A5044573618- Hormonal Regulation and Hypertension
- Estrogen and related hormone effects
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Sexual Differentiation and Disorders
- Pharmacogenetics and Drug Metabolism
- Ubiquitin and proteasome pathways
- Endoplasmic Reticulum Stress and Disease
- DNA Repair Mechanisms
- Cancer, Stress, Anesthesia, and Immune Response
- Reproductive biology and impacts on aquatic species
- Hormonal and reproductive studies
- Heat shock proteins research
- Metabolism and Genetic Disorders
- RNA Research and Splicing
- Protein Degradation and Inhibitors
- Steroid Chemistry and Biochemistry
- Redox biology and oxidative stress
- Sulfur Compounds in Biology
- Retinoids in leukemia and cellular processes
- Nuclear Structure and Function
- Cancer-related Molecular Pathways
- Genomics and Chromatin Dynamics
- PI3K/AKT/mTOR signaling in cancer
- S100 Proteins and Annexins
- Pediatric Pain Management Techniques
National Taiwan University
2014-2024
Czech Academy of Sciences, Institute of Physiology
2017
Institute of Molecular Biology, Academia Sinica
1990-2014
China Pharmaceutical University
2013
Academia Sinica
2001
National Defense Medical Center
1997-1999
University of Illinois Urbana-Champaign
1990
BACKGROUND: Previous studies have shown that local anesthetics may induce apoptosis in some cell types. In this study, we investigated the apoptotic effects of human breast tumor cells. METHODS: Human cancer (MCF-7) and mammary epithelial (MCF-10A) lines were treated with lidocaine and/or bupivacaine. Cell viability, DNA fragmentation, annexin V immunofluorescence staining assessed. The on apoptosis-related protein expression by Western blot analysis. findings extended to an vivo xenograft...
Local anesthetics are frequently used in fine-needle aspiration of thyroid lesions and locoregional control persistent or recurrent cancer. Recent evidence suggests that local have a broad spectrum effects including inhibition cell proliferation induction apoptosis neuronal other types cells. In this study, we demonstrated treatment with lidocaine bupivacaine resulted decreased viability colony formation both 8505C K1 cells dose-dependent manner. Lidocaine induced apoptosis, necrosis high...
Congenital adrenal hyperplasia (CAH) is a common recessive genetic disease caused mainly by steroid 21-hydroxylase (P450c21) deficiency. Many forms of CAH exist resulting from various mutations the CYP21B gene. We sequenced cDNA normal person and its genes patient with simple virilizing CAH. When comparing several sequences, we found it was polymorphic. In patient, single base substitution replaced Ile172 (ATC) Asn (AAC) in one allele while Arg356 (CGG) converted to Trp (TGG) other. A...
Steroid deficiencies are diseases affecting salt levels, sugar and sexual differentiation. To study steroid deficiency in more detail, we used a gene-targeting technique to insert neo gene into the first exon disrupt Cyp11a1, biosynthetic pathways. Cyp11a1 null mice do not synthesize steroids. They die shortly after birth, but can be rescued by injection. Due lack of feedback inhibition glucocorticoid, their circulating ACTH levels exceedingly high; this results ectopic Cyp21 expression...
The CYP11A1 gene encodes P450scc (cholesterol side-chain cleavage enzyme), which catalyzes the first step for synthesis of steroids. Expression is controlled by transcription factor SF-1 (steroidogenic 1). Two functional SF-1-binding sites, P and U, located at −40 −1,600 regions gene, have been identified, but their exact functions with respect to basal activation vs. cAMP response not dissected. We addressed this question examining ability mutated human promoter drive LacZ reporter...
Abstract Voltage-gated CLC-1 chloride channels play a critical role in controlling the membrane excitability of skeletal muscles. Mutations human have been linked to hereditary muscle disorder myotonia congenita. We previously demonstrated that disease-associated A531V mutant protein may fail pass endoplasmic reticulum quality control system and display enhanced degradation as well defective trafficking. Currently molecular basis for is virtually unknown. Here we aim identify E3 ubiquitin...
The insulin family of growth factors (insulin, IGF1, and IGF2) are critical in sex determination, adrenal differentiation, testicular function. Notably, the IGF system has been reported to mediate proliferation steroidogenic cells. However, precise role contribution membrane receptors mediating those effects, namely, insülin receptor (INSR) type-I insülin-like factor (IGF1R), have not, oür knowledge, investigated. We show here that specific deletion both Insr Igf1r cells mice leads severe...
The first step in the synthesis of steroids is catalysed by cytochrome P-450ssc (cholesterol-side-chain cleavage enzyme). We have investigated this enzyme three cultured cell lines at protein and hormone secretion levels. Hormone levels were measured an immunoassay using a monoclonal antibody against progesterone. level was detected polyclonal antibodies directed P-450scc fusion overproduced Escherichia coli. Utilizing bacteriophage T7 promoter expression system, large amount human produced...
Liver receptor homolog‐1 (LRH‐1; NR5A2) is an orphan member of the nuclear superfamily, mainly expressed in endoderm‐derived tissues and ovary. In ovarian granulosa luteal cells, LRH‐1 regulates expression genes associated with steroidogenesis. can be transported to transcriptionally inactive bodies after conjugation small ubiquitin‐related modifier (SUMO). present study, we investigated effects SUMO modification at five lysine residues rat cells. Lysine 289 could conjugated SUMO‐1 vitro ,...
We report here the study of human CYP11A1 promoter in driving tissue-specific, developmentally and hormonally regulated reporter gene expression. A 4.4-kb fragment containing all known regulatory elements is more efficient than a short basal fused to an upstream adrenal enhancer LacZ expression both cell culture transgenic mice. The controlled by 4.4- 2.3-kb promoters was expressed cortex, testicular Leydig cells, ovarian corpora lutea, granulosa cells. Transgene adrenals stimulated ACTH,...
Cytochrome P450c21 (steroid 21-hydroxylase) is a key enzyme in the synthesis of cortisol, whose deficiency cause common genetic disease, congenital adrenal hyperplasia. We have expressed E. coli and mammalian cells. In coli, cDNA was cloned into T7 expression vector to produce large amount fusion protein, which enabled antiserum production. cells, plasmid containing full-length (phc21) constructed transfected COS-1 cells active P450c21, detected by immunoblotting 21-hydroxylase activity...
The stress-responding protein, GADD45α, plays important roles in cell cycle checkpoint, DNA repair and apoptosis. In our recent study, we demonstrate that GADD45α undergoes a dynamic ubiquitination degradation vivo, which process can be blocked by the cytotoxic reagent, arsenite, resulting accumulation to activate JNKs death pathway, thereby revealing novel mechanism for cellular functional regulation. But factors involved stability modulations are unidentified. Here, demonstrated MDM2 was...
Voltage-gated ClC-2 channels are essential for chloride homeostasis. Complete knockout of mouse leads to testicular degeneration and neuronal myelin vacuolation. Gain-of-function loss-of-function mutations in the ClC-2-encoding human CLCN2 gene linked genetic diseases aldosteronism leukodystrophy, respectively. The protein homeostasis (proteostasis) mechanism is currently unclear. Here, we aimed identify molecular endoplasmic reticulum-associated degradation ClC-2, explore pathophysiological...
The effective treatment of breast cancer remains a profound clinical challenge, especially due to drug resistance and metastasis which unfortunately arise in many patients. transcription inhibitor 5,6-dichloro-1-beta-D-ribofuranosyl-benzimidazole (DRB), as selective cyclin-dependent kinase 9, was shown be inducing apoptosis various hematopoietic malignancies. However, the anticancer efficacy DRB against is still unclear. Herein, we demonstrated that administration cell line led inhibition...
The most common cause of congenital adrenal hyperplasia is deficiency cytochrome P450c21 (21-hydroxylase), which catalyzes the synthesis steroids. We have cloned human cDNA into yeast expression vectors under control either glyceraldehyde-3-phosphate-dehydrogenase (GAPDH) promoter or aldehyde-dehydrogenase (ADH) promoter. RNA, protein, and enzyme activity can be detected, indicating that both promoters drive P450c21. expressed conversion its substrates, with Km Vmax values 0.33 microM 280...