Functional Characterization of Hypertrehalosemic Hormone Receptor in Relation to Hemolymph Trehalose and to Oxidative Stress in the Cockroach Blattella germanica

Abstract

Hypertrehalosemic hormone (HTH) is a peptide hormone that belongs to the adipokinetic hormone/red pigment concentrating hormone (AKH/RPCH) family, which exerts pleiotropic actions related to catabolic reaction and stress response. AKH peptides have been demonstrated to participate in stress response including oxidative stress in several insects. In order to study the signaling pathway of HTH involved in anti-oxidative stress, we have characterized a HIH receptor cDNA in Blattella germanica (Blage-HTHR) in structural and in functional terms using RNA interference (RNAi). Blage-HTHR is expressed in various female adult tissues (brain–CC–CA, ventral nerve cord, midgut, fat body, oviduct), but maximal expression is observed in the fat body. RNAi-mediated knockdown of Blage-HTHR expression results in a significantly lower level of hemolymph trehalose, even though HTH is exogenously administered. Paraquat elicits lethal oxidative stress in B. germanica, and co-injection of paraquat and HTH reduces this detrimental effect and extends the median survival time. Interestingly, the “rescue” effect of HTH on mortality caused by paraquat is diminished in specimens with depleted expression of Blage-HTH and Blage-HTHR. Finally, lipid peroxidation in the hemolymph increases 4 h after paraquat treatment, in comparison with control specimens or with HTH-treated specimens. However, lipid peroxidation induced by paraquat was not “rescued” by HTH in Blage-HTH and Blage-HTHR knockdown specimens. Our results demonstrate that HTH acts as a stress hormone mediating anti-oxidative protection in B. germanica, and that its receptor, Blage-HTHR, is essential for this action.

FoxO is required for the activation of hypertrehalosemic hormone expression in cockroaches

“…In the case of the muscle, we haven't found differences in BgGlyP mRNA which indicates that BgFoxO does not have the same effect in this tissue. In addition, extremely low AKH/HTH receptor levels have been reported in muscle compared to fat body in all the insects for which this has been studied [40][41][42]. All these results explain why we haven't found significant differences in muscle glycogen content between control and dsFoxO starved females.…”

Adipokinetic hormones control amylase activity in the cockroach (Periplaneta americana) gut

“…Finally, a study in S. crassipalpis confirmed the role of AKH in insect digestion; AKH injection into decapitated flies enhanced midgut proteolytic activity up to the level of intact flies (Bil et al ., ). Furthermore, studies examining AKHR have demonstrated that the receptor is expressed in the insect gut, indirectly confirming the importance of AKH in insect digestion ( P. americana , Wicher et al ., ; Manduca sexta , Ziegler et al ., ; Blattella germanica , Huang et al ., ).…”

More than two decades of research on insect neuropeptide GPCRs: an overview

“…The last years it became clear that the function of AKH is not restricted to locomotory activity alone, but that it acts as a general regulator of homeostasis in insects, influencing all energy requiring processes (e.g., egg production, feeding behavior, larval growth, molting, and immune response) (Goldsworthy et al, 2002, 2003; Lorenz, 2003; Lee and Park, 2004; Isabel et al, 2005; Grönke et al, 2007; Bharucha et al, 2008; Lorenz and Gäde, 2009; Arrese and Soulages, 2010; Attardo et al, 2012; Konuma et al, 2012). AKH also serves as an anti-stress hormone in oxidative stress situations (Kodrík et al, 2007; Večeřa et al, 2007; Kodrík, 2008; Huang et al, 2011a). …”