Expression and localization of an agmatinase-like protein in the rat brain

Abstract

Agmatinase catalyzes the hydrolysis of agmatine into putrescine and urea, and agmatine (decarboxylated L: -arginine) plays several roles in mammalian tissues, including neurotransmitter/neuromodulatory actions in the brain. Injection of agmatine in animals produces anticonvulsant, antineurotoxic and antidepressant-like actions. Information regarding the enzymatic aspects of agmatine metabolism in mammals, especially related to its degradation, is relatively scarce. The explanation for this is the lack of enzymatically active preparations of mammalian agmatinase. Recently, we have cloned a protein from a cDNA rat brain library having agmatinase activity although its amino acid sequence greatly differs from all known agmatinases, we called agmatinase-like protein. In this work, we analyzed the expression of this enzyme in the rat brain by means of RT-PCR and immunohistochemical analysis using a polyclonal antibody generated against the recombinant agmatinase-like protein. The agmatinase-like protein was detected in the hypothalamus in glial cells and arcuate nucleus neurons, and in hippocampus astrocytes and neurons, but not in brain cortex. In general, detected localization of agmatinase-like protein coincides with that described for its substrate agmatine and our results help to explain several reported effects of agmatine in the brain. Concretely, a role in the regulation of intracellular concentrations of the neurotransmitter/neuromodulator agmatine is suggested for the brain agmatinase-like protein.

Trypanosoma cruzi Coexpressing Ornithine Decarboxylase and Green Fluorescence Proteins as a Tool to Study the Role of Polyamines in Chagas Disease Pathology

“…In this context, the host ODC as well as the parasite uptake system would be potential targets, as by self or as a complementary target increasing the effect of antitrypanosomal therapies. As there has been some discrepancies about the possible presence of arginine decarboxylase (ADC) activity under specific metabolic conditions [41, 42, 65–68] as well as there are clear evidence about the presence of ADC in at least some kind of cells that could be infected by T. cruzi [27–29], this other possible way to obtain polyamines should be taken into account when the role of polyamines among the T. cruzi biological cycle is studied. In any case, the growth curves and the results obtained in metacyclogenesis assays support the idea that polyamines are engaged in parasite proliferation and in differentiation process.…”

“…Many plants, bacteria and some specific mammalian tissues possess an alternative pathway by arginine decarboxylase (ADC; EC 4.1.1.19) where arginine is converted to putrescine via the intermediate agmatine [25–29]. …”

Insight on the interaction of an agmatinase-like protein with Mn2+ activator ions

“…Considering that, in general, this localization coincides with that described for its substrate agmatine, ALP is likely to be involved in the regulation of intracellular concentrations of this neurotransmitter/ neuromodulator [13].…”

“…Using RT-PCR (reverse transcription polymerase chain reaction) and immunohistochemical methods it was shown that ALP is present in glial cells and arcuate nucleus neurons in the hypothalamus, as well as astrocytes and neurons in the hippocampus, but not in the brain cortex [13]. Considering that, in general, this localization coincides with that described for its substrate agmatine, ALP is likely to be involved in the regulation of intracellular concentrations of this neurotransmitter/ neuromodulator [13].…”

Histochemistry and cell biology: the annual review 2010

“…Due to the lack of enzymatically active preparations, information regarding to agmatine metabolism in the brain has been scarce. Therefore, Mella et al (2010) took up work on a recently identiWed protein (agmatinaselike protein) that displayed agmatinase activity (Uribe et al 2007). In the rat brain, the authors found that localization of this protein (restricted to the hypothalamus and the hippocampus) coincided with that described for its substrate.…”