Mitochondrion-associated protein peroxiredoxin 3 promotes benign prostatic hyperplasia through autophagy suppression and pyroptosis activation

Abstract

Benign prostatic hyperplasia (BPH) is one of the most common diseases in the senior men and age plays an important role in the initiation and development of BPH. Mammalian cells primarily use the autophagy-lysosome system to degrade misfolded/aggregated proteins and dysfunctional organelles such as mitochondria and suppress pyroptosis, a type of cell death that stimulates inflammatory responses and growth of other cells around. Peroxiredoxin 3 (PRDX3) is the only mitochondrion-associated member of peroxiredoxin family enzymes that exert their protective antioxidant role in cells through their peroxidase activity. We hypothesized that PRDX3 may inhibit autophagy to activate pyroptosis to induce growth of prostatic epithelial cells. Here we show that PRDX3 maintained the integrity of mitochondria and its depletion led to an enhancement of oxidative stresses. PRDX3-associated and PRDX3-free mitochondria co-existed in the same cells. PRDX3 expressed at higher levels in prostatic epithelial cells in prostate tissues from BPH patients and BPH-representative cell line than in prostate tissues from healthy donors and a cell line representing normal epithelial cells. PRDX3 suppressed autophagy flux and activated pyroptosis to induce inflammatory responses and stimulate the over-growth of prostate tissues. Therefore, higher levels of PDRX3 in prostatic epithelial cells may promote the initiation and development of BPH through autophagy inhibition and pyroptosis activation.

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

“…Peroxiredoxin 3 (PRDX3) is an oxidation/reduction-related protein found in the mitochondria, which has been found to exhibit protective antioxidant effects and inhibit autophagy ( 12 , 13 ). PRDX3 has been reported to promote cancer cell survival by aiding cancer cells to escape cell oxidation, and the protein expression levels of PRDX3 has been negatively associated with autophagy ( 12 , 14 ). Previously, PRDX3 has been identified as a target protein of miR-383, and a negative association between the expression levels of miR-383 and PRDX3 was found ( 15 ).…”

Dexmedetomidine Reduces the Lidocaine-Induced Neurotoxicity by Inhibiting Inflammasome Activation and Reducing Pyroptosis in Rats

“…The average TFL from three repeats was used for each test and the maximal heating time was 20 s to avoid tissue damage. 15) Terminal Deoxynucleotidyl Transferase-Mediated Deoxyuridine Triphosphate Nick-End Labeling (TUNEL) Staining Paraffin-embedded spinal cord tissue sections were prepared for TUNEL staining. After deparaffinization and rehydration, the tissue sections were treated with 3% H 2 O 2 for 10 min at room temperature, then digested with proteinase K with 1 : 200 dilution in Tris-buffered saline (TBS) for 30 min at 37 °C.…”

The Possibility and Molecular Mechanisms of Cell Pyroptosis After Cerebral Ischemia

“…Pyroptosis does not only occur during infectious diseases. Recent studies have shown that pyroptosis is also present in sterile inflammation, including diabetic atherosclerosis [23], acute liver injury [24], alcoholic hepatitis [25], diabetic cardiomyopathy [26], diabetic nephropathy [27], benign prostatic hyperplasia [28], Alzheimer's disease [29], temporal lobe epilepsy [30], renal ischemia/reperfusion [31], traumatic brain injury [32], ethanol-induced brain injury [33], and myocardial ischemia/reperfusion [34].…”