Jaburetox, a urease‐derived peptide: Effects on enzymatic pathways of the cockroach Nauphoeta cinerea

Abstract

Jaburetox is a recombinant peptide derived from one of the Canavalia ensiformis urease isoforms. This peptide induces several toxic effects on insects of different orders, including interference on muscle contractility in cockroaches, modulation of UDP‐N‐acetylglucosamine pyrophosphorylase (UAP) and nitric oxide synthase (NOS) activities in the central nervous system of triatomines, as well as activation of the immune system in Rhodnius prolixus. When injected, the peptide is lethal for R. prolixus and Triatoma infestans. Here, we evaluated Jaburetox toxicity to Nauphoeta cinerea cockroaches, exploring the effects on the central nervous system through the activities of UAP, NOS, acid phosphatases (ACP), and acetylcholinesterase (AChE). The results indicated that N. cinerea is not susceptible to the lethal effect of the peptide. Moreover, both in vivo and in vitro treatments with Jaburetox inhibited NOS activity, without modifying the protein levels. No alterations on ACP activity were observed. In addition, the enzyme activity of UAP only had its activity affected at 18 hr after injection. The peptide increased the AChE activity, suggesting a mechanism involved in overcoming the toxic effects. In conclusion, our findings indicate that Jaburetox affects the nitrinergic signaling as well as the AChE and UAP activities and establishes N. cinerea as a Jaburetox‐resistant model for future comparative studies.

Structure-Function Insights of Jaburetox and Soyuretox: Novel Intrinsically Disordered Polypeptides Derived from Plant Ureases

“…In N. cinerea, this effect was amplified by chloral hydrate, (a drug known to reinforce effects mediated by GABA receptors), suggesting that Jaburetox could be activating the gabaergic neurotransmission [85]. As reported in the kissing bugs, the enzymatic activities of several enzymes were modulated in adult cockroaches upon injection [86].…”

“…Nevertheless, the effect of Jaburetox was different on the activity of NOS in the salivary glands and hemocytes, where the expression of its gene was increased, indicating an organ-specific effect [78]. Jaburetox-induced alterations of NOS is not restricted to triatomines, since the peptide also induced a decrease in NOS enzyme activity in the central nervous system of the cockroach N. cinerea, upon in vivo or in vitro treatments, without affecting the protein expression [86]. The regulation of NO production mediated by Jaburetox is complex and could involve more than one level, for example, affecting directly the enzyme as the in vitro assays pointed out and/or, indirectly, through modifications on the expression of its gene, or even altering the membrane properties of target cells [77].…”

“…There are less information available for Soyuretox, although the effect of a dose comparable to those employed with Jaburetox also resulted lethal in D. peruvianus [64]. The only exception to this trend so far has been the cockroach Nauphoeta cinerea, since feeding or injecting Jaburetox did not result in mortality [86]. As we will discuss later, the effect on the activities of the central nervous system enzymes was different in cockroaches of this species when compared to susceptible insects such as the kissing bug R. prolixus.…”

“…The profile of UAP modulation by the Jaburetox in N. cinerea was different, since its activity was only affected 18 h after injection. This distinct response when compared to the triatomines could be related to the fact that this cockroach is so far the only species found to be resistant to the acute lethal effect of Jaburetox [86]. As the activity of acetylcholinesterase, an enzyme involved in the resistance of insects to organic pesticides, increased upon treatment of the cockroach with Jaburetox, the lack of lethality could be a reflex of an analogous mechanism(s) disabling the toxic effects of the peptide [86].…”

“…This distinct response when compared to the triatomines could be related to the fact that this cockroach is so far the only species found to be resistant to the acute lethal effect of Jaburetox [86]. As the activity of acetylcholinesterase, an enzyme involved in the resistance of insects to organic pesticides, increased upon treatment of the cockroach with Jaburetox, the lack of lethality could be a reflex of an analogous mechanism(s) disabling the toxic effects of the peptide [86]. However, Jaburetox is far from being innocuous to N. cinerea, as the paralyzing effect and alterations in behavior caused by the peptide could lead to death as well, due to inability to hide and avoid danger, or to find food.…”