Expression of antizyme inhibitor 2 in male haploid germinal cells suggests a role in spermiogenesis

López-Contreras, Andrés J.; Ramos‐Molina, Bruno; Martı́nez-de-la-Torre, Margaret; Peñafiel-Verdú, C.; Puelles, Luis; Cremades, Adolfo Díaz-Bautista; Peñafiel, Rafael

doi:10.1016/j.biocel.2008.09.029

Cited by 21 publications

(30 citation statements)

References 52 publications

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“…This localization of antizyme-3 is different from that of ornithine decarboxylase mRNA, which is found mainly in the outer part of the seminiferous tubules where spermatogonia and spermatocytes are located [88]. This observation may be compatible with a recent study demonstrating that in contrast to its ability to inhibit ODC and polyamine uptake, antizyme-3 does not target ODC to degradation [85].…”

Section: Antizymesupporting

confidence: 63%

“…Antizyme inhibitor 2 and antizyme 3 are both expressed in the haploid germinal cells, a location different from that of ODC mRNA, which localizes predominantly to the outer part of the seminiferous tubules. In addition, antizyme inhibitor 2 and antizyme 3 are expressed at minimal levels during the three first postnatal weeks, and are highly induced in the fourth week [88]. These results suggest that antizyme inhibitor 2 and antizyme 3 may have a role in spermiogenesis.…”

Section: Antizyme Inhibitormentioning

confidence: 73%

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Antizyme and antizyme inhibitor, a regulatory tango

Kahana

2009

Cell. Mol. Life Sci.

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The polyamines are small basic molecules essential for cellular proliferation and viability. An autoregulatory circuit that responds to the intracellular level of polyamines regulates their production. In the center of this circuit is a family of small proteins termed antizymes. Antizymes are themselves regulated at the translational level by the level of polyamines. Antizymes bind ornithine decarboxylase (ODC) subunits and target them to ubiquitin-independent degradation by the 26S proteasome. In addition, antizymes inhibit polyamine transport across the plasma membrane via an as yet unresolved mechanism. Antizymes may also interact with and target degradation of other growth-regulating proteins. An inactive ODC-related protein termed antizyme inhibitor regulates polyamine metabolism by negating antizyme functions. The ability of antizymes to degrade ODC, inhibit polyamine uptake and consequently suppress cellular proliferation suggests that they act as tumor suppressors, while the ability of antizyme inhibitors to negate antizyme function indicates their growth-promoting and oncogenic potential.

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Section: Antizymesupporting

confidence: 63%

Section: Antizyme Inhibitormentioning

confidence: 73%

Antizyme and antizyme inhibitor, a regulatory tango

Kahana

2009

Cell. Mol. Life Sci.

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“…OAZ3 deficient mice produce aberrant sperm that are incapable of fertilization because of defects in sperm motility [52]; OAZ3 is a potent inhibitor of ODC in spermiogenesis [53],[54]. Moreover, AZIN2, which blocks the inhibitory effects of OAZ3 on ODC, is abundant in haploid cells [55],[56]. Gene expression profiles of Lrp6- deficient versus wild-type mice on control versus FA-supplemented diets show differences for several genes involved in polyamine synthesis, namely Odc1, Sat1 – spermine/spermidine N-acetyl N1-transferase 1, and Oaz1 - ornithine decarboxylase antizyme 1 – another ODC inhibitor [24].…”

Section: Discussionmentioning

confidence: 99%

Does dietary folic acid supplementation in mouse NTD models affect neural tube development or gamete preference at fertilization?

Nakouzi

Nadeau

2014

BMC Genet

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BackgroundNeural tube defects (NTDs) are the second most common birth defect in humans. Dietary folic acid (FA) supplementation effectively and safely reduces the incidence of these often debilitating congenital anomalies. FA plays an established role in folate and homocysteine metabolism, but the means by which it suppresses occurrence of NTDs is not understood. In addition, many cases remain resistant to the beneficial effects of folic acid supplementation. To better understand the molecular, biochemical and developmental mechanisms by which FA exerts its effect on NTDs, characterized mouse models are needed that have a defined genetic basis and known response to dietary supplementation.ResultsWe examined the effect of FA supplementation, at 5-fold the level in the control diet, on the NTD and vertebral phenotypes in Apob tm1Unc and Vangl2 Lp mice, hereafter referred to as Apob and Lp respectively. The FA supplemented diet did not reduce the incidence or severity of NTDs in Apob or Lp mutant homozygotes or the loop-tail phenotype in Lp mutant heterozygotes, suggesting that mice with these mutant alleles are resistant to FA supplementation. Folic acid supplementation also did not affect the rate of resorptions or the size of litters, but instead skewed the embryonic genotype distribution in favor of wild-type alleles.ConclusionSimilar genotypic biases have been reported for several NTD models, but were interpreted as diet-induced increases in the incidence and severity of NTDs that led to increased embryonic lethality. Absence of differences in resorption rates and litter sizes argue against induced embryonic lethality. We suggest an alternative interpretation, namely that FA supplementation led to strongly skewed allelic inheritance, perhaps from disturbances in polyamine metabolism that biases fertilization in favor of wild-type gametes.

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“…Although the presence of Azin2 mRNA in mouse spermatids suggested that AZIN2 may have a role in spermiogenesis [19], other studies showing AZIN2 immunoreactivity in mast cells [20] as well as in Leydig cells and ovarian luteinized cells [21] have related AZIN2 with the release of serotonin and steroid hormones. In addition, our studies using real-time RT-PCR detected significant Azin2 mRNA levels in several mouse tissues, including pancreas and adrenal glands, similar to those existing in brain [22].…”

Section: Introductionmentioning

confidence: 97%

Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

et al. 2013

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The intracellular levels of polyamines, polycations implicated in proliferation, differentiation and cell survival, are regulated by controlling their biosynthesis, catabolism and transport. Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase, the rate-limiting biosynthetic enzyme, and polyamine uptake. We recently described the molecular function of a novel antizyme inhibitor (AZIN2). However, the physiological function of AZIN2 in mammals is mostly unknown. To gain insight on the tissue expression profile of AZIN2 and to find its possible physiological role, we have generated, transgenic mice with severe Azin2 hypomorphism. This mouse model expresses transgenic bacterial β-D-galactosidase as a reporter gene, under the control of the Azin2 endogenous promoter, what allows a very sensitive and specific detection of the expression of the gene in the different tissues of transgenic mice. The biochemical and histochemical analyses of β-D-galactosidase together with the quantification of Azin2 mRNA levels, corroborated that AZIN2 is mainly expressed in testis and brain, and showed for the first time that AZIN2 is also expressed in the adrenal glands and pancreas. In these tissues, AZIN2 was not expressed in all type of cells, but rather in specific type of cells. Thus, AZIN2 was mainly found in the haploid germinal cells of the testis and in different brain regions such as hippocampus and cerebellum, particularly in specific type of neurons. In the adrenal glands and pancreas, the expression was restricted to the adrenal medulla and to the Langerhans islets, respectively. Interestingly, plasma insulin levels were significantly reduced in the transgenic mice. These results support the idea that AZIN2 may have a role in the modulation of reproductory and secretory functions and that this mouse model might be an interesting tool for the progress of our understanding on the role of AZIN2 and polyamines in specific mammalian cells.

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Expression of antizyme inhibitor 2 in male haploid germinal cells suggests a role in spermiogenesis

Cited by 21 publications

References 52 publications

Antizyme and antizyme inhibitor, a regulatory tango

Antizyme and antizyme inhibitor, a regulatory tango

Does dietary folic acid supplementation in mouse NTD models affect neural tube development or gamete preference at fertilization?

Antizyme Inhibitor 2 Hypomorphic Mice. New Patterns of Expression in Pancreas and Adrenal Glands Suggest a Role in Secretory Processes

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