Agustina Tri Endharti

Genetic Variant of C-5434T REN Enhancer on Serum Renin Levels and Binding Pattern of Signal Transducers and Activators Transcription 3.

The human renin gene has been widely known to be involved in essential hypertension (EH) pathogenesis. Genetic variant C-5434T of REN enhancer contributed to renin gene transcription and serum renin regulation. However, the mechanism associated with the transcription level changes remains unknown, and only a few reports exist that discussed serum renin levels on C-5434T of REN. Thus, this study aims to investigate the relationship between genetic variant C-5434T of REN enhancer and serum renin levels in Indonesian hypertensive patients. SNP of C-5434T was genotyped in 56 hypertensive patients by using RFLP. The data showed that serum renin is slightly higher in hypertensive patients with the TT genotype (39 ± 10.3) than patients with the CC genotype (33 ± 10.6) but the difference was not statistically significant (p = 0.35). Here, we also present a docking approach for predicting interaction between genetic variant -5434C/T and STAT3 (Signal Transducers and Activators Transcription 3), the predicted transcription factor that regulates renin gene enhancer. The results showed that STAT3-DNA allele T more favorably binds to DNA than STAT3-DNA allele C. These data suggest that the presence of genetic variant C-5434T has changed the binding pattern of STAT3 to REN enhancer. This is likely to influence STAT3 activity to stimulate the expression of renin gene in producing renin.

Indonesian Pasuruan propolis extract does not exert antiproliferation and pro-apoptotic effect on human colon carcinoma cell line HT-29

Purpose : To evaluate the anti-cancer activity of Indonesian Pasuruan propolis extract (PPE) against HT-29 human colon carcinoma cell line. Methods : HT-29 cells were cultured and treated in different concentrations of PPE (50, 100, 200, 400 μg/mL) for 24 h. The cells were evaluated by several indicators such as cell proliferation and apoptosis as well as the expression of protein Ki67, p53, cyclin D1, and Bcl-xL. Results : Administration of PPE inhibited cell proliferation of HT-29 in concentration-dependent manner but the effect was not significant (p = 0.842); the results were similar with regard to the expression of Ki67 in HT-29 cells (p = 0.953). Administration of 400 μg/mL PPE insignificantly decreased cyclin D1 expression (p = 0.149). The concentration of PPE at 50, 100, and 200 μg/mL induced cell apoptosis of HT-29 cells initially, but the level of apoptosis subsequently decreased (p = 0.416). Furthermore, the expressions of p53 and Bcl-xL decreased following treatment with PPE at 50, 100 and 200 μg/mL but increased for the PPE 400 μg/mL group (p = 0.000). Conclusion : PPE reduced the expressions of p53, Ki67, cyclin D1, and Bcl-xL insignificantly as it it generally failed inhibit cell proliferation and promote cell apoptosis of HT-29 cells. Keywords : Bcl-xL, Colon cancer, Cyclin D1, Human colon adenocarcinoma cell line HT-29, Proliferation marker Ki67, Tumor protein p53

The Difference of STAT3 Binding Pattern on -5434C and -5434T REN and Its Consequence on Serum Renin Levels

Imama Maslahah 1, Mohammad Saifur Rohman 2, Widodo 3, Agustina Tri Endharti 4, Didik Huswo 5. 1 Biomedical Sciences, Faculty of Medicine, University of Brawijaya, Malang, Indonesia, 2 Department of Cardiology and Vascular Medicine, Faculty of Medicine, Brawijaya University-Saiful Anwar General Hospital, Malang, Indonesia, 3 Biology Department, Faculty of Mathematics and Sciences, University of Brawijaya, Malang, Indonesia, 4 Parasitology Department, Faculty of Medicine, University of Brawijaya, Malang, Indonesia, 5 Biology Department, Faculty of Mathematics and Sciences, University of Brawijaya, Malang, Indonesia

Pioglitazone Increase PPAR-γ Expression, Decrease MMP-9, MMP-13, VEGF, NO and TNF-α Secretion in IL-1β-induced Chondrocyte

Osteoarthritis is the chronic musculoskeletal disorders. It is characterized by destruction of articular cartilage, proinflamatory mediator secretion and breakdown of cartilage matrix.MMP-9 and MMP-13 are biomarkers in matrix degradation in osteoarthritis. MMP-9 can activate pro MMP-13 and stimulates MMP-13 secretion, MMP-13 also can activate MMPs. NO (nitric oxide) is the essential production of catabolic factor in chondrocyte, its caused by the cytokineproinflamatory responses. VEGF is the essential component for ossification and osteophyte formation.Recent studies suggest that activation of PPAR-γ with pioglitazone (agonist PPAR-γ) is an interesting target for the disease. PPAR-γ is a transcription factor that is also expressed in chondrocytes. The aim of this study to determine the effects of pioglitazone on MMP-9, MMP-13, NO, VEGF, TNF-αsecretion andPPAR-γ expressionby chondrocytes.The sample of this research is chondrocyte cell line induced by IL-1β then exposed with pioglitazone. MMP-9, MMP-13,VEGF and TNF-α were measured using ELISA, NOwas measured using colorimetry assay, PPAR-γ expression was measured by real time PCR. Pioglitazone exposure increased PPARγ expression significantly, and in contrast they are also decreaseMMP-9, MMP-13, NO, VEGF and TNF-αsecretion in all groups. This results show that pioglitazone have a role for treatmentin osteoarthritis by decreasing catabolic and inflamatory responses of chondrocyte.