Expression of Hexokinase 1 and Hexokinase 2 in Mammary Tissue of Nonlactating and Lactating Rats: Evaluation by RT–PCR

Kaselonis, Gary L; McCabe, Edward R.B.; Gray, S. M.

doi:10.1006/mgme.1999.2923

Cited by 17 publications

(19 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…providing Glc-6-P for resynthesis of glycogen during recovery of skeletal muscle after contraction. More recent work is also consistent with an anabolic role for the Type II isozyme as a source of Glc-6-P for metabolism via the pentose phosphate pathway, providing NADPH required for lipid synthesis in liver (Sebastian et al, 2000) or lactating mammary gland (Kaselonis et al, 1999). By this same reasoning, the similarity in response of the Type II and Type III isozymes to Glc-6-P and Pi (Table·1) suggests that the latter isozyme may also have primarily an anabolic role, but presently there is no basis for associating the Type III isozyme with a particular anabolic pathway (or pathways).…”

Section: Isozymes Of Mammalian Hexokinasesupporting

confidence: 58%

Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function

Wilson

2003

Journal of Experimental Biology

942

905

View full text Add to dashboard Cite

SUMMARY The first step in metabolism of glucose (Glc) is usually phosphorylation,catalyzed by hexokinase. However, the Glc-6-P produced can then enter one or more of several alternative pathways. Selective expression of isozymic forms of hexokinase, differing in catalytic and regulatory properties as well as subcellular localization, is likely to be an important factor in determining the pattern of Glc metabolism in mammalian tissues/cells. Despite their overall structural similarity, the Type I, Type II and Type III isozymes differ in important respects. All three isozymes are inhibited by the product,Glc-6-P, but with the Type I isozyme, this inhibition is antagonized by PI, whereas with the Type II and Type III isozymes, Piactually causes additional inhibition. Reciprocal changes in intracellular levels of Glc-6-P and Pi are closely associated with cellular energy status, and it is proposed that the response of the Type I isozyme to these effectors adapts it for catabolic function, introducing Glc into glycolytic metabolism for energy production. In contrast, the Type II, and probably the Type III, isozymes are suggested to serve primarily anabolic functions, e.g. to provide Glc-6-P for glycogen synthesis or metabolism via the pentose phosphate pathway for lipid synthesis. Type I hexokinase binds to mitochondria through interaction with porin, the protein that forms channels through which metabolites traverse the outer mitochondrial membrane. Several experimental approaches have led to the conclusion that the Type I isozyme, bound to actively phosphorylating mitochondria, selectively uses intramitochondrial ATP as substrate. Such interactions are thought to facilitate coordination of the introduction of Glc into glycolysis, via the hexokinase reaction, with the terminal oxidative stages of Glc metabolism occurring in the mitochondria, thus ensuring an overall rate of Glc metabolism commensurate with cellular energy demands and avoiding excessive production of lactate. The Type II isozyme also binds to mitochondria. Whether such coupling occurs with mitochondrially bound Type II hexokinase in normal tissues, and how it might be related to the proposed anabolic role of this isozyme, remain to be determined. The Type III isozyme lacks the hydrophobic N-terminal sequence known to be critical for binding of the Type I and Type II isozymes to mitochondria. Immunolocalization studies have indicated that, in many cell types, the Type III has a perinuclear localization, the possible metabolic consequences of which remain unclear.

show abstract

Section: Isozymes Of Mammalian Hexokinasesupporting

confidence: 58%

Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function

Wilson

2003

Journal of Experimental Biology

942

905

View full text Add to dashboard Cite

show abstract

“…It was observed that BMEC grown in higher glucose concentrations (5, 10 and 20 mM) had higher HK activities, which confirmed the previous assumption and agreed with Yamada et al (2005), who reported that HK activities showed positive relationship with glucose uptake. As both HK1 and HK2 were expressed in lactating rat mammary gland (Kaselonis et al, 1999), and it is interesting to define the specific role each HK played in the BMEC, the expression of HK1 mRNA could not be detected, whereas the HK2 was expressed at a relatively high level in the BMEC. As HK2 is involved in the process of anabolism (Sebastian et al, 2000;Southworth et al, 2007), the above results suggest that HK2 may play an important role in milk synthesis in the lactating bovine mammary gland.…”

Section: Discussionmentioning

confidence: 99%

“…Each of the HKs has tissue-specific patterns of expression and differs in catalytic and regulatory properties (Wilson, 2003). Both HK1 and HK2 are reported to be expressed in lactating rat mammary gland (Kaselonis et al, 1999); however, the expression profile of HKs in lactating bovine mammary gland is still unclear.…”

Section: Introductionmentioning

confidence: 99%

Effect of glucose availability on glucose transport in bovine mammary epithelial cells

Zhao

Liu

Wang

et al. 2012

Animal

View full text Add to dashboard Cite

Primary bovine mammary epithelial cells (BMEC) were cultured in media containing varying concentrations of glucose, to determine the effects of glucose availability on glucose transport and its mechanism in bovine mammary gland. The BMEC incubated with 10 and 20 mM glucose had twofold greater glucose uptake than that with 2.5 mM glucose (P , 0.05). Increased glucose availability enhanced the cell proliferation (P , 0.05). As the glucose uptake is mediated by facilitative glucose transporters (GLUTs), the expression of GLUT mRNA was investigated. Compared with the control (2.5 mM), 5 and 10 mM glucose did not influence the abundance of GLUT1 mRNA (P , 0.05), whereas 20 mM glucose decreased the GLUT1 mRNA expression in the BMEC (P , 0.05). The expression of GLUT8 mRNA was not affected by any concentration of glucose (P . 0.05). As GLUTs are coupled with hexokinases (HKs) in regulating glucose uptake, the expression of HKs and their activities were also studied. The HK activity was greater in 5, 10 and 20 mM glucose than that in 2.5 mM glucose (P , 0.05). The expression of HK2 mRNA rather than HK1 mRNA was detected in the BMEC; however, the abundance of HK2 mRNA was not elevated by any concentrations of glucose compared with control (P . 0.05). Furthermore, addition of 3-bromopyruvate (30, 50 or 70 mM), an inhibitor of HK2, resulted in the decrease of glucose uptake and cell proliferation at both 2.5 and 10 mM glucose (P , 0.05). Therefore, the glucose concentrations may affect glucose uptake partly by altering the activity of HKs, and HK2 may play an important role in the regulation of glucose uptake in the BMEC.

show abstract

“…Key events underlying these dramatic changes in milk composition and volume include closure of the epithelial cell tight junctions, upregulation of milk protein synthesis, upregulation of lactose and lipid synthesis, and increased oxidative metabolism (Mellenberger & Bauman 1974a,b, Rosen et al 1978, Nguyen et al 2001. Along with these, increases also occur in the expression and/or activation of enzymes associated with glucose metabolism such as hexokinase II, Glut 1, Glut 12, and PFK2 (Sochor et al 1984, Kaselonis et al 1999, Nemeth et al 2000, Macheda et al 2003. Although the underlying trigger for these events is not completely understood, key events involved with lactogenesis include the drop in blood progesterone that coincides with parturition along with surges in blood prolactin and glucocorticoids .…”

Section: Introductionmentioning

confidence: 99%

Decreased lactation capacity and altered milk composition in insulin receptor substrate null mice is associated with decreased maternal body mass and reduced insulin-dependent phosphorylation of mammary Akt

Hadsell

Olea²,

Lawrence³

et al. 2007

Journal of Endocrinology

View full text Add to dashboard Cite

Expression of insulin receptor substrates (IRS)-1 and -2 within the mammary gland was found to be high at midlactation and dramatically decreased with mammary involution. This observation supports the hypothesis that these proteins are induced in the mammary gland with lactogenesis and involved in normal milk synthesis. To test this hypothesis, lactation capacity, along with indices of mammary secretory cell glucose metabolism and cell signaling were compared in normal mice and mice carrying targeted mutations in either the Irs1 or Irs2 genes. Mammary IRS-1 and IRS-2 protein levels were increased within 1 day of parturition and reached maximal levels by 5 days post partum. Dams carrying germline mutations of Irs1 or Irs2 displayed reduced lactation capacity as assessed by weight gain of pup litters. The reduction was more dramatic in Irs1 K/K versus Irs2 K/K dams. Maternal body weight was also reduced in Irs1 K/K dams as well as in Irs1 Irs2C/K dams. The loss of IRS-1 had little impact on mammary gland expression of milk protein mRNAs, glucose transport, or on the abundance and subcellular localization of hexokinases I and II. The loss of IRS-1 was associated with a compensatory increase in insulin-induced IRS-2 phosphorylation; however, the loss of IRS-1 did also cause a reduction in insulin-dependent mammary gland-specific activation of Akt phosphorylation. These results support the conclusion that IRS-1 is important for insulin-dependent activation of Akt signaling within the lactating mammary gland, but that loss of this protein has only modest impact on normal milk synthesis, since related signaling proteins such as IRS-2 may act in compensatory fashion.

show abstract

Expression of Hexokinase 1 and Hexokinase 2 in Mammary Tissue of Nonlactating and Lactating Rats: Evaluation by RT–PCR

Cited by 17 publications

References 18 publications

Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function

Isozymes of mammalian hexokinase: structure, subcellular localization and metabolic function

Effect of glucose availability on glucose transport in bovine mammary epithelial cells

Decreased lactation capacity and altered milk composition in insulin receptor substrate null mice is associated with decreased maternal body mass and reduced insulin-dependent phosphorylation of mammary Akt

Contact Info

Product

Resources

About