicine 2025;37(1):e5-
Background:
Humans are exposed to mercury primarily in its highly toxic form, methyl mercury, which is known to have adverse effects on various organs and systems. The negative impact of mercury exposure on the growth, development, and mental health of children, from infancy to adolescence, is well-documented. However, there are no internationally standardized safe limits for mercury exposure. This study investigated the impact of dietary habits and higher body mass index (BMI) on blood mercury levels in adolescents.
Methods:
This study analyzed the data from the 4th Korean National Environmental Health Survey (KoNEHS) 2018–2020. The focus was on 825 middle and high school students aged 13–18 years, whose blood mercury levels were measured. A survey on dietary and lifestyle habits was also conducted. Blood mercury levels were categorized by geometric median values, and associations with overweight status and seafood consumption were examined using a generalized linear model.
Results:
The geometric mean blood mercury level for the entire sample was 1.37 μg/L, with levels of 1.31 μg/L in normal-weight individuals and 1.43 μg/L in overweight individuals, showing a statistically significant difference between the two groups. After adjusting for other variables, blood mercury levels were significantly associated with overweight status (estimate: 0.084; p = 0.018; 95% confidence interval [CI]: 0.015–0.153), consumption of large fish and tuna more than once a week (estimate: 0.18; p = 0.001; 95% CI: 0.077–0.284), and consumption of fish once a week or more (estimate: 0.147; p = 0.004; 95% CI: 0.043–0.250).
Conclusions
In adolescents, a higher BMI and an increased consumption of large fish, tuna, and fish were associated with higher blood mercury levels. Notably, a stronger association was found between large fish consumption and blood mercury levels in the overweight group. These findings suggest the need to moderate seafood consumption and establish more proactive mercury exposure standards for adolescents.
7.Normative Parameters of Olfactory Bulbs Based on Magnetic Resonance Imaging and Olfactory Function
Minju KIM ; Ji Ye LEE ; Yong Hwy KIM ; Seung Hong CHOI ; Tae-Bin WON ; Doo Hee HAN
Journal of Korean Medical Science 2024;39(45):e321-
Background:
Olfactory dysfunction is a frequently encountered sensory disorder that increases with aging, assessed magnetic resonance imaging (MRI); however, reference quantitative values for associated anatomical structures have rarely been suggested. The aim of this study was to assess the parameters of the olfactory bulbs (OBs) and olfactory sulcus (OS) in Korean adults according to age, along with their olfactory function.
Methods:
We retrospectively evaluated 217 consecutive patients (104 men, 113 women;mean age, 52.4 ± 15.6 years) who underwent sellar MRI and olfactory function testing before transsphenoidal approach at a single tertiary center from March 2022 to December 2023. Based on the T2-weighted MRI, we evaluated the quantitative size parameters and morphological features of patients’ OB and OS, along with their olfactory function test scores. We assessed the relationship between OB volume and age in pairwise correlations.
Results:
The mean OB volume was 45.6 ± 15.3 mm 3 in all patients. The patients’ mean Korean version of the Sniffin’ Sticks (KVSS) test II score was 26.8 ± 4.1. OB volume (P < 0.001), height (P < 0.001), and anteroposterior diameter (APD) (P < 0.001) differed significantly among the different age groups. Reduced OB volume was significantly associated with aging (r = –0.58, P < 0.001) and a decline in olfactory function scores (r = 0.34, P < 0.001).
Conclusion
Based on MRI, we proposed reference OB and OS values in adults of different age groups, highlighting the reduction in OB parameters, especially height and APD along with volume associated with aging and olfactory decline. These values can be useful for evaluating adult patients undergoing MRI for olfactory dysfunction.
8.Normative Parameters of Olfactory Bulbs Based on Magnetic Resonance Imaging and Olfactory Function
Minju KIM ; Ji Ye LEE ; Yong Hwy KIM ; Seung Hong CHOI ; Tae-Bin WON ; Doo Hee HAN
Journal of Korean Medical Science 2024;39(45):e321-
Background:
Olfactory dysfunction is a frequently encountered sensory disorder that increases with aging, assessed magnetic resonance imaging (MRI); however, reference quantitative values for associated anatomical structures have rarely been suggested. The aim of this study was to assess the parameters of the olfactory bulbs (OBs) and olfactory sulcus (OS) in Korean adults according to age, along with their olfactory function.
Methods:
We retrospectively evaluated 217 consecutive patients (104 men, 113 women;mean age, 52.4 ± 15.6 years) who underwent sellar MRI and olfactory function testing before transsphenoidal approach at a single tertiary center from March 2022 to December 2023. Based on the T2-weighted MRI, we evaluated the quantitative size parameters and morphological features of patients’ OB and OS, along with their olfactory function test scores. We assessed the relationship between OB volume and age in pairwise correlations.
Results:
The mean OB volume was 45.6 ± 15.3 mm 3 in all patients. The patients’ mean Korean version of the Sniffin’ Sticks (KVSS) test II score was 26.8 ± 4.1. OB volume (P < 0.001), height (P < 0.001), and anteroposterior diameter (APD) (P < 0.001) differed significantly among the different age groups. Reduced OB volume was significantly associated with aging (r = –0.58, P < 0.001) and a decline in olfactory function scores (r = 0.34, P < 0.001).
Conclusion
Based on MRI, we proposed reference OB and OS values in adults of different age groups, highlighting the reduction in OB parameters, especially height and APD along with volume associated with aging and olfactory decline. These values can be useful for evaluating adult patients undergoing MRI for olfactory dysfunction.
9.Effect of job satisfaction on depression after adjusting for satisfaction with other life domains
SeongCheol YANG ; Ji Hoon KIM ; Minju JUNG ; Hwan-Cheol KIM ; Jong-Han LEEM ; Shin-Goo PARK
Annals of Occupational and Environmental Medicine 2024;36(1):e8-
Studies on the association between job satisfaction and depression have often been reported. However, no study has examined how job satisfaction impacts depression while considering satisfaction with other aspects of life. In this study, we evaluated the effect of job satisfaction on depression after adjusting for satisfaction with other domains of life. We used data from the 16th wave of the Korean Welfare Panel Study. A total of 3568 current employees without depression who completed a survey were included. Depression was measured using the abbreviated version of the CES-D scale. Various types of satisfaction, including job satisfaction, were measured using single-item questions and a 5-point Likert scale. The association between job satisfaction and depression after considering satisfaction with other life domains was analyzed using a multiple logistic regression model. Crude models showed a significant association between job satisfaction and depression in males (odds ratio [OR]: 7.90; 95% confidence interval [CI]: 4.11–15.23) and females (OR: 7.12; 95% CI: 4.40–11.50). When adjusted for sociodemographic factors, health-related factors, and work-related factors, the association remained significant in males (OR: 6.20; 95% CI: 3.10–12.41) and females (OR: 6.28; 95% confidence interval (CI): 3.79–10.40). However, when satisfaction with other life domains was included, the association remained significant only in females (OR: 3.55; 95% CI: 1.93–6.50). This study shows an association between job satisfaction and depression in Korean employees. However, when satisfaction with other life domains was considered, this association remained significant only in women. Regular screening of job satisfaction should be considered as a means of preventing and managing depression among female employees.
10.Normative Parameters of Olfactory Bulbs Based on Magnetic Resonance Imaging and Olfactory Function
Minju KIM ; Ji Ye LEE ; Yong Hwy KIM ; Seung Hong CHOI ; Tae-Bin WON ; Doo Hee HAN
Journal of Korean Medical Science 2024;39(45):e321-
Background:
Olfactory dysfunction is a frequently encountered sensory disorder that increases with aging, assessed magnetic resonance imaging (MRI); however, reference quantitative values for associated anatomical structures have rarely been suggested. The aim of this study was to assess the parameters of the olfactory bulbs (OBs) and olfactory sulcus (OS) in Korean adults according to age, along with their olfactory function.
Methods:
We retrospectively evaluated 217 consecutive patients (104 men, 113 women;mean age, 52.4 ± 15.6 years) who underwent sellar MRI and olfactory function testing before transsphenoidal approach at a single tertiary center from March 2022 to December 2023. Based on the T2-weighted MRI, we evaluated the quantitative size parameters and morphological features of patients’ OB and OS, along with their olfactory function test scores. We assessed the relationship between OB volume and age in pairwise correlations.
Results:
The mean OB volume was 45.6 ± 15.3 mm 3 in all patients. The patients’ mean Korean version of the Sniffin’ Sticks (KVSS) test II score was 26.8 ± 4.1. OB volume (P < 0.001), height (P < 0.001), and anteroposterior diameter (APD) (P < 0.001) differed significantly among the different age groups. Reduced OB volume was significantly associated with aging (r = –0.58, P < 0.001) and a decline in olfactory function scores (r = 0.34, P < 0.001).
Conclusion
Based on MRI, we proposed reference OB and OS values in adults of different age groups, highlighting the reduction in OB parameters, especially height and APD along with volume associated with aging and olfactory decline. These values can be useful for evaluating adult patients undergoing MRI for olfactory dysfunction.

Result Analysis
Print
Save
E-mail