Hyperbaric Oxygen Therapy Improves Parkinson's Disease by Promoting Mitochondrial Biogenesis via the SIRT-1/PGC-1α Pathway. Biomolecules Hyperbaric oxygen therapy (HBOT) has been suggested as a potential adjunctive therapy for Parkinson's disease (PD). PD is a neurodegenerative disease characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The aim of this study was to investigate the protective mechanisms of HBOT on neurons and motor function in a 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD and 1-methyl-4-phenylpyridinium (MPP)-mediated neurotoxicity in SH-SY5Y cells on the potential protective capability. In vivo: male C57BL/6 mice were randomly divided into three groups: control, MPTP group and MPTP+HBOT group. The MPTP-treated mice were intraperitoneally received MPTP (20 mg/kg) four times at 2 h intervals within a day. The day after MPTP treatment, MPTP+HBOT mice were exposed to hyperbaric oxygen at 2.5 atmosphere absolute (ATA) with 100% oxygen for 1 h once daily for 7 consecutive days. In vitro: retinoic acid (RA)-differentiated SH-SY5Y cells were treated with MPP for 1 h followed by hyperbaric oxygen at 2.5 ATA with 100% oxygen for 1 h. The results showed that MPTP induced a significant loss in tyrosine hydroxylase (TH)-positive neurons in the SNpc of mice. HBOT treatment significantly increased the number of TH-positive neurons, with enhanced neurotrophic factor BDNF, decreased apoptotic signaling and attenuated inflammatory mediators in the midbrain of MPTP-treated mice. In addition, MPTP treatment decreased the locomotor activity and grip strength of mice, and these effects were shown to improve after HBOT treatment. Furthermore, MPTP decreased mitochondrial biogenesis signaling (SIRT-1, PGC-1α and TFAM), as well as mitochondrial marker VDAC expression, while HBOT treatment was shown to upregulate protein expression. In cell experiments, MPP reduced neurite length, while HBOT treatment attenuated neurite retraction. Conclusions: the effects of HBOT in MPTP-treated mice might come from promoting mitochondrial biogenesis, decreasing apoptotic signaling and attenuating inflammatory mediators in the midbrain, suggesting its potential benefits in PD treatment. 10.3390/biom12050661

Peroxisome Proliferator-Activated Receptor and PGC-1 in Cancer: Dual Actions as Tumor Promoter and Suppressor. Yun Seong-Hoon,Han Sang-Heum,Park Joo-In PPAR research Peroxisome proliferator-activated receptor (PPAR) is part of a nuclear receptor superfamily that regulates gene expression involved in cell differentiation, proliferation, immune/inflammation response, and lipid metabolism. PPAR coactivator-1 (PGC-1), initially identified as a PPAR-interacting protein, is an important regulator of diverse metabolic pathways, such as oxidative metabolism and energy homeostasis. The role of PGC-1 in diabetes, neurodegeneration, and cardiovascular disease is particularly well known. PGC-1 is also now known to play important roles in cancer, independent of the role of PPAR in cancer. Though many researchers have studied the expression and clinical implications of PPAR and PGC-1 in cancer, there are still many controversies about the role of PPAR and PGC-1 in cancer. This review examines and summarizes some recent data on the role and action mechanisms of PPAR and PGC-1 in cancer, respectively, particularly the recent progress in understanding the role of PPAR in several cancers since our review was published in 2012. 10.1155/2018/6727421

Dexmedetomidine Exerts Renal Protective Effect by Regulating the PGC-1α/STAT1/IRF-1 Axis. Song Ying-Chun,Liu Ran,Li Ru-Hong,Xu Fei Nephron BACKGROUND:Ischemia-reperfusion (I/R) injury is the main cause of acute kidney injury (AKI), and its incidence and mortality increase year by year in the population. Dexmedetomidine (DEX) can improve AKI by regulating inflammation and oxidative stress, but its mechanism is still unclear. METHODS:A hypoxia/reoxygenation (H/R) model of HK-2 cells and a kidney I/R model of C57BL/6J mice were established. In the experiment, cells were transfected with sh-PGC-1α to inhibit PGC-1α expression. The changes of ROS level and mitochondrial membrane potential (MMP) were analyzed. HE staining was used to assess kidney damage in mice. Concentration of kidney injury markers serum creatinine and blood urea nitrogen and expression of inflammatory factors were detected by ELISA. qPCR analysis was used to detect mRNA levels of related proteins in cells and mouse kidney tissues. The protein intracellular content and phosphorylation levels were determined by Western blotting. RESULT:The production of inflammatory factors and ROS was increased in HK-2 cells treated with H/R, while MMP, cell viability, and mitochondrial-related protein levels were decreased. DEX attenuated pathological changes induced by H/R, while knockdown of PGC-1α eliminated the mitigation effect. DEX inhibited the damage of I/R to the kidneys of mice and increased the expression of mitochondrial-related proteins and PGC-1α in the kidneys, while inhibiting the phosphorylation of STAT1 and the expression of IRF-1. CONCLUSIONS:DEX appears to inhibit mitochondrial damage and cellular inflammation by upregulating PGC-1α to affect STAT1 phosphorylation level and IRF-1 expression, thereby preventing AKI. 10.1159/000514532

Peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) overexpression alleviates endoplasmic reticulum stress after acute kidney injury. Renal failure BACKGROUND:Mitochondrial biogenesis dysregulation and enhanced endoplasmic reticulum (ER) stress have been implicated in the progression of acute kidney injury (AKI). However, the interaction between these two events remains poorly understood. This study was designed to investigate the role of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) expression, a key factor in mitochondrial biogenesis, in renal ER stress at 24 h after AKI and the underlying mechanisms. METHODS:Mice were administered recombinant adenovirus encoding murine PGC-1α (100 μl, 1.0 × 10PFU/ml) or vehicle five days before renal ischemia reperfusion (I/R) or sham operation. Twenty-four hours after the operation, kidney and serum samples were collected for evaluation. RESULTS:We first confirmed that PGC-1α transfection elevated the PGC-1α levels and mitochondrial transcripts in the kidney 24 h after AKI. Then, we found PGC-1α overexpression improved renal function. PGC-1α transfection inhibited AKI-induced ER stress through the unfolded protein response (UPR) pathway, resulting in the suppression of apoptosis both mitochondrial and ER pathways. Further study showed that the expression of mitofusin 2 (Mfn2), an interaction protein between mitochondria and ER, was increased after PGC-1α overexpression. We also found the expression of a novel ER stress regulator, hairy and enhancer of split 1 (Hes1), was decreased after PGC-1α transfection. CONCLUSIONS:Our findings reveal that mitochondrial biogenesis plays an important role in the progression of AKI-induced ER stress and provide useful evidence for research on organelle crosstalk during AKI. 10.1080/0886022X.2022.2035764