Role Of Autophagy In Cells Research Articles

Functional suppression of Ripk1 blocks the NF-κB signaling pathway and induces neuron autophagy after traumatic brain injury.

Traumatic brain injury (TBI), known as intracranial injury, has been a serious threat to human health. Evidence exists indicating that autophagy and inflammatory responses contribute to secondary brain injury after TBI. Notably, receptor-interacting protein kinase 1 (Ripk1) exerts an important role in cell autophagy. Therefore, this study aims to explore the effect of Ripk1 on neuron autophagy and apoptosis in TBI. Initially, blood samples of patients with TBI and healthy persons were collected to detect the expression of Ripk1, nuclear factor-kappa B (NF-κB), and NF-kB inhibitor α (IKBα). Then rat models with TBI were successfully established and, respectively, treated with shRNA targeting Ripk1 (sh-Ripk1), Ripk1 overexpression plasmid (oe-Ripk1), or IKKα inhibitor (BAY 11-7082). Subsequently, reverse transcription quantitative polymerase chain reaction and Western blot analysis were conducted to detect the expression of Ripk1, IKBα, NF-κB signaling pathway-, and apoptosis-related factors. Enzyme-linked immunosorbent assay was used to detect the expression of inflammatory cytokines. Compared with healthy persons, the expression of Ripk1, NF-κB and IKBα in blood of TBI patients was significantly upregulated. After silencing of Ripk1 or inhibition of the NF-κB signaling pathway, the expression of IL-1β, IL-6, TNF-α, Bax, and cleaved-caspase-3 was downregulated, and the expression of Bcl-2, ATG5, and LC3II/LC3I was upregulated. Furthermore, neuron injury and apoptosis were notably reduced and neuron autophagy increased significantly by Ripk1 downregulation or IKKα inhibitor. Ripk1 overexpression contributed to activation of NF-κB signaling pathway, whereby aggravating TBI-induced damage. Silencing Ripk1 suppresses TBI by inhibiting inflammation and promoting autophagy of neurons via inhibition of NF-κB signaling pathway.

Autophagy Modulation as a Treatment of Amyloid Diseases.

Amyloids are fibrous proteins aggregated into toxic forms that are implicated in several chronic disorders. More than 30 diseases show deposition of fibrous amyloid proteins associated with cell loss and degeneration in the affected tissues. Evidence demonstrates that amyloid diseases result from protein aggregation or impaired amyloid clearance, but the connection between amyloid accumulation and tissue degeneration is not clear. Common examples of amyloid diseases are Alzheimer’s disease (AD), Parkinson’s disease (PD) and tauopathies, which are the most common forms of neurodegenerative diseases, as well as polyglutamine disorders and certain peripheral metabolic diseases. In these diseases, increased accumulation of toxic amyloid proteins is suspected to be one of the main causative factors in the disease pathogenesis. It is therefore important to more clearly understand how these toxic amyloid proteins accumulate as this will aide in the development of more effective preventive and therapeutic strategies. Protein homeostasis, or proteostasis, is maintained by multiple cellular pathways—including protein synthesis, quality control, and clearance—which are collectively responsible for preventing protein misfolding or aggregation. Modulating protein degradation is a very complex but attractive treatment strategy used to remove amyloid and improve cell survival. This review will focus on autophagy, an important clearance pathway of amyloid proteins, and strategies for using it as a potential therapeutic target for amyloid diseases. The physiological role of autophagy in cells, pathways for its modulation, its connection with apoptosis, cell models and caveats in developing autophagy as a treatment and as a biomarker is discussed.

The Role of Cell Autophagy in Toxicity Caused by Dental Nanomaterials

The Role of Cell Autophagy in Toxicity Caused by Dental Nanomaterials

Role of cell autophagy in peripheral nerve injury and regeneration

To review the mechanism and effects of cell autophagy in the pathophysiology changes of peripheral nerve injury. The recent literature about cell autophagy in peripheral nerve injury and regeneration was extensively reviewed and summarized. The researches through drugs intervention and gene knockout techniques have confirmed that the Schwann cell autophagy influences the myelin degeneration, debris clearance, inflammatory cells infiltration, and axon regeneration through JNK/c-Jun pathway. To adjust autophagy process could slow down the Wallerian degeneration, maintain the integrity of injured nerve, while the effect on axon regeneration is still controversial. The Schwann cell autophagy plays a key role in the pathophysiology changes of peripheral nerve injury, the further study of its mechanism could provide new methods for the therapy of peripheral nerve injury.

Beclin 1 promotes apoptosis and decreases invasion by upregulating the expression of ECRG4 in A549 human lung adenocarcinoma cells.

Although Beclin1 has been demonstrated to exert an important role in cell autophagy during carcinogenesis, its biological function in lung cancer has yet to be fully elucidated. A previous study by our laboratory identified that knockdown of Beclin1 promoted cell growth and inhibited apoptosis in the A549lung cancer cell line. In the present study, a Beclin1 lentiviral expression vector was constructed, and an A549cell line was established with a steady expression of Beclin1. Furthermore, the effect of Beclin1 overexpression on cell invasion and apoptosis, changes in the activities of the apoptosis‑associated caspases‑3 and ‑9, and the overexpression of esophageal cancer‑related gene4 (ECRG4) were examined. The results demonstrated that the overexpression of Beclin1 in A549cells reduced cell invasion by Matrigel invasion assay and promoted apoptosis by flow cytometric analysis (P<0.01) compared with Lenex‑packaged lentiviral particles and non‑transfected control groups. Furthermore, the overexpression of Beclin1 in A549cells increased the activities of caspases‑3 and ‑9 and the expression of ECRG4 (P<0.01) compared with Lenex‑packaged lentiviral particles and non‑transfected control groups. In conclusion, the overexpression of Beclin1 promoted apoptosis and decreased invasion by upregulating the expression of ECRG4 in A549lung adenocarcinoma cells. Therefore, the selection of Beclinl as a target for gene therapy represents a more effective method for the treatment of lung cancer.

Role of cell autophagy in invasion and metastasis of hepatocellular carcinoma

Role of cell autophagy in invasion and metastasis of hepatocellular carcinoma