Papers by Asma Chinigarzadeh
Abstract: Genistein has been reported to stimulate luminal HCO3 − secretion. We hypothesized that... more Abstract: Genistein has been reported to stimulate luminal HCO3 − secretion. We hypothesized that genistein mediates this effect via SLC26A6 and SLC4A4 (NBCe1) transporters. Our study aimed to: investigate changes in uterine fluid pH, Na+ and HCO3− concentration and expression of uterine SLC26A6 and NBCe1 under genistein effect. Ovariectomized adult female rats received 25, 50 and 100 mg/kg/day genistein for a week with and without ICI 182780. A day after the last injection, in vivo uterine perfusion was performed to collect uterine fluid for Na+, HCO3 − and pH determination. The animals were then sacrificed and uteri were removed for mRNA and protein expression analyses. SLC26A6 and NBCe1-A and NBCe1-B distribution were visualized by immunohistochemistry (IHC). Genistein at 50 and 100 mg/kg/day stimulates uterine fluid pH, Na+ and HCO3− concentration increase. Genistein at 100 mg/kg/day up-regulates the expression of SLC26A6 and SLC4A4 mRNA, which were reduced following concomitant...
— Malaria is a major public health problem caused by Plasmodium falciparum, a parasite that infec... more — Malaria is a major public health problem caused by Plasmodium falciparum, a parasite that infects red blood cells. Recently, several polyphenolic compounds have been reported capable of preventing the progression of malaria parasite. This observation may be related to NAD (P) H: quinon oxidoreductase: a flavoprotein responsible for catalyzing two-electron reduction and detoxification of quinones and their derivatives. In this study the 2123 bp of the 5 ` upstream of the first transcription start site was successfully isolated. Based on the bioinformatic program, several regulatory regions such as Antioxidant Response Element (ARE) may be responsible for the direct regulation of polyphenols on this enzyme. It was predicted at-477 from the first transcription start site. Upon isolation, this fragment was used in a cloning process into the pGL3 Basic vector and transformed to E.coli DH5α competent cells.
Worldwide mortality and morbidity from infectious diseases is being replaced by non infectious ch... more Worldwide mortality and morbidity from infectious diseases is being replaced by non infectious chronic diseases, such as cancer, obesity, type II diabetes, cardiovascular diseases, neurodegenerative diseases and aging which may involve inflammation. Vascular endothelial growth factor (VEGF) as a potent pro-inflammatory cytokine is elevated in many human diseases, or animal models of human disease, which are mentioned above. Compounds derived from botanic sources, such as polyphenolic compounds express anti-inflammatory activity by modulation of pro-inflammatory gene expression. We hypothesized this effect may related to control regulation of VEGF gene promoter. In this study, the VEGF promoter was isolated using nested PCR to define the transcription factors binding sites. The human VEGF promoter region was cloned in DH5 alpha Ecoli for future investigation.
Malaria is a major public health problem caused by Plasmodium falciparum, a parasite that infects... more Malaria is a major public health problem caused by Plasmodium falciparum, a parasite that infects red blood cells. Recently, several polyphenolic compounds have been reported capable of preventing the progression of malaria parasite. This observation may be related to NAD (P) H: quinon oxidoreductase: a flavoprotein responsible for catalyzing two-electron reduction and detoxification of quinones and their derivatives. In this study the 2123 bp of the 5` upstream of the first transcription start site was successfully isolated. Based on the bioinformatic program, several regulatory regions such as Antioxidant Response Element (ARE) may be responsible for the direct regulation of polyphenols on this enzyme. It was predicted at -477 from the first transcription start site. Upon isolation, this fragment was used in a cloning process into the pGL3 Basic vector and transformed to E.coli DH5? competent cells
Journal of Biochemical and Molecular Toxicology, 2016
We hypothesized that genistein could affect the chloride (Cl(-) ) and bicarbonate (HCO3(-) ) secr... more We hypothesized that genistein could affect the chloride (Cl(-) ) and bicarbonate (HCO3(-) ) secretory mechanisms in uterus. Ovariectomized female rats were given estradiol or estradiol plus progesterone with 25, 50, or 100 mg/kg/day genistein. Following completion of the treatment, uterine fluid Cl(-) and HCO3(-) concentrations were determined by in vivo uterine perfusion. Uteri were subjected for molecular biological analysis (Western blot, qPCR, and immunohistochemistry) to detect levels of expression of Cystic Fibrosis transmembrane regulator (CFTR), Cl(-) /HCO3(-) exchanger (SLC26a6), Na(+) /HCO3(-) cotransporter (SLC4a4), and estrogen receptor (ER)-α and β. Coadministration of genistein resulted in decrease in Cl(-) and HCO3(-) concentrations and expression of CFTR, SLC26a6, SLC4a4, and ER-α and ER-β in the uteri of estradiol-treated rats. In estradiol plus progesterone-treated rats, a significant increase in the above parameters were observed following high-dose genistein treatment except for the SLC24a4 level. In conclusion, genistein-induced changes in the uterus could affect the reproductive processes that might result in infertility.
Steroids, 2016
In this study, effects of estradiol, progesterone and genistein on uterine aquaporin (AQP)-1, 2, ... more In this study, effects of estradiol, progesterone and genistein on uterine aquaporin (AQP)-1, 2, 5 and 7 expression were investigated in sex-steroid deficient state which could help to elucidate the mechanisms underlying uterine fluid volume changes that were reported under these hormone and hormone-like compound influences. Uteri from ovariectomized, female Sprague-Dawley rats receiving seven days estradiol, progesterone or genistein (25, 50 and 100mg/kg/day) were harvested and levels of AQP-1, 2, 5 and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR (qPCR) respectively. Distribution of these proteins in uterus was observed by immunohistochemistry. Genistein caused a dose-dependent increase in uterine AQP-1, 2, 5 and 7 protein and mRNA expression, however at the levels lower than following estradiol or progesterone stimulations. Effects of genistein were antagonized by estradiol receptor blocker, ICI 182780. Estradiol caused the highest AQP-2 protein and mRNA expression while progesterone caused the highest AQP-1, 5 and 7 protein and mRNA expression in uterus. AQP-1, 2, 5 and 7 protein were found to be distributed in the myometrium as well as in uterine luminal and glandular epithelia and endometrial blood vessels. In conclusion, the observed effects of estradiol, progesterone and genistein on uterine AQP-1, 2, 5 and 7 expression could help to explain the differences in the amount of fluid accumulated in the uterus under these different conditions.
Worldwide mortality and morbidity from infectious diseases is being replaced by non infectious ch... more Worldwide mortality and morbidity from infectious diseases is being replaced by non infectious chronic diseases, such as cancer, obesity, type II diabetes, cardiovascular diseases, neurodegenerative diseases and aging which may involve inflammation. Vascular endothelial growth factor (VEGF) as a potent pro-inflammatory cytokine is elevated in many human diseases, or animal models of human disease, which are mentioned above. Compounds derived from botanic sources, such as polyphenolic compounds express anti-inflammatory activity by modulation of pro-inflammatory gene expression. We hypothesized this effect may related to control regulation of VEGF gene promoter. In this study, the VEGF promoter was isolated using nested PCR to define the transcription factors binding sites. The human VEGF promoter region was cloned in DH5 alpha Ecoli for future investigation.
Malaria is a major public health problem caused by Plasmodium falciparum, a parasite that infects... more Malaria is a major public health problem caused by Plasmodium falciparum, a parasite that infects red blood cells. Recently, several polyphenolic compounds have been reported capable of preventing the progression of malaria parasite. This observation may be related to NAD (P) H: quinon oxidoreductase: a flavoprotein responsible for catalyzing two-electron reduction and detoxification of quinones and their derivatives. In this study the 2123 bp of the upstream of the first transcription start site was successfully isolated. Based on the bioinformatic program, several regulatory regions such as Antioxidant Response Element (ARE) may be responsible for the direct regulation of polyphenols on this enzyme. It was predicted at -477 from the first transcription start site. Upon isolation, this fragment was used in a cloning process into the pGL3 Basic vector and transformed to E.coli DH5α competent cells.
Environmental Toxicology and Pharmacology, 2015
Maintaining near normal uterine fluid pH is important for restoring uterine function after menopa... more Maintaining near normal uterine fluid pH is important for restoring uterine function after menopause. We hypothesized that genistein could restore uterine fluid pH via its effect on NHE expression. This study therefore investigated changes in uterine NHE-1, 2 and 4 expression under genistein influence. Ovariectomized female rats received genistein (25, 50 or 100mg/kg/day) for seven consecutive days. Uteri were harvested and NHE-1, 2 and 4 mRNA expression were analyzed by Real-time PCR while distribution of these transporters' protein was observed by immunohistochemistry. Expression of NHE-1, 2 and 4 mRNA increased with increasing doses of genistein which was antagonized by ICI 182780. Under genistein influence, NHE-1, 2 and 4 proteins were found to be distributed at apical membrane of endometrial luminal epithelia. Enhanced expression of NHE-1, 2 and 4 in ovariectomised rat uteri by genistein might help to restore pH of uterine fluid which could be useful for women after menopause.
Theriogenology, 2015
Estrogen, progesterone, and genistein could induce changes in uterine fluid volume and Na(+) conc... more Estrogen, progesterone, and genistein could induce changes in uterine fluid volume and Na(+) concentration. Progesterone upregulates expression of epithelial sodium channel (ENaC) and Na(+)/K(+)-ATPase which contributed toward these changes. However, effects of estrogen and genistein were unknown. This study therefore investigated changes in expression of these proteins in the uterus under estrogen, progesterone, and genistein influences to further understand mechanisms underlying sex steroids and phytoestrogen effects on uterine fluid Na(+) regulation. In this study, uteri of ovariectomized female rats receiving 7-day treatment with genistein (25, 50, and 100 mg/kg/day), estrogen (0.8 × 10(-4) mg/kg/day), or progesterone (4 mg/kg/day) were harvested, and expression levels of α-, β-, and γ-ENaC proteins and messenger RNAs (mRNAs) and α-Na(+)/K(+)-ATPase protein were determined by Western blotting (proteins) and real-time polymerase chain reaction (mRNA). Meanwhile, distribution of α-, β-, and γ-ENaC and α-Na(+)/K(+)-ATPase proteins in the uterus was identified by immunohistochemistry. Our findings indicated that expression of α-, β-, and γ-ENaC proteins and mRNAs and α-Na(+)/K(+)-ATPase protein were enhanced under progesterone influence. Lower expressions were noted under estrogen and genistein influences compared to progesterone. Under estrogen, progesterone, and genistein influences, α- and β-ENaC were distributed at apical membrane and γ-ENaC was distributed at apical and basolateral membranes of uterine luminal epithelia. Under progesterone influence, α-Na(+)/K(+)-ATPase was highly expressed at basolateral membrane. In conclusion, high expression of α-, β-, and γ-ENaC and α-Na(+)/K(+)-ATPase under progesterone influence would contribute toward increased uterine fluid Na(+) reabsorption, whereas lesser expression of these proteins under estrogen and genistein influences would contribute toward lower reabsorption of uterine fluid Na(+).
International Journal of Molecular Sciences, 2014
Environmental Toxicology, 2016
We hypothesized that genistein can interfere with the regulation of uterine fluid volume, secreti... more We hypothesized that genistein can interfere with the regulation of uterine fluid volume, secretion rate and expression of aquaporin in the uterus by female sex-steroids, i.e., estrogen and progesterone. Therefore, the aims of this study were to investigate changes in these parameters in the presence of genistein and female sex-steroids. Female Sprague-Dawley rats were ovariectomized and received 3-days estradiol-17β benzoate (E2) plus genistein (25, 50, or 100 mg kg(-1) day(-1) ) or 3-days E2 followed by 3-days E2 plus progesterone with genistein (25, 50, or 100 mg kg(-1) day(-1) ). A day after last treatment, uterine fluid secretion rate was determined by in vivo uterine perfusion with rats under anesthesia. Animals were sacrificed and uteri were harvested and subjected for histological analyses. Luminal/outer uterine circumference was determined and distribution of AQP-1, 2, 5, and 7 in endometrium was visualized by immunofluorescence. Expression of AQP-1, 2, 5, and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR respectively. Combined treatment of E2 with high dose genistein (50 and 100 mg kg(-1) day(-1) ) resulted in significant decrease in uterine fluid volume, secretion rate and expression of AQP-1, 2, 5, and 7 proteins and mRNAs in uterus (p < 0.05). No significant changes in these parameters were observed when 25 mg kg(-1) day(-1) genistein was given with E2 or when genistein was given with E2 followed by E2 plus progesterone Conclusions: Decreased in uterine fluid volume, secretion rate and AQP-1, 2, 5, and 7 expression in the uterus by high dose genistein in the presence of E2 could potentially affect female fertility. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 832-844, 2017.
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Papers by Asma Chinigarzadeh