TY - JOUR
T1 - Transgenic mice with elevated level of CuZnSOD are highly susceptible to malaria infection
AU - Golenser, Jacob
AU - Peled-Kamar, Mira
AU - Schwartz, Eli
AU - Friedman, Ilanit
AU - Groner, Yoram
AU - Pollack, Yaakov
N1 - Funding Information:
We thank Yehudit Hermesh for skillful technical assistance in maintenance and analysis of Tg-CuZnSOD mice. The research was partly supported by grants #565/91 from the Israel Academy of Sciences and Humanities; #1 from the Beryl and Frances Weinstein Foundation, as well as by grants from the National Institutes of Health (USA), the Shapell Family Biomedical Research Foundation, and the Weizmann Institute’s Forchheimer Center of Molecular Genetics.
PY - 1998/6
Y1 - 1998/6
N2 - Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2·- into H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of CuZnSOD to determine whether overexpression of CuZnSOD affected the susceptibility of these mice to plasmodium infection Acute malaria is associated with oxidative stress, mediated by redox-active iron released from the infected RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD mice were more vulnerable than control mice, the levels of parasitemia were comparable in both strains. Moreover, treatment of infected red blood cells (RBC) with oxidative stress inducers, such as ascorbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC. This further confirms that increased CuZnSOD does not support plasmodia development. The data are consistent with the possibility that the combination of increased redox- active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to an enhanced Fenton's reaction-mediated HO· production, and the resulting oxidative injury renders the transgenic mice more vulnerable to parasite infection.
AB - Copper/zinc superoxide dismutase (CuZnSOD) catalyses the conversion of O2·- into H2O2. Constitutive overexpression of CuZnSOD in cells and animals creates an indigenous oxidative stress that predisposes them to added insults. In this study, we used transgenic CuZnSOD (Tg-CuZnSOD) mice with elevated levels of CuZnSOD to determine whether overexpression of CuZnSOD affected the susceptibility of these mice to plasmodium infection Acute malaria is associated with oxidative stress, mediated by redox-active iron released from the infected RBC. Two independently derived Tg-CuZnSOD lines showed higher sensitivity than control mice to infection by Plasmodium berghei (P. berghei), reflected by an earlier onset and increased rate of mortality. Nevertheless, while Tg-CuZnSOD mice were more vulnerable than control mice, the levels of parasitemia were comparable in both strains. Moreover, treatment of infected red blood cells (RBC) with oxidative stress inducers, such as ascorbate or paraquat, reduced the viability of parasites equally in both transgenic and control RBC. This further confirms that increased CuZnSOD does not support plasmodia development. The data are consistent with the possibility that the combination of increased redox- active iron and elevated H2O2 in the plasmodium-infected Tg-CuZnSOD mice, led to an enhanced Fenton's reaction-mediated HO· production, and the resulting oxidative injury renders the transgenic mice more vulnerable to parasite infection.
KW - Fenton's reaction
KW - Free radical
KW - Malaria
KW - Oxidative stress
KW - Plasmodium
KW - Redox-active iron
KW - Transgenic-CuZnSOD mice
UR - http://www.scopus.com/inward/record.url?scp=0031811263&partnerID=8YFLogxK
U2 - 10.1016/S0891-5849(98)00026-4
DO - 10.1016/S0891-5849(98)00026-4
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C2 - 9641269
AN - SCOPUS:0031811263
SN - 0891-5849
VL - 24
SP - 1504
EP - 1510
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 9
ER -