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教育实践与研究 2025年第1期 51-55页

作者：贾艳洁黄梅玲厦门市翔安区马巷中心小学福建厦门361100 厦门市翔安区教师进修学校福建厦门361100

对厦门市小学科学教师pepck现状进行测查,从分析测查结果发现,本市小学科学教师的pepck结构不均衡;小学科学教师对自身教师理解的过程性评价知识认知不准确;小学科学教师缺少设计评价和选择、使用评价方法的策略知识;小学科学教师的PEPC... 详细信息

对厦门市小学科学教师pepck现状进行测查,从分析测查结果发现,本市小学科学教师的pepck结构不均衡;小学科学教师对自身教师理解的过程性评价知识认知不准确;小学科学教师缺少设计评价和选择、使用评价方法的策略知识;小学科学教师的pepck的整体得分偏高。建议教师转变传统评价观念,增强过程性评价意识;教师积极开展过程性评价知识学习,形成深入的系统的过程性评价知识体系;教师基于课堂落实过程性评价策略,提高过程性评价的实践经验;为教师们构建过程性教学评价合作平台,分享过程性教学评价经验;从而促进小学科学教师pepck素养的提升。

关键词：小学科学过程性评价 pepck 现状测评提升建议

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pepck-C reexpression in the liver counters neonatal hypoglycemia in Pck1^del/del mice, unmasking role in non-gluconeogenic tissues

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JOURNAL OF PHYSIOLOGY AND BIOCHEMISTRY 2017年第1期73卷 89-98页

作者： Semakova, Jana Hyrossova, Petra Mendez-Lucas, Andres Cutz, Ernest Bermudez, Jordi Burgess, Shawn Alcantara, Soledad Perales, Jose C. Univ Barcelona Fac Med Dept Physiol Sci Barcelona Spain Univ Toronto Hosp Sick Children Dept Pediat Lab Med Div Pathol Toronto ON Canada Univ Toronto Dept Lab Med & Pathobiol Toronto ON Canada Univ Texas Southwestern Med Ctr Dallas Adv Imaging Res Ctr Dallas TX 75390 USA Univ Texas Southwestern Med Ctr Dallas Dept Pharmacol Dallas TX USA Univ Barcelona Fac Med Dept Expt Pathol & Therapeut Barcelona Spain IDIBELL Barcelona Spain

Whole body cytosolic phosphoenolpyruvate carboxykinase knockout (pepck-C KO) mice die early after birth with profound hypoglycemia therefore masking the role of pepck-C in adult, non-gluconeogenic tissues where it is expressed. To investigate whether pepck-C deletion in the liver was critically responsible for the hypoglycemic phenotype, we reexpress this enzyme in the liver of pepck-C KO pups by early postnatal administration of pepck-Cexpressing adenovirus. This maneuver was sufficient to partially rescue hypoglycemia and allow the pups to survive and identifies the liver as a critical organ, and hypoglycemia as the critical pathomechanism, leading to early postnatal death in the whole-body pepck-C knockout mice. Pathology assessment of survivors also suggest a possible role for pepck-C in lung maturation and muscle metabolism.

关键词： pepck Gluconeogenesis Liver Neonatal hypoglycemia KO Hepatic lipidosis

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pepck-M recoups tumor cell anabolic potential in a PKC-ζ-dependent manner

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CANCER & METABOLISM 2021年第1期9卷 1-15页

作者： Hyrossova, Petra Arago, Marc Moreno-Felici, Juan Fu, Xiarong Mendez-Lucas, Andres Garcia-Roves, Pablo M. Burgess, Shawn Figueras, Agnes Vinals, Francesc Perales, Jose C. Univ Barcelona Sch Med Dept Physiol Sci Feixa Llarga S-N Lhospitalet De Llobregat 08907 Spain Univ Texas Dallas Ctr Human Nutr Dallas TX 75390 USA Univ Texas Dallas Dept Pharmacol Dallas TX 75390 USA IDIBELL Gran Via Hospitalet 199 Lhospitalet De Llobregat 08908 Spain

Background: Mitochondrial phosphoenolpyruvate carboxykinase (pepck-M;PCK2) is expressed in all cancer types examined and in neuroprogenitor cells. The gene is upregulated by amino acid limitation and ER-stress in an ATF4-dependent manner, and its activity modulates the PEP/Ca2+ signaling axis, providing clear arguments for a functional relationship with metabolic adaptations for cell survival. Despite its potential relevance to cancer metabolism, the mechanisms responsible for its pro-survival activity have not been completely elucidated. Methods: [U-C-13]glutamine and [U-C-13]glucose labeling of glycolytic and TCA cycle intermediates and their anabolic end-products was evaluated quantitatively using LC/MS and GC/MS in conditions of abundant glucose and glucose limitation in loss-of-function (shRNA) and gain-of-function (lentiviral constitutive overexpression) HeLa cervix carcinoma cell models. Cell viability was assessed in conjunction with various glucose concentrations and in xenografts in vivo. Results: pepck-M levels linearly correlated with [U-C-13]glutamine label abundance in most glycolytic and TCA cycle intermediate pools under nutritional stress. In particular, serine, glycine, and proline metabolism, and the anabolic potential of the cell, were sensitive to pepck-M activity. Therefore, cell viability defects could be rescued by supplementing with an excess of those amino acids. pepck-M silenced or inhibited cells in the presence of abundant glucose showed limited growth secondary to TCA cycle blockade and increased ROS. In limiting glucose conditions, downregulation of PKC-zeta tumor suppressor has been shown to enhance survival. Consistently, HeLa cells also sustained a survival advantage when PKC-zeta tumor suppressor was downregulated using shRNA, but this advantage was abolished in the absence of pepck-M, as its inhibition restores cell growth to control levels. The relationship between these two pathways is also highlighted by the anti-correlation ob

关键词： pepck pepck-M PCK2 Phosphoenolpyruvate carboxykinase Cancer metabolism PEP Phosphoenolpyruvate ER stress Amino acid deprivation PKC-zeta ATF4 Activating transcription factor 4 AAR Amino acid response GCN2 TCA cycle Cataplerosis Serine/glycine metabolism Proline metabolism PYCR PRODH/POX

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AMP-activated protein kinase regulates pepck gene expression by direct phosphorylation of a novel zinc finger transcription factor

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BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 2006年第4期351卷 793-799页

作者： Inoue, Erina Yamauchi, Jun Natl Inst Hlth & Nutr Bio Index Project Nutrit Epidemiol Program Bioindex ProjectShinjyuku Tokyo 1628636 Japan

AMP-activated protein kinase (AMPK) acts as an intracellular sensor for maintaining the energy balance. Activation of AMPK switches on ATP-generating process while switches off ATP-consuming process. It achieves these effects by phosphorylation of downstream metabolic enzymes. It has been proposed that AMPK also regulates gene expression through phosphorylation of certain transcription factors;however its molecular mechanism is not fully understood. Here we show the cloning and characterization of a novel zinc finger transcription factor referred to as AREBP. AREBP is phosphorylated at Ser(470) by AMPK. Phosphorylation reduces he DNA-binding activity of AREBP. Transient transfection experiments indicate that wild-type AREBP, but not Ser(470) to Ala(470) substituted non-phosphorylating mutant, represses gene expression of the phosphoenolpyruvate carboxykinase (pepck), a key enzyme of gluconeogenesis. RNA interference-mediated reduction of endogenous AREBP expression attenuates AMPK-induced pepck down-regulation. These results implicate AREBP as a novel key modulator of pepck gene expression regulated by AMPK. (c) 2006 Elsevier Inc. All rights reserved.

关键词： AMPK pepck gluconeogenesis zinc finger transcription RNAi

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A NUCLEAR-MAGNETIC-RESONANCE STUDY OF THE ROLE OF PHOSPHOENOL PYRUVATE CARBOXYKINASE (pepck) IN THE GLUCOSE-METABOLISM OF DIPETALONEMA-VITEAE

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MOLECULAR AND BIOCHEMICAL PARASITOLOGY 1987年第2期24卷 125-130页

作者： CHRISTIE, DA POWELL, JW STABLES, JN WATT, RA UNIV LONDON SCH PHARM DEPT PHARMACEUT CHEM LONDON WC1N 1AX ENGLAND

13C-NMR has been applied to the study of the metabolism of [1-13C]glucose by macrofilariae of Dipetalonema viteae under conditions of restricted glucose supply. In medium buffered with 13C-labelled bicarbonate, succinate labelled in the carboxyl position is formed in good yield. Quinolinic acid, a known inhibitor of phosphoenol pyruvate carboxykinase (pepck) has been shown to suppress the formation of labelled succinate from [1-13C]glucose. Both sets of experiments support the formation of succinate through the pepck-mediated carboxylation of phosphoenol pyruvate, followed by the operation of a partial tricarboxylic acid cycle.

关键词： NMR Dipetalonema viteae Phosphoenol pyruvate carboxykinase Quinolinic Acid Glucose metabolism Succinate NMR nuclear magnetic resonance pepck phosphoenol pyruvate carboxykinase PK pyruvate kinase TCA tricarboxylic acid

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DNA damage induces down-regulation of pepck and G6P gene expression through degradation of PGC-1α

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ACTA BIOCHIMICA ET BIOPHYSICA SINICA 2011年第8期43卷 589-594页

作者： Kim, Hyun-Ju Jee, Hye Jin Yun, Jeanho Dong A Univ Dept Biochem Coll Med Pusan 602714 South Korea

Hepatic gluconeogenesis plays a crucial role in glucose homeostasis. Although it is well established that various cellular processes are modulated by DNA damage, whether the DNA damage signaling pathway regulates gluconeogenesis has not yet been studied. In this study, we found that mRNA levels of phosphoenolpyruvate carboxykinase (pepck) and glucose-6-phosphatase (G6P), key enzymes for gluconeogenesis, were dramatically decreased upon IR- and UV-irradiation. pepck and G6P promoter activities were also suppressed by IR-and UV-irradiation, suggesting that pepck and G6P gene transcription are down-regulated upon DNA damage. We also found that the protein level of PGC-1 alpha, which is a critical transcription factor for pepck gene expression, is decreased upon UV-irradiation. The decreased PGC-1 alpha protein level was abolished by MG132, a potent proteasome inhibitor, suggesting that PGC-1 alpha is degraded through the ubiquitin-proteasome pathway upon UV-irradiation. These results reveal a novel link between glucose metabolism and the DNA damage signaling pathway and suggest a possible role for pepck and G6P in the DNA damage response.

关键词： DNA damage response pepck G6P PGC-1 alpha gluconeogenesis transcription regulation

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Early-life exposure to high-fat diet may predispose rats to gender-specific hepatic fat accumulation by programming pepck expression

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JOURNAL OF NUTRITIONAL BIOCHEMISTRY 2015年第5期26卷 433-440页

作者： Zhou, Dan Wang, Huan Cui, Hemiao Chen, Hong Pan, Yuan-Xiang Univ Illinois Dept Food Sci & Human Nutr Urbana IL 61801 USA Univ Illinois Div Nutr Sci Urbana IL 61801 USA Univ Illinois Illinois Informat Inst Urbana IL 61801 USA

Phosphoenolpyruvate carboxykinase (pepck) produces phosphoenolpyruvate during glyceroneogenesis. We previously demonstrated that a high-fat diet during pregnancy induced pepck mRNA expression in neonatal rat pups, which is characterized by histone modifications in specific regions of the gene (Strakovsky RS, Zhang X, Zhou D, Pan YX. Gestational high fat diet programs hepatic phosphoenolpyruvate carboxykinase gene expression and histone modification in neonatal offspring rats. The Journal of Physiology 2011;589:2707-17). In the present study, we investigated whether these alterations persistent in adult offspring. Dams were fed either control or high-fat diet throughout gestation and lactation. Offspring were placed on control diet after weaning, generating C/C and HF/C groups. Liver was collected at 12 weeks of age. Hepatic nicotinamide adenine dinucleotide (reduced) (NADH) level was increased in both genders, but fat accumulation occurred only in liver of female offspring in HF/C group. This was accompanied by a significant increase of pepck and fatty acid synthase (Fasn) mRNA expression in only female liver. The induction of pepck gene expression in females was associated with increased dimethylated histone H3 lysine 4 level in multiple regions of the gene. Meanwhile, acetylated histone H3 and trimethylated histone H3 lysine 4 were induced at a specific coding region in HF/C, accompanied by decreased trimethylated histone H3 lysine 9 level at the promoter of female offspring. In conclusion, maternal high-fat diet programs pepck expression through histone modifications in adult female offspring. Persistent pepck induction in females may contribute to increased triglyceride synthesis, together with induced Fasn expression and NADH levels, which may lead to increased fat deposition in a gender-specific manner. (C) 2015 Elsevier Inc. All rights reserved.

关键词： Epigenetic modification Maternal programming pepck Glyceroneogenesis Fatty liver

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miR-29a levels are elevated in the db/db mice liver and its overexpression leads to attenuation of insulin action on pepck gene expression in HepG2 cells

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MOLECULAR AND CELLULAR ENDOCRINOLOGY 2011年第1-2期332卷 125-133页

作者： Pandey, Amit K. Verma, Gaurav Vig, Saurabh Srivastava, Swayamprakash Srivastava, Arvind K. Datta, Malabika Inst Genom & Integrat Biol CSIR Delhi 110007 India Cent Drug Res Inst CSIR Lucknow 226001 Uttar Pradesh India

MicroRNAs comprise a class of small (similar to 22 nucleotide) non-coding RNA species and they bind to their complementary sequence on the 3'UTR of target genes and cause translational repression. In the present study, we report that miR-29a levels are significantly elevated in the diabetic db/db mice liver. Further, we report the effects of such elevation on insulin action in HepG2 cells. Overexpression of miR-29a narrowed down insulin mediated Akt phosphorylation without altering the total Akt levels presumably due to another upstream mediator being directly targeted by miR-29a. This hunt led us to the discovery that the p85 alpha subunit of PI3K (phosphoionositide-3-kinase), the upstream molecule in the insulin signaling cascade harbors the miR-29a binding site on its 3'UTR and a marked inhibition of PI3Kp85 alpha was observed by this microRNA. This was consequently accompanied by attenuation of insulin inhibition of pepck gene expression. All these events could be significantly prevented in the presence of the miR-29a inhibitor. Our results, for the first time, show the effect of miR-29a in counteracting insulin action on pepck gene expression by primarily targeting PI3K and abrogating downstream insulin signaling in HepG2 cells. (C) 2010 Elsevier Ireland Ltd. All rights reserved.

关键词： miR-29a pepck PI3K Diabetes Insulin

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Regulation of basal expression of hepatic pepck and G6Pase by AKT2

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BIOCHEMICAL JOURNAL 2020年第5期477卷 1021-1031页

作者： He, Lina Li, Yang Zeng, Ni Stiles, Bangyan L. Univ Southern Calif Sch Pharm Pharmacol & Pharmaceut Sci Los Angeles CA 90033 USA Univ Southern Calif Keck Sch Med Pathol Los Angeles CA 90033 USA

Hepatic glucose metabolism signaling downstream of insulin can diverge to multiple pathways including AKT. Genetic studies suggest that AKT is necessary for insulin to suppress gluconeogenesis. To specifically address the role of AKT2, the dominant liver isoform of AKT in the regulation of gluconeogenesis genes, we generated hepatocytes lacking AKT2 (Akt2(-/-)). We found that, in the absence of insulin signal, AKT2 is required for maintaining the basal level expression of phosphoenolpyruvate carboxyl kinase (pepck) and to a lesser extent G6Pase, two key rate-limiting enzymes for gluconeogenesis that support glucose excursion due to pyruvate loading. We further showed that this function of AKT2 is mediated by the phosphorylation of cyclic AMP response element binding (CREB). Phosphorylation of CREB by AKT2 is needed for CREB to induce the expression of pepck and likely represents a priming event for unstimulated cells to poise to receive glucagon and other signals. The inhibition of gluconeogenesis by insulin is also dependent on the reduced FOXO1 transcriptional activity at the promoter of pepck. When insulin signal is absent, this activity appears to be inhibited by AKT2 in manner that is independent of its phosphorylation by AKT. Together, this action of AKT2 on FOXO1 and CREB to maintain basal gluconeogenesis activity may provide fine-tuning for insulin and glucocorticoid/glucagon to regulate gluconeogenesis in a timely manner to meet metabolic needs.

关键词： AKT2 CREB FOXO1 G6Pase gluconeogenesis pepck

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Vitamin D improves the antidiabetic effectiveness of aerobic training via modulation of Akt, pepck, and G6Pase expression

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DIABETOLOGY & METABOLIC SYNDROME 2023年第1期15卷 1-9页

作者： Hoseini, Zahra Behpour, Nasser Hoseini, Rastegar Razi Univ Fac Sport Sci Dept Exercise Physiol POB *** Kermanshah Iran

BackgroundAlthough the effect of Vitamin D Supplementation (Vit D) on several chronic diseases has been well conceded, its role in diabetes remains ambiguous. The present study investigated the interactive effects of Aerobic Training (AT) and different Vit D doses on Protein Kinase B (Akt), Phosphoenolpyruvate Carboxylase (pepck), and Glucose-6-Phosphatase (G6Pase) protein expressions in hepatocytes of type-2 diabetic ***-six male Wistar rats were divided into 2 groups SHAM (non-diabetic control;n = 8), and diabetic (n = 48). Then, diabetic rats were divided into six groups: AT with high doses of Vit D (D + AT + HD), AT with moderate doses of Vit D (D + AT + MD), high doses of Vit D (D + HD), moderate doses of Vit D (D + MD), AT receiving vehicle (sesame oil;D + AT + oil), and control (oil-receiving). D + AT + HD and D + HD groups received 10,000 IU of Vit D;while D + AT + MD and D + MD groups receive 5000 IU of Vit D once a week by injection;D + AT + oil and SHAM groups received sesame oil. Diabetes was induced via intraperitoneal (IP) injection of streptozotocin (50 mg/kg body weight). After 2 months of intervention, serum insulin, glucose, and visceral fat were measured;protein expressions of Akt, pepck, and G6Pase were assessed by western blotting. The paired t-test, one-way analysis of variance (One-Way ANOVA), and the Tukey post hoc test were used at the signification level of P < *** data indicate that the diabeticization of rats increased the level of insulin, glucose, and pepck and G6Pase protein expressions and decreased the expression of the Akt (P < 0.05 for all variables). Combined AT and moderate or high Vit D significantly reduced body weight (P = 0.001;P = 0.001), body mass index (P = 0.001;P = 0.002), food intake (P = 0.001;P = 0.001) comparing the pre-test with the post-test, respectively. Also, AT and either high or moderate Vit D alone therapies lead to the improvement of the metabolic state, however, their combination h

关键词： Vitamin D Exercise Insulin resistance Akt pepck G6Pas

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