Disturbance in calcium (Ca ) homeostasis has been involved in a variety of neuropathological conditions including Parkinson's disease (PD). The Ca channel, transient receptor potential channel 1 (TRPC1), plays a protective role in regulating entry of Ca activated by store depletion of Ca in endoplasmic reticulum (ER). We have showed that thioredoxin-1 (Trx-1) plays a role in suppressing ER stress in PD. However, whether Trx-1 regulates TRPC1 expression in PD is still unknown. In the present study, we demonstrated that treatment of 1-methyl-4-phenylpyridinum ion (MPP ) significantly reduced the expression of TRPC1 in PC12 cells, which was restored by Trx-1 overexpression, and further decreased significantly by Trx-1 siRNA. Moreover, we found that Ca entered into the cells was decreased by MPP in PC 12 cells, which was restored by Trx-1 overexpression, and further decreased by Trx-1 siRNA. MPP significantly increased calcium-dependent cysteine protease calpain1 expression in PC12 cells, which was suppressed by Trx-1 overexpression. Calpain1 expression was increased by Trx-1 siRNA or SKF96365, an inhibitor of TRPC1. Moreover, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) decreased TRPC1 expression in the substantia nigra pars compacta region (SNpc), which was restored in mice overexpressing Trx-1, and further decreased in mice of knockdown Trx-1. Inversely, the expression of calpain1 was increased by MPTP, which was suppressed in mice overexpressing Trx-1, and further increased in mice of knockdown Trx-1. In conclusion, Trx-1 regulates the Ca entry through regulating TRPC1 expression after treatment of MPP /MPTP.
Download full-text PDF |
Source |
---|---|
http://dx.doi.org/10.1111/ejn.15355 | DOI Listing |
Epigenomics
December 2024
Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, Pakistan.
Aim: The hypoxic tumor microenvironment (TME) in oral squamous cell carcinoma (OSCC) is primarily regulated by hypoxia-inducible factor-1 alpha (HIF-1α), impacting histone acetylation and methylation, which contribute to drug resistance. Vorinostat, a histone deacetylase inhibitor (HDACi), de-stabilizes HIF-1α, while PX-12, a thioredoxin-1 (Trx-1) inhibitor, prevents HIF-1α accumulation. Combining HDACi with a Trx-1 inhibitor may enhance efficacy and reduce resistance by increasing reactive oxygen species (ROS) in cancer cells.
View Article and Find Full Text PDFNan Fang Yi Ke Da Xue Xue Bao
September 2024
Department of Respiratory and Critical Care Medicine, First Affiliated Hospital of Bengbu Medical University, Bengbu Medical University, Bengbu 233000, China.
Objective: To investigate whether curcumin alleviates septic lung injury by inhibiting ferroptosis through modulating the TXNIP/TRX-1/GPX4 pathway.
Methods: Male C57BL/6 mice were randomly divided into Sham group, cecal ligation puncture (CLP)-induced sepsis group, CLP with curcumin treatment (50, 100, and 200 mg/kg) groups, and CLP with both curcumin (200 mg/kg) and TRX-1 inhibitor PX-12 (25 mg/kg) treatment group. Inflammatory factors, MDA, MPO, and GSH levels in the lung tissue of the mice were detected.
Basic Clin Pharmacol Toxicol
November 2024
Department of Pharmacology of Chinese Materia Medica, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
Ren Fail
December 2024
Department of Nephrology, Changshu Hospital affiliated to Nanjing University of Chinese Medicine, Changshu city, Jiangsu, China.
Redox Biol
September 2024
State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Department of Physiology, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, China. Electronic address:
Sepsis is a common complication of infections that significantly impacts the survival of critically patients. Currently, effective pharmacological treatment strategies are lacking. Auranofin, known as an inhibitor of Thioredoxin reductase (TrxR), exhibits anti-inflammatory activity, but its role in sepsis is not well understood.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!