Metallothionein-3 (MT-3) in the Human Adrenal Cortex and its Disorders

Felizola, Saulo J.A.; Nakamura, Yasuhiro; Arata, Yuki; Ise, Kazue; Satoh, Fumitoshi; Rainey, William E.; Midorikawa, Sanae; Suzuki, Shinichi; Sasano, Hironobu

doi:10.1007/s12022-013-9280-9

Cited by 26 publications

(9 citation statements)

References 36 publications

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“…Noteworthy, we found that normal adrenal cortex-derived cells express mRNA encoding hMT-3, which is in good agreement with study by Felizola et al . [ 20 ]. However, the 2 -ΔΔ Ct values were considerably lower (0.699–2.365) compared with HR Nbl specimens.…”

Section: Resultsmentioning

confidence: 99%

Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin

et al. 2017

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Human metallothionein-3 (hMT-3), also known as growth inhibitory factor, is predominantly expressed in the central nervous system. hMT-3 is presumed to participate in the processes of heavy metal detoxification, regulation of metabolism and protection against oxidative damage of free radicals in the central nervous system; thus, it could play important neuromodulatory and neuroprotective roles. However, the primary functions of hMT-3 and the mechanism underlying its multiple functions in neuroblastoma have not been elucidated so far. First, we confirmed relatively high expression of hMT-3 encoding mRNA in biopsies (n = 23) from high-risk neuroblastoma subjects. Therefore, we focused on investigation of the impact of hMT-3 up-regulation in N-Myc amplifying neuroblastoma cells. The differentially up-regulated genes involved in biological pathways related to cellular senescence and cell cycle were identified using electrochemical microarray with consequent bioinformatic processing. Further, as experimental verification of microarray data, the cytotoxicity of the cisplatin (CDDP) was examined in hMT-3 and mock cells by MTT and clonogenic assays. Overall, our data strongly suggest that up-regulation of hMT-3 positively correlates with the genes involved in oncogene-induced senescence (CDKN2B and ANAPC5) or apoptosis (CASP4). Moreover, we identified a significant increase in chemoresistance to cisplatin (CDDP) due to hMT-3 up-regulation (24IC50: 7.5 vs. 19.8 μg/ml), indicating its multipurpose biological significance.

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Section: Resultsmentioning

confidence: 99%

Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin

et al. 2017

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“…Thiol group level depends on the content of protective plant peptides such as phytochelatins, metallothioneins, and glutathione. They are involved in the detoxification of heavy metals and are required for functioning of the antioxidant system ( Ha et al 1999 ; Pompella et al 2003 ; Felizola et al 2014 ). Total protein content depends on the synthesis of protective proteins such as antioxidant enzymes and stress and signaling proteins ( Srivastava et al 2005 ).…”

Section: Discussionmentioning

confidence: 99%

Hormesis and Paradoxical Effects of Drooping Birch (Betula pendula Roth) Parameters Under Motor Traffic Pollution

Erofeeva

2015

Dose-Response

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Various plant indexes are used or recommended for bioindication. However, the nonmonotonic dose–response dependences (hormesis and paradoxical effects) of these indexes are insufficiently explored upon exposure to pollution. We studied the dependences of these Betula pendula indexes on the intensity of motor traffic pollution. Regression analysis did not reveal any dependence of chlorophyll and carotenoid content on traffic intensity (in 2008 and 2010-2013). Lipid peroxidation rate had different versions of paradoxical effects in 2008 and 2010 to 2012 and increased in comparison with control under an increase in pollution level in 2013. In 2010 to 2012, all dose–response dependences for total protein and thiol group content were biphasic and multiphasic paradoxical effects. In 2013, an increase in traffic intensity induced a linear reduction in protein content and an increase in thiol group level in comparison with the control. In most cases, the studied phenological indexes and seed production decreased monotonically in comparison with the control following an increase in traffic intensity. Only in 2010 and 2013, share of fallen leaves had hormesis and paradoxical effect accordingly. Fluctuating asymmetry had a paradoxical effect and hormesis in 2008 and 2012, accordingly, and increased in comparison with the control under an increase in the level of pollution in 2010 to 2011.

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“…RNA isolation with subsequent cDNA production and qPCR technique were performed as previously reported (Felizola et al 2013b, Felizola et al 2014). The primer sequences used in our study were: PCP4 forward 5′-TGA CAT GGA TGC ACC AG-′3, reverse 5′-GTG TGG ATT GTG TGT GG-′3; CYP11B1 forward 5′-CCC AGC ACA AAT GGA ACT CCC GA-′3, reverse 5′-CCG CTT AAT GAC TCT GAC AGT CTG CG-′3; CYP11B2 forward 5′-TCC AGG TGT GTT CAG TAG TTC C-′3, reverse 5′-GAA GCC ATC TCT GAG GTC TGT G-′3; RPL13A forward 5′-CCT GGA GGA GAA GAG GAA AG-′3, reverse 5′-TTG AGG ACC TCT GTG TAT TT-′3.…”

Section: Methodsmentioning

confidence: 99%

PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

Felizola¹,

Nakamura²,

Ono³

et al. 2014

Journal of Molecular Endocrinology

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Purkinje cell protein 4 (PCP4) is a calmodulin (CaM) binding protein that accelerates calcium association and dissociation with CaM. It has been previously detected in aldosterone-producing adenomas (APA) but details on its expression and function in adrenocortical tissues have remained unknown. Therefore, we performed the immunohistochemical analysis of PCP4 in the following tissues: normal adrenal (NA; n=15), APA (n=15), cortisol producing adenomas (CPA; n=15) and idiopathic hyperaldosteronism cases (IHA; n=5). APA samples (n=45) were also submitted to quantitative RT-PCR (qPCR) of PCP4, CYP11B1, and CYP11B2, as well as DNA sequencing for KCNJ5 mutations. Transient transfection analysis using PCP4 siRNA was also performed in H295R adrenocortical carcinoma cells, following ELISA analysis, and CYP11B2 luciferase assays were also performed after PCP4 vector transfection in order to study the regulation of PCP4 protein expression. In our findings, PCP4 immunoreactivity was predominantly detected in APA and in the zona glomerulosa (ZG) of NA and IHA. In APA, the mRNA levels of PCP4 were significantly correlated with those of CYP11B2 (P<0.0001) and were significantly higher in cases with KCNJ5 mutation than wild-type (P=0.005). Following PCP4 vector transfection, CYP11B2 luciferase reporter activity was significantly higher than controls in the presence of angiotensin-II. Knockdown of PCP4 resulted in a significant decrease in CYP11B2 mRNA levels (P=0.012) and aldosterone production (P=0.011). Our results indicate that PCP4 is a regulator of aldosterone production in normal, hyperplastic and neoplastic human adrenocortical cells.

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Metallothionein-3 (MT-3) in the Human Adrenal Cortex and its Disorders

Cited by 26 publications

References 36 publications

Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin

Comparative gene expression profiling of human metallothionein-3 up-regulation in neuroblastoma cells and its impact on susceptibility to cisplatin

Hormesis and Paradoxical Effects of Drooping Birch (Betula pendula Roth) Parameters Under Motor Traffic Pollution

PCP4: a regulator of aldosterone synthesis in human adrenocortical tissues

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