Knockout Mouse Models for Peroxiredoxins

Abstract

Peroxiredoxins (PRDXs) are members of a highly conserved peroxidase family and maintain intracellular reactive oxygen species (ROS) homeostasis. The family members are expressed in most organisms and involved in various biological processes, such as cellular protection against ROS, inflammation, carcinogenesis, atherosclerosis, heart diseases, and metabolism. In mammals, six PRDX members have been identified and are subdivided into three subfamilies: typical 2-Cys (PRDX1, PRDX2, PRDX3, and PRDX4), atypical 2-Cys (PRDX5), and 1-Cys (PRDX6) subfamilies. Knockout mouse models of PRDXs have been developed to investigate their in vivo roles. This review presents an overview of the knockout mouse models of PRDXs with emphases on the biological and physiological changes of these model mice.

Mitochondrial hydrogen peroxide positively regulates neuropeptide secretion during diet-induced activation of the oxidative stress response

“…One explanation, termed the "floodgate hypothesis", proposes that when H 2 O 2 levels increase beyond a certain threshold, peroxiredoxins become hyperoxidized and are inactivated allowing H 2 O 2 to build up sufficiently to perform its signaling functions 161,162 163,164 , suggesting that it may play a major role in mitochondrial redox signaling. Mouse peroxiredoxin 3 knockouts appear largely healthy, but have increased mtH 2 O 2 levels, and have defects in mitochondrial and metabolic homeostasis in a number of tissues 165 , whereas overexpression of peroxiredoxin 3 results in decreased ROS levels 166 . Peroxiredoxin 3 and thioredoxin 2 are expressed broadly in the nervous system, where they have well documented roles in neuroprotection in response to oxidative damage in hippocampal and cortical neurons [167][168][169] .…”

MicroRNA-383 promotes reactive oxygen species-induced autophagy via downregulating peroxiredoxin 3 in human glioma U87 cells

“…The majority of PRDX3 is localized in the mitochondria ( 27 ); however, PRDX3 expression on the cell membrane has been shown to be regulated by androgens in LNCaP cells, which is a prostate cancer cell line ( 28 ). PRDX3 is a member of the peroxiredoxin family, which is responsible for neutralizing ROS ( 29 ), has been reported to be upregulated in a specific endocrine-regulated tumor (prostate cancer) ( 24 ). In androgen-resistant LNCaP cells, PRDX3 protein expression levels have been indicated to be upregulated, thereby preventing H 2 O 2 -induced apoptosis, while PRDX3 knockout has been demonstrated to restore the sensitivity of H 2 O 2 -induced apoptosis.…”

Dimethyl Fumarate, an Approved Multiple Sclerosis Treatment, Reduces Brain Oxidative Stress in SIV-Infected Rhesus Macaques: Potential Therapeutic Repurposing for HIV Neuroprotection

“…DMF targets the Nrf2/ARE pathway, which involves multiple genes that protect cells from oxidative stress and injury [ 37 , 54 , 55 , 56 , 57 , 58 , 59 ], including antioxidant enzymes, such as NQO1 [ 60 ], GPX1 [ 61 ], PRDX1 [ 62 ], and HO-1 [ 63 ]. We quantified the antioxidant enzyme expression in eleven brain regions ( Figure 4 ), as well as the spleen ( Figure 5 ), thymus, and liver ( Figure S1 ), and observed higher NQO1 ( p < 0.01), GPX1 ( p < 0.001), and HO-1 ( p < 0.05) expression in the brains of DMF-treated animals compared to untreated animals (via comparing the means of expression from each region in each group using a paired t -test, Figure 4 B,D,F,H,J).…”