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Published on: May 26, 2023
Crocin protects PC12 cells against MPP(+)-induced injury through inhibition of mitochondrial dysfunction and ER
Guo-Feng Zhang1, Yi Zhang2, Gang Zhao1
1Department of Neurology, Chinese People's Liberation Army The Fourth Military Medical University First Affiliated Hospital, Xi'an, Shaanxi 710032, China.
Abstract:
The molecular machinery that mediates neuronal injury in neurodegenerative conditions such as Parkinson's disease (PD) remains to be fully deciphered, which will hopefully provide novel therapeutic targets for these disorders. Crocin, one of the water-soluble carotenoids isolated from the Crocus sativus L (saffron) stigma, has been reported to exert therapeutic potential in many disease models. Here, we establish an in vitro PD model using 1-methyl-4-phenylpyridinium (MPP(+))-injured PC12 cells to investigate the protective effects of crocin. Crocin treatment significantly attenuated MPP(+)-induced cell injury and apoptosis with little toxicity, and these protective effects were still observed even if crocin treatment was delayed to 6 h after injury. Crocin also inhibited MPP(+)-induced mitochondrial dysfunction, as evidenced by preservation of mitochondrial membrane potential (MMP) and ATP synthesis, which correlates with suppressed endoplasmic reticulum (ER) stress through inhibiting ER chaperone and ER related apoptotic factors. In addition, ER calcium release and morphological changes in ER lumen after MPP(+) exposure were all partially prevented by crocin. By using specific targeted small interfering RNA (siRNA) to knockdown the expression of the C/EBP homologous protein (CHOP), we found that crocin-induced protection and inhibition of ER stress was mediated by inverting MPP(+)-induced decrease of Wnt through the CHOP pathway. Our study demonstrates a pivotal role of ER stress in mediating PD related neuronal injury via the regulation of CHOP-Wnt pathway, and suggests the therapeutic values of crocin against ER stress-associated cytotoxicity.
Insights
Crocin, derived from saffron, protects against Parkinson
Area of Science:
- Neuroscience
- Molecular Biology
- Pharmacology
Background:
- Parkinson's disease (PD) neuronal injury mechanisms require further elucidation for novel therapeutic targets.
- Crocin, a carotenoid from saffron, shows therapeutic potential in various disease models.
- Understanding crocin's neuroprotective effects is crucial for developing new PD treatments.
Purpose of the Study:
- To investigate the protective effects of crocin against 1-methyl-4-phenylpyridinium (MPP(+))-induced neuronal injury in an in vitro Parkinson's disease model.
- To elucidate the molecular mechanisms underlying crocin's neuroprotection, focusing on endoplasmic reticulum (ER) stress and the CHOP-Wnt pathway.
Main Methods:
- Established an in vitro PD model using MPP(+)-injured PC12 cells.
- Administered crocin at various time points to assess its protective effects.
- Utilized small interfering RNA (siRNA) to knockdown C/EBP homologous protein (CHOP) expression to investigate pathway involvement.
Main Results:
- Crocin significantly attenuated MPP(+)-induced cell injury and apoptosis, even when treatment was delayed.
- Crocin preserved mitochondrial membrane potential (MMP) and ATP synthesis, suppressed ER stress, and inhibited ER-related apoptotic factors.
- Crocin's protective effects and ER stress inhibition were mediated by modulating the CHOP-Wnt pathway.
Conclusions:
- Endoplasmic reticulum (ER) stress plays a critical role in mediating PD-related neuronal injury via the CHOP-Wnt pathway.
- Crocin demonstrates significant therapeutic value against ER stress-associated cytotoxicity in a Parkinson's disease model.
- Crocin represents a promising therapeutic agent for Parkinson's disease and other neurodegenerative disorders involving ER stress.
