The Indonesian Biomedical Journal

129-42

Authors: Anna Meiliana, Nurrani Mustika Dewi, Andi Wijaya

BACKGROUND: Aging per se is a risk factor for reduced cardiac function and heart diseases, even when adjusted for aging-associated cardiovascular risk factors. Accordingly, aging-related biochemical and cell-biological changes lead to pathophysiological conditions, especially reduced heart function and heart disease. CONTENT: Telomere dysfunction induces a profound p53-dependent repression of the master regulators of mitochondrial biogenesis and function, peroxisome proliferator-activated receptor gamma coactivator (PGC)-1a and PGC-1b in the heart, which leads to bioenergetic compromise due to impaired oxidative phosphorylation and ATP generation. This telomere-p53-PGC mitochondrial/ metabolic axis integrates many factors linked to heart aging including increased DNA damage, p53 activation, mitochondrial, and metabolic dysfunction and provides a molecular basis of how dysfunctional telomeres can compromise cardiomyocytes and stem cell compartments in the heart to precipitate cardiac aging. SUMMARY: The aging myocardium with telomere shortening and accumulation of senescent cells restricts the tissue regenerative ability, which contributes to systolic or diastolic heart failure. Moreover, patients with ion channel defects might have genetic imbalance caused by oxidative stress-related accelerated telomere shortening, which may subsequently cause sudden cardiac death. Telomere length can serve as a marker for the biological status of previous cell divisions and DNA damage with inflammation and oxidative stress. It can be integrated into current risk prediction and stratification models for cardiovascular diseases and can be used in precise personalized treatments.

147-52

Authors: Siska Mayasari Lubis, Miswar Fattah, Harun Alrasyid Damanik, Jose Rizal Latief Batubara

BACKGROUND: Childhood obesity is associated with the risk of adult obesity and obesity-related chronic disease. The fat mass and obesity-associated gene (FTO) rs9939609 variant are of particular interest because of its association with body mass index (BMI) and obesity-related phenotypes. This study was conducted to investigate the association between FTO gene rs9939609 variant with early onset obesity among Bataknese and Chinese children in Medan, Sumatera Utara, Indonesia. METHODS: The case-control study was carried out at 10 elementary schools in Medan. There were 212 children recruited; 56 early onset obesity and 61 control Bataknese and 49 early onset obesity and 46 control Chinese children. This study included a questionnaire, anthropometric measurements, and blood test analysis. rs9939609 polymorphism genotyping was performed using RT-PCR. Logistic regression, odds ratio (OR) and 95% confidence interval (CI) were calculated to determine the risk of obesity associated with the risk alleles, p<0.05 was considered as statistically significant. RESULTS: This study found a significant association between rs9939609 and early onset obesity in Chinese children(p=0.01), but not in Bataknese. The frequency of AA genotype was lower in the early onset obesity than in the normal weight children, while an OR of 0.69 showed that this genotype may protect against weight gaining and that the TT genotype may predispose to obesity. CONCLUSION: We concluded that the FTO gene rs9939609 is associated with early onset obesity in Chinese ethnicity but not in Bataknese.

160-4

Authors: Ferry Sandra, Karina Febriani Hudono, Amelia Astriani Putri, Chantika Amardhia Paramita Putri

BACKGROUND: Caffeic acid has been shown to induce apoptosis in MG63 osteosarcoma cells. Along with the apoptotic induction, caffeic acid was shown to activate caspase-8, -9 and -3. However, the role of caspase in mediating caffeic acid-induced apoptosis in MG63 cells are not clear yet. In this study, caspase role was further investigated by inhibiting caspase activity in the caffeic acid-induced apoptosis system in the MG63 cells. METHODS: MG63 cells were cultured, starved, pretreated with/without Z-VAD FMK and treated with/without 10 μg/mL caffeic acid. To quantify the number of apoptotic MG63 cells, Sub-G1 method was performed. The caffeic acid-induced apoptotic morphology was confirmed with 4',6-diamidino-2-phenylindole (DAPI) staining and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. Meanwhile, to detect apoptotic underlying mechanism, immunoblotting was performed to detect caspase-8, -9 and -3. RESULTS: The MG63 cells were significantly induced into apoptosis with the treatment of 10 μg/mL caffeic acid for 48 hours. However, pretreatment of 100 μM Z-VAD-FMK, a pan caspase inhibitor, for 2 hours, the percentage of apoptotic MG63 cells was significantly diminished. The apoptotic phenomenon induced by caffeic acid as well as the inhibition of Z-VAD-FMK were confirmed by DAPI staining and TUNEL assay. Cleaved caspase-8, -9 and -3 were formed markedly upon the treatment of caffeic acid. Pretreatment of 100 μM Z-VAD-FMK could inhibit the cleaved caspase-8, -9 and -3. CONCLUSION: Taken together, caffeic acid has the potential to induce apoptosis in MG63 cells, specifically through the caspase signaling pathway.