Advances in the study of mitophagy-related receptor proteins / 生理学报

Cells selectively scavenge redundant or damaged mitochondria by mitophagy, which is an important mechanism of mitochondrial quality control. Recent studies have shown that mitophagy is mainly regulated by autophagy-related genes (Atgs) in yeast cells, while mitochondrial membrane associated proteins such as PTEN-induced putative kinase 1 (PINK1), NIX/BNIP3L, BNIP3, FUN14 domain containing 1 (FUNDC1), FKBP8/FKBP38, Bcl-2-like protein 13 (Bcl2L13), nucleotide binding domain and leucine-rich-repeat-containing proteins X1 (NLRX1), prohibitin 2 (PHB2) and lipids such as cardiolipin (CL) are the key mitophagic receptors in mammalian cells, which can selectively recognize damaged mitochondria, recruit them into isolation membranes by binding to microtubule-associated protein 1 light chain 3 (LC3) or γ-aminobutyric acid receptor-associated protein (GABARAP), and then fuse with lysosomes to eliminate the trapped mitochondria. This article reviews recent research progress of mitophagy-related receptor proteins.

Effect of low intensity photobiomodulation associated with norbixin-based poly (hydroxybutyrate) membrane on post-tenotomy tendon repair. In vivo study

Abstract Purpose: To evaluate the in vivo response of photobiomodulation therapy associated with norbixin-based poly(hydroxybutyrate) membrane (PHB) in tenotomized calcaneal tendon. Methods: Thirty rats were randomly allocated to six groups (n=5 each): LED groups (L1, L2 and L3) and membrane + LED groups (ML1, ML2 and ML3). The right calcaneal tendons of all animals were sectioned transversely and were irradiated with LED daily, one hour after surgery every 24 hours, until the day of euthanasia. At the end of the experiments the tendons were removed for histological analysis. Results: The histological analysis showed a significant reduction in inflammatory cells in the ML1, ML2 and ML3 groups (p=0.0056, p=0.0018 and p<0.0001, respectively) compared to those in the LED group. There was greater proliferation of fibroblasts in the ML1 (p<0.0001) and L3 (p<0.0001) groups. A higher concentration of type I collagen was also observed in the ML1 group (p=0.0043) replacing type III collagen. Conclusion: Photobiomodulation in association with norbixin-based PHB membrane led to control of the inflammatory process. However, it did not favor fibroblast proliferation and did not optimize type I collagen formation in the expected stage of the repair process.

Characterization and assessment of the genotoxicity and biocompatibility of poly (hydroxybutyrate) and norbixin membranes

Abstract Purpose To synthesize and characterize poly(hydroxybutyrate) (PHB) and norbixin membranes to evaluate them for genotoxicity in rats and wound healing in mice by histological staining. Methods For the evaluation of genotoxicity, male rats ( Rattus novegicus ) were divided into three groups (n= 5): 5% PHB/Norbixin membrane introduced into the peritoneum by laparotomy; B - negative control; C - positive control (intraperitoneal dose of cyclophosphamide 50 mg/kg). For the evaluation of biocompatibilty, a cutaneous wound was induced on the back of males mice ( Mus musculus ) divided into two experimental treatment groups: control and membrane that underwent euthanasia after 7 and 14 days treatment. Statistical analysis ware made by One Way Anova post hoc Tukey Test (p<0.05). Results Regarding the incidence of polychromatic erythrocytes, there was no difference between negative control and 5% PHB/Norbixin membrane; however, when compared to the positive control represented by cyclophosphamide, there was a significant difference (p <0.001). As for DNA damage, the changes induced in the first 4h were repaired in 24h. In addition, the membrane was effective in abbreviating the inflammatory process and served as a scaffold due to the stimulus to reepithelialization mainly on the 7 days of treatment. Conclusion The non-genotoxic PHB/Norbixin 5% membrane presented promising results that suggest its effectiveness as a guide for tissue regeneration given its biocompatibility.

The novel long noncoding RNA LOC283070 is involved in the transition of LNCaP cells into androgen-independent cells via its interaction with PHB2 / 亚洲男科学杂志(英文版)

We sought to investigate the underlying mechanism of action of the long noncoding RNA (lncRNA) LOC283070 in the development of androgen independence in prostate cancer. The interactions between LOC283070 and target proteins were investigated by RNA pull-down and RNA-binding protein immunoprecipitation (RIP) assays. Subcellular fractionation and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the subcellular localization of LOC283070. Western blotting was performed to detect the expression of prohibitin 2 (PHB2). Luciferase activity assays were performed to evaluate the effects of LOC283070 and PHB2 on the androgen receptor (AR) signaling pathway. A methyl thiazolyl tetrazolium (MTT) assay and a growth curve assay were used to test cell viability. Flow cytometry was performed to analyze cell cycles. A transwell assay was employed to test cell migration. We identified PHB2 as an interaction partner of LOC283070 in the pull-down and RIP experiments. Furthermore, we confirmed that the enrichment of LOC283070 with PHB2 in androgen-independent LNCaP (LNCaP-AI) cells was much greater than that in LNCaP cells. Moreover, the expression of PHB2 was not significantly different between the two cell lines, and the expression of LOC283070 in the nuclei of the LNCaP-AI cells was significantly greater than that in the LNCaP cells. In vitro data revealed that PHB2 overexpression significantly inhibited AR activity and cell proliferation and migration and induced accumulation of prostate cancer cells in G0/G1 phase. Moreover, the overexpression of LOC283070 fully abrogated the effects of PHB2 overexpression. In conclusion, we found that LOC283070 can bind to PHB2 located in the nucleus and inhibit its effect, and this is one of the mechanisms by which LOC283070 is involved in the transition of LNCaP cells into androgen-independent cells.