Mitochondrial heat shock protein mortalin as potential target for therapies based on oxidative stress

Pagliarone, Ana Carolina; Castañeda, Edwin David; Santana, Jhonne Pedro Pedott; Oliveira, Caio Almeida Batista de; Robeldo, Thaiane; Teixeira, Felipe Roberti; Borra, Ricardo Carneiro

doi:10.1016/j.pdpdt.2021.102256

Cited by 6 publications

(8 citation statements)

References 44 publications

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“…Therefore, it is a feasible assumption that HSP inhibitors can be added during PDT to minimize this inefficiency. This assumption has currently been demonstrated in several cancer-related studies ( 34 , 35 ); however, no evidence on the combined administration of PDT and HSP inhibitors exists in the context of the antibacterial field.…”

Section: Introductionmentioning

confidence: 98%

Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo

Zhang

Liu

et al. 2023

mSphere

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Section: Introductionmentioning

confidence: 98%

Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo

Zhang

Liu

et al. 2023

mSphere

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“…If upregulation of mitochondrial mass would be a central defense mechanism to handle rising proteotoxic stress, induction of HspA9 could also be explained by increased translocation of proteins into the mitochondrial matrix during mitochondrial biogenesis, as it is the central subunit of the PAM (presequence translocase-associated motor) (50). Also, HspA9 could mirror the need for increased oxidative stress defense, as it has been described to play a key role in tumor survival especially under oxidative stress (51). HspA9 has been shown to mediate hypoxia induced preconditioning by preserving the activity of Cox1 and hence decreasing mitochondrial reactive oxygen species (ROS) production (52).…”

Section: Discussionmentioning

confidence: 99%

“…to play a key role in tumor survival especially under oxidative stress (51). HspA9 has been shown to mediate hypoxia induced preconditioning by preserving the activity of Cox1 and hence decreasing mitochondrial reactive oxygen species (ROS) production (52).…”

Section: Discussionmentioning

confidence: 99%

Induction of mitochondrial heat shock proteins and mitochondrial biogenesis in endothelial cells upon acute methylglyoxal stress: Evidence for hormetic autofeedback

Bulkescher

Fleming

Rodemer

et al. 2021

Preprint

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Increased metabolic flux produces potentially harmful side-products, such as reactive dicarbonyl and oxygen species. The reactive dicarbonly methylglyoxal (MG) can impair oxidative capacity, which is downregulated in type 2 diabetes. Heat shock proteins (HSPs) of subfamily A (Hsp70s) promote ATP-dependent processing of damaged proteins during MG exposure which also involve mitochondrial proteins. Since the protection of mitochondrial proteins could promote higher production of reactive metabolites due to increased substrate flux, tight regulation of HspA-mediated protein handling is important. We hypothesized that stress-inducible HspAs (HspA1A/HspA1B) are pivotal for maintaining mitochondrial biogenesis during acute MG-stress. To analyze the role of stress-inducible HspA1A/HspA1B for maintenance of mitochondrial homeostasis during acute MG exposure, we knocked out HSPA1A/HSPA1B in mouse endothelial cells. HSPA1A/HSPA1B KO cells showed upregulation of the mitochondrial chaperones HspA9 (mitochondrial Hsp70/mortalin) and HspD1 (Hsp60) as well as induction of mitochondrial biogenesis upon MG exposure. Increased mitochondrial biogenesis was reflected by elevated mitochondrial branching, total count and area as well as by upregulation of mitochondrial proteins and corresponding transcription factors. Our findings suggest that mitochondrial HspA9 and HspD1 promote mitochondrial biogenesis during acute MG stress, which is counterregulated by HspA1A/HspA1B to prevent mitochondrial overstimulation and to maintain balanced oxidative capacity under metabolic stress conditions. These data support an important role of HSPs in MG-induced hormesis.

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“…Heat shock proteins act as chaperones at the molecular level and have been investigated in numerous diseases associated with oxidative stress, including obesity ( 8 , 9 ). A specific subfamily of heat-shock proteins are the HSPB family of molecular chaperones, which comprises ten members (HSPB1-10, also called small HSP) ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Heat shock protein B7 (HSPB7) inhibits lung adenocarcinoma progression by inhibiting glycolysis

Chen,

Li,

Shen

et al. 2023

Oncol Rep

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In the present study, it was aimed to investigate the effects and potential mechanisms of heat shock protein B7 (HSPB7) on lung adenocarcinoma (LUAD). Bioinformatic analysis was performed to explore the association between HSPB7 expression and patients with LUAD. MTT, colony formation, wound healing and Transwell assays were performed to examine the proliferative, migratory and invasive abilities of H1975 and A549 cells. Western blot analysis was conducted to determine the corresponding protein expression. Co-Immunoprecipitation and Chromatin immunoprecipitation assays were carried out to reveal the interaction between HSPB7 and myelodysplastic syndrome 1 and ecotropic viral integration site 1 complex locus (MECOM). In addition, an animal model was conducted by the subcutaneous injection of A549 cells into BALB/c nude mice, and tumor weight and size were measured. HSPB7 was downregulated in LUAD tissues and cells, and its expression level correlated with patient prognosis. Cell functional data revealed that silencing of HSPB7 promoted lung cancer cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT); whereas overexpression of HSPB7 led to the opposite results. Furthermore, bioinformatics analysis showed that HSPB7 inhibited glycolysis. HSPB7 decreased glucose consumption, lactic acid production, and lactate dehydrogenase A, hexokinase 2 and pyruvate kinase muscle isoform 2 protein levels. The results demonstrated that MECOM was a transcription factor of HSPB7. Collectively, these results suggested that HSPB7 is regulated by MECOM, and that HSPB7 attenuates LUAD cell proliferation, migration, invasion and EMT by inhibiting glycolysis.

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Mitochondrial heat shock protein mortalin as potential target for therapies based on oxidative stress

Cited by 6 publications

References 44 publications

Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo

Heat Shock Protein Inhibitors Show Synergistic Antibacterial Effects with Photodynamic Therapy on Caries-Related Streptococci In Vitro and In Vivo

Induction of mitochondrial heat shock proteins and mitochondrial biogenesis in endothelial cells upon acute methylglyoxal stress: Evidence for hormetic autofeedback

Heat shock protein B7 (HSPB7) inhibits lung adenocarcinoma progression by inhibiting glycolysis

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