Neuroprotective effect of heat shock protein 60 on matrine-suppressed microglial activation

Zhang, Rui; Li, Yunhong; Hou, Xiaolin; Miao, Zhenhua; Wang, Yin

doi:10.3892/etm.2017.4691

Cited by 17 publications

(12 citation statements)

References 25 publications

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“…Therefore, to explore potential mechanisms underlying the decrease in the HSP60 intracellular levels in curcumin-treated cells, we evaluated possible extracellular release. Other groups and we have already shown that HSP60 can be secreted by cells, in particular by cancer cells via both secretion canonical pathways and via exosomes [15,23,24,26,50,[64][65][66][67]. In this work, we demonstrated that HSP60 is secreted by LAN-5 cells after 24 h of treatment with 25 µM of curcumin.…”

Section: Discussionsupporting

confidence: 63%

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Bavisotto

Gammazza

Cascio

et al. 2020

IJMS

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The fundamental challenge in fighting cancer is the development of protective agents able to interfere with the classical pathways of malignant transformation, such as extracellular matrix remodeling, epithelial–mesenchymal transition and, alteration of protein homeostasis. In the tumors of the brain, proteotoxic stress represents one of the main triggering agents for cell transformation. Curcumin is a natural compound with anti-inflammatory and anti-cancer properties with promising potential for the development of therapeutic drugs for the treatment of cancer as well as neurodegenerative diseases. Among the mediators of cancer development, HSP60 is a key factor for the maintenance of protein homeostasis and cell survival. High HSP60 levels were correlated, in particular, with cancer development and progression, and for this reason, we investigated the ability of curcumin to affect HSP60 expression, localization, and post-translational modifications using a neuroblastoma cell line. We have also looked at the ability of curcumin to interfere with the HSP60/HSP10 folding machinery. The cells were treated with 6, 12.5, and 25 µM of curcumin for 24 h, and the flow cytometry analysis showed that the compound induced apoptosis in a dose-dependent manner with a higher percentage of apoptotic cells at 25 µM. This dose of curcumin-induced a decrease in HSP60 protein levels and an upregulation of HSP60 mRNA expression. Moreover, 25 µM of curcumin reduced HSP60 ubiquitination and nitration, and the chaperonin levels were higher in the culture media compared with the untreated cells. Furthermore, curcumin at the same dose was able to favor HSP60 folding activity. The reduction of HSP60 levels, together with the increase in its folding activity and the secretion in the media led to the supposition that curcumin might interfere with cancer progression with a protective mechanism involving the chaperonin.

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Section: Discussionsupporting

confidence: 63%

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Bavisotto

Gammazza

Cascio

et al. 2020

IJMS

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“…Moreover, the extracellular release of Hsp60 increases the production of other pro-inflammatory factors through binding to toll-like receptor 4 (TLR-4) and stimulating neuronal cell death [ 55 ]. Over-activation of microglia in response to certain harmful factors, contributes to the progression of several neurodegenerative diseases, including AD [ 57 ]. Neurodegenerative diseases are associated with the secretion of various pro-inflammatory and cytotoxic factors by activated microglia in the brain [ 58 , 59 ].…”

Section: Hsp60mentioning

confidence: 99%

“…Neurodegenerative diseases are associated with the secretion of various pro-inflammatory and cytotoxic factors by activated microglia in the brain [ 58 , 59 ]. Therefore, inhibiting the activation of microglia and Hsp60 expression/release is an important strategy for the prevention of neurodegeneration [ 57 ]. Hsp60 levels were high in lymphocytes from AD patients when compared to controls [ 60 , 61 ].…”

Section: Hsp60mentioning

confidence: 99%

Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting

Campanella

Pace

Bavisotto

et al. 2018

IJMS

133

104

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Among diseases whose cure is still far from being discovered, Alzheimer’s disease (AD) has been recognized as a crucial medical and social problem. A major issue in AD research is represented by the complexity of involved biochemical pathways, including the nature of protein misfolding, which results in the production of toxic species. Considering the involvement of (mis)folding processes in AD aetiology, targeting molecular chaperones represents a promising therapeutic perspective. This review analyses the connection between AD and molecular chaperones, with particular attention toward the most important heat shock proteins (HSPs) as representative components of the human chaperome: Hsp60, Hsp70 and Hsp90. The role of these proteins in AD is highlighted from a biological point of view. Pharmacological targeting of such HSPs with inhibitors or regulators is also discussed.

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“…Interestingly, eHSPs, such as eHSP90, eHSP70, eHSP60, and eHSP27 might be highly expressed and released as "chaperokines", where they play a major role in inflammation and immunity [142,145,146]. However, dependent on the circumstances, the same HSP proteins are not as highly expressed and can be observed in lower amounts in the extracellular space, such as eHSP60 [147] and eHSP27 [148]. eHSPs can stimulate inflammatory cytokine release from immune cells [141,143], recruit Natural Killer (NK) cells [141], and activate microglial phagocytosis [70].…”

Section: Extracellular Hspsmentioning

confidence: 99%

Are Heat Shock Proteins an Important Link between Type 2 Diabetes and Alzheimer Disease?

Rowles

Keane

Heck

et al. 2020

IJMS

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Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.e., islet amyloid polypeptide; IAPP) and brain (β-Amyloid; Aβ). Both IAPP and Aβ can undergo misfolding and aggregation and accumulate in the extracellular space of their respective tissues of origin. As a main response to protein misfolding, there is evidence of the role of heat shock proteins (HSPs) in moderating T2D and AD. HSPs play a pivotal role in cell homeostasis by providing cytoprotection during acute and chronic metabolic stresses. In T2D and AD, intracellular HSP (iHSP) levels are reduced, potentially due to the ability of the cell to export HSPs to the extracellular space (eHSP). The increase in eHSPs can contribute to oxidative damage and is associated with various pro-inflammatory pathways in T2D and AD. Here, we review the role of HSP in moderating T2D and AD, as well as propose that these chaperone proteins are an important link in the relationship between T2D and AD.

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Neuroprotective effect of heat shock protein 60 on matrine-suppressed microglial activation

Cited by 17 publications

References 25 publications

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Curcumin Affects HSP60 Folding Activity and Levels in Neuroblastoma Cells

Heat Shock Proteins in Alzheimer’s Disease: Role and Targeting

Are Heat Shock Proteins an Important Link between Type 2 Diabetes and Alzheimer Disease?

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