Sn-protoporphyrin inhibits both heme degradation and hemozoin formation in Rhodnius prolixus midgut

• Published in: Insect biochemistry and molecular biology Vol. 40; no. 12; pp. 855 - 860
• Main Authors: Caiaffa, C.D., Stiebler, R., Oliveira, M.F., Lara, F.A., Paiva-Silva, G.O., Oliveira, P.L.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2010
• Subjects: Animals; antioxidant activity; biliverdin; binding proteins; biochemical pathways; biosynthesis; Blood; defense mechanisms; degradation; enzyme activity; Female; Gastrointestinal Tract - metabolism; hematophagous insects; Hematophagy; Heme; Heme - metabolism; Heme oxygenase; heme-binding protein; Hemeproteins - metabolism; hemolymph; hemozoin; inhibitors; insect biochemistry; metabolic detoxification; Metalloporphyrins - metabolism; midgut; Oviposition; Oxidative stress; oxygenases; protoporphyrin; Protoporphyrins - metabolism; Rabbits; Rhodnius - physiology; Rhodnius prolixus; Sn-protoporphyrin; toxic substances; Oxidative stress; Rhodnius prolixus; Heme; Heme oxygenase; Hematophagy
• ISSN: 0965-1748; 1879-0240
• DOI: 10.1016/j.ibmb.2010.08.005

Hematophagy is a feeding habit that involves the ingestion of huge amounts of heme. The hematophagous hemipteran
Rhodnius prolixus evolved many genetic resources to protect cells against heme toxicity. The primary barrier against the deleterious effects of heme is the aggregation of heme into hemozoin in the midgut lumen. Hemozoin formation is followed by the enzymatic degradation of heme by means of a unique pathway whose end product is dicysteinyl-biliverdin IX-γ (
Rhodnius prolixus biliverdin, RpBv). These mechanisms are complemented by a heme-binding protein (RHBP) in the hemolymph that attenuates the pro-oxidant effects of heme. In this work, we show that when insects are fed with blood enriched with a heme analog, Sn-protoporphyrin (SnPP-IX), both hemozoin synthesis and RpBv production are inhibited in a dose-dependent manner. These effects are accompanied by increased oxidative damage to the midgut epithelium and inhibition of oviposition, indicating that hemozoin formation and heme degradation are protective mechanisms that work together and contributed to the adaptation of this insect to successfully feed on vertebrate blood.
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►Heme is degraded to dicysteinyl-biliverdin IX γ in
Rhodnius midgut. ►Heme degradation pathway in the gut has five steps, as in the heart of the insect. ►Heme detoxification also is accomplished by heme aggregation into hemozoin. ►Sn-protoporphyrin inhibits both mechanisms o heme detoxification in the gut. ►Inhibition of both pathways leads to oxidative stress and inhibition of egg growth.