Ontogeny, aging, and gender-related changes in hepatic multidrug resistant protein genes in rats

Zhu, Qiong-Ni; Hou, Wei-Yu; Xu, Shang‐Fu; Lu, Yuan‐Fu; Liu, Jie

doi:10.1016/j.lfs.2016.11.022

Cited by 18 publications

(11 citation statements)

References 45 publications

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“…We have examined the constitutive expression of agerelated drug processing genes changes, from prenatal (−2 d), neonatal (1, 7, 14 and 21 d), at puberty (28 and 35 d), at adulthood (60 and 180 d), and at aging (540 and 800 d), and characterized the age-related expression of kidney transporters [14], hepatic uptake Oatp transporters [15], hepatic efflux transporters [16], and hepatic Nrf2 antioxidant pathways [17]. The goals of this study were to quantify the mRNA abundance of 10 major GST isoforms in rat livers, to detect agerelated mRNA and/or protein changes of these isoforms, and to characterize clear age-related patterns from these data.…”

Section: Introductionmentioning

confidence: 99%

Age-associated changes in GSH S-transferase gene/proteins in livers of rats

Hou

Liu

et al. 2018

Redox Report

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Objectives: Glutathione S-transferases (GSTs) are phase-II metabolic enzymes playing important roles in drug metabolism, anti-oxidative stress and anti-aging. Age is a key factor influencing GSTs expression. Thus, age-related changes of 10 GSTs were examined. Methods: Livers from male Sprague-Dawley rats at fetus (−2 d), neonates (1, 7, 14 and 21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d), were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 d were also extracted for selected protein analysis by Western-blot. Results: The expression of GSTA1 and GSTP1 increased over the life span and the expression of GSTA4, GSTO1 and GSTZ1 gradually increased until adulthood, and slightly decreased at 800 days. The expression of GSTM1, GSTM3, GSTT1, GSTT2 and GSTK1 gradually increased until adulthood, but significantly decreased during aging of 540 and 800 days. There is a small peak at 7-14 d for GSTA1, GSTP1 and GSTZ1. The protein expression of GSTA1, GSTM1 and GSTP1 followed the trend of mRNA changes. Discussion: This study characterized three expression patterns of 10 GSTs during development and aging in rat liver, adding to our understanding of anti-aging role of GSTs.

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Section: Introductionmentioning

confidence: 99%

Age-associated changes in GSH S-transferase gene/proteins in livers of rats

Hou

Liu

et al. 2018

Redox Report

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“…There are three unique features of the current study: (1) Most of the studies on agerelated changes in hepatic CYPs are performed in mice, (Cui et al 2012;Hart et al 2009;Li et al 2009) this study characterized CYPs and NRs in rats, another commonly-used laboratory animals; (2) Most of the age-related changes in hepatic P450 are focused on the developmental stages to maturation, (Asaoka et al 2010;Bondarenko et al 2016;Cui et al 2012;de Zwart et al 2008;Kilanowicz et al 2015;Park et al 2016) and this study covered the whole life span, and (3) this study extended our efforts to characterize age-and sex-related changes in hepatic drug transporters Zhu et al 2017) and defense mechanisms. Xu et al 2018a;Xu et al 2018b) P450-1 family CYP1 family is responsible for activation of toxicants and drugs.…”

Section: Discussionmentioning

confidence: 94%

“…(Hines 2013;Saghir et al 2012) We have collected liver samples of Sprague Dawley (SD) rats from prenatal (-2 d), neonatal (1, 7, and 14 d), weanling (21 d and hepatic efflux MRP transporters. (Zhu et al 2017) We have also used these samples to characterize the Nrf2 antioxidant pathways, (Xu et al 2018b) glutathione S-transferases, (Xu et al 2018a) and the antioxidant metallothionein gene expression. The goals of the current study were to use these samples to quantify the expression of 16 major CYP isoforms in rat livers, 5 corresponding nuclear receptors (NRs), and 4 phase-II conjugation genes.…”

Section: Introductionmentioning

confidence: 99%

Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats

Xie

et al. 2019

Preprint

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Cytochrome P450s (CYPs) are phase-I metabolic enzymes playing important roles in drug metabolism, dietary chemicals and endogenous molecules. Age is a key factor influencing P450s expression. Thus, age-related changes of CYP 1-4 families and bile acid homeostasis-related CYPs, the corresponding nuclear receptors and a few phase-II genes were examined. Livers from male Sprague-Dawley rats at fetus (-2 d), neonates (1, 7, and 14 d), weanling (21 d), puberty (28 and 35 d), adulthood (60 and 180 d), and aging (540 and 800 d) were collected and subjected to qPCR analysis. Liver proteins from 14, 28, 60, 180, 540 and 800 days of age were also extracted for selected protein analysis by Western-blot. In general, there were three patterns of their expression: Some of the drug-metabolizing enzymes and related nuclear receptors were low in fetal and neonatal stage, increased with liver maturation and decreased quickly at aging (AhR, Cyp1a1, Cyp2b1, Cyp2b2, Cyp3a1, Cyp3a2, Ugt1a2); the majority of P450s (Cyp1a2, Cyp2c6, Cyp2c11, Cyp2d2, Cyp2e1, CAR, PXR, FXR, Cyp7a1, Cyp7b1. Cyp8b1, Cyp27a1, Ugt1a1, Sult1a1, Sult1a2) maintained relatively high levels throughout the adulthood, and decreased at 800 days of age; and some had an early peak between 7 and 14 days (CAR, PXR, PPARα, Cyp4a1, Ugt1a2). The protein expression of CYP1A2, CYP2B1, CYP2E1, CYP3A1, CYP4A1, and CYP7A1 corresponded the trend of mRNA changes. In summary, this study characterized three expression patterns of 16 CYPs, 5 nuclear receptors, and 4 phase-II genes during development and aging in rat liver, adding to our understanding of age-related CYP expression changes and age-related disorders.

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“…(Hines 2013;Saghir et al 2012) Considering the variations of P450 in children, adult, and elderly, this study was initiated to characterize age-associated changes in hepatic P450, to extend our prior work on age-associated changes in hepatic uptake Oatp transporters , efflux MRP transporters. (Zhu et al 2017), the Nrf2 antioxidant pathways, (Xu et al 2018b), glutathione S-transferases, (Xu et al 2018a) and the antioxidant metallothionein gene expression. (Hou WY 2014) The expression of 16 major CYP isoforms, 5 corresponding nuclear receptors (NRs), and 4 phase-II conjugation genes were examined.…”

Section: Manuscript To Be Reviewedmentioning

confidence: 99%

“…PeerJ reviewing PDF | (2019:04:36465:1:0:NEW 13 Jun 2019)Manuscript to be reviewed characterize age-and sex-related changes in hepatic drug transportersZhu et al 2017) and defense mechanisms Xu et al 2018a;. Xu et al responsible for activation of toxicants and drugs.…”

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Peer Review #1 of "Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats (v0.2)"

2019

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Ontogeny, aging, and gender-related changes in hepatic multidrug resistant protein genes in rats

Cited by 18 publications

References 45 publications

Age-associated changes in GSH S-transferase gene/proteins in livers of rats

Age-associated changes in GSH S-transferase gene/proteins in livers of rats

Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats

Peer Review #1 of "Age-associated changes of cytochrome P450 and related phase-2 gene/proteins in livers of rats (v0.2)"

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