Mitochondrial DNA damage and a hypoxic response are induced by CoCl2 in rat neuronal PC12 cells

Wang, Guichun; Hazra, Tapas K.; Mitra, Sankar; Lee, Heung Man; Englander, Ella W.

doi:10.1093/nar/28.10.2135

Cited by 156 publications

(118 citation statements)

References 51 publications

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“…Hypoxia-induced Cell Lysis Measurements-The method to induce chemical hypoxia was adapted from Wang et al (37). A stock solution of cobalt chloride was made in sterile double distilled water and various concentrations (25 M to 2 mM) were used for a 2-h treatment to induce hypoxia in Jurkat cells.…”

Section: Methodsmentioning

confidence: 99%

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Hsp90 Inhibition Accelerates Cell Lysis

Sreedhar¹,

Kálmán²,

Pato³

et al. 2003

Journal of Biological Chemistry

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The 90 kDa heat shock protein, Hsp90, is an abundant molecular chaperone participating in the cytoprotection of eukaryotic cells. Here we analyzed the involvement of Hsp90 in the maintenance of cellular integrity using partial cell lysis as a measure. Inhibition of Hsp90 by geldanamycin, radicicol, cisplatin, and novobiocin induced a significant acceleration of detergent-and hypotonic shock-induced cell lysis. The concentration and time dependence of cell lysis acceleration was in agreement with the Hsp90 inhibition characteristics of the N-terminal inhibitors, geldanamycin and radicicol. Glutathione and other reducing agents partially blocked geldanamycin-induced acceleration of cell lysis but were largely ineffective with other inhibitors. Indeed, geldanamycin treatment led to superoxide production and a change in membrane fluidity. When Hsp90 content was diminished using anti-Hsp90 hammerhead ribozymes, an accelerated cell lysis was also observed. Hsp90 inhibition-induced cell lysis was more pronounced in eukaryotic (yeast, mouse red blood, and human T-lymphoma) cells than in bacteria. Our results indicate that besides the geldanamycin-induced superoxide production, and a consequent increase in cell lysis, inhibition or lack of Hsp90 alone can also compromise cellular integrity. Moreover, cell lysis after hypoxia and complement attack was also enhanced by any type of Hsp90 inhibition used, which shows that the maintenance of cellular integrity by Hsp90 is important in physiologically relevant lytic conditions of tumor cells.The 90 kDa heat shock protein (Hsp90) 1 is a central part of a chaperone meshwork chaperoning a large number of substrate proteins (1-5). Besides being a partner of a large number of co-chaperones and substrates, Hsp90 binds to filamentous actin and tubulin (6 -8) and the involvement of the cytoskeleton in the traffic of Hsp90 substrates has also been demonstrated (5, 9). Together with other chaperones, like Hsp27 and Hsp70, Hsp90 is involved in cytoprotection (10 -12).Cell lysis is one of the most commonly used methods to test cellular integrity. Moreover, lysis rate anomalies (13,14) together with diffusional anomalies (15, 16) were used as important arguments for the organization of the cytoplasm. Since cellular integrity is preserved after a partial cell lysis to a large extent (13,14), partial lysis provides a highly sensitized, but still somewhat organized cellular system, where the contribution of various components to both the cytoplasmic organization and cellular stability can be studied.The original aim of the present study was to examine whether Hsp90 inhibition induces any change in the rate of cell lysis induced by mild detergent treatment or hypotonic shock. The rationale behind these experiments was to test, whether Hsp90, a cytoprotective chaperone, binding to "thousand-andone" substrates and other proteins is involved in the maintenance of cellular integrity (17), and whether its inhibition renders cells more "lysis-prone." The first experiments were very promising: geldan...

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Section: Methodsmentioning

confidence: 99%

“…Hypoxia was induced using cobalt chloride (37). Geldanamycin and radicicol both caused a significant increase of hypoxia-induced cell lysis in Jurkat cells.…”

Section: Geldanamycin-induced Lysis Acceleration In Bacterial Andmentioning

confidence: 99%

Hsp90 Inhibition Accelerates Cell Lysis

Sreedhar¹,

Kálmán²,

Pato³

et al. 2003

Journal of Biological Chemistry

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“…CoCl 2 has been widely used as a hypoxia-mimicking agent in mammalian systems (104)(105)(106)(107)(108), but the mechanisms by which it induces hypoxia-mimicking responses are not fully understood. However, Sre1p is required for adaptation to CoCl 2 in C. neoformans.…”

Section: Fungi With Srebp Orthologsmentioning

confidence: 99%

Regulation of hypoxia adaptation: an overlooked virulence attribute of pathogenic fungi?

Grahl¹,

Cramer²

2009

Med. Mycology

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SummaryOver the past two decades, the incidence of fungal infections has dramatically increased. This is primarily due to increases in the population of immunocompromised individuals attributed to HIV/ AIDS pandemic and immunosuppression therapies associated with organ transplantation, cancer, and other diseases where new immunomodulatory therapies are utilized. Significant advances have been made in understanding how fungi cause disease, but clearly much remains to be learned about the pathophysiology of these often lethal infections.Fungal pathogens face numerous environmental challenges as they colonize and infect mammalian hosts. Regardless of a pathogen's complexity, its ability to adapt to environmental changes is critical for its survival and ability to cause disease. For example, at sites of fungal infections, the significant influx of immune effector cells and the necrosis of tissue by the invading pathogen generate hypoxic microenvironments to which both the pathogen and host cells must adapt in order to survive. However, our current knowledge of how pathogenic fungi adapt to and survive in hypoxic conditions during fungal pathogenesis is limited. Recent studies have begun to observe that the ability to adapt to various levels of hypoxia is an important component of the virulence arsenal of pathogenic fungi. In this review, we focus on known oxygen sensing mechanisms that non-pathogenic and pathogenic fungi utilize to adapt to hypoxic microenvironments and their possible relation to fungal virulence.

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“…It has been reported that chemical hypoxia=reoxy-genation was simulated by the addition and the removal of chemicals such as NaN 3 or CoCl 2 or Na 2 S 2 O 4 (Rose et al, 1998;Wang et al, 2000;Zhang et al, 2005). The neurons are extremely sensitive to hypoxia and reoxygenation insult (Faroqui et al, 1994).…”

Section: Cell Toxicity Induced By Na 2 S 2 Omentioning

confidence: 99%

Protective Effects of Salidroside on Hypoxia/Reoxygenation Injury by Sodium Hydrosulfite in PC12 Cells

Chen

Lü

Wang

et al. 2007

Pharmaceutical Biology

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Hypoxia=reoxygenation causes cellular injury and death associated with many pathophysiologic conditions, including respiratory disorders, myocardial ischemia, and tumour progression diseases. Neuronal pheochromocytoma (PC12) cells are widely used as a model system for neurologic research and are subject to chemical hypoxia induced with sodium hydrosulfite (Na 2 S 2 O 4 ), a common oxygen-consuming agent. Salidroside, which is the main active component of the famous traditional Chinese herb Rhodiola rosea L. (Crassulaceae), has been proved to possess many bioactivities. In this article, we studied the protective effects of salidroside on hypoxia= reoxygenation injury in PC12 cells induced by Na 2 S 2 O 4 . Cultures of PC12 cells were exposed for 1 h to 10 mM Na 2 S 2 O 4 for hypoxia, followed by reoxygenation for 2 h. The results showed that salidroside was very stable in medium and was not harmful to PC12 cells at the experimental concentrations of 0 $ 200 mg=mL. The cytoprotection by salidroside was dose-dependent, and the cell viability was 41.8 AE 5.7%, 62.4 AE 4.1%, and 92.2 AE 3.7% at 0, 50, and 100 mg=mL of salidroside, respectively. The level of released LDH significantly decreased from 513.5 AE 5.5% (without salidroside) to 258.1 AE 6.3% (with 100 mg=mL salidroside). Flow cytometry was performed to measure apoptotic rate. The results of flow cytometry assay indicated that the apoptotic rate was 17.0 AE 1.2% after hypoxia=reoxygenation injury. When the cells were treated with salidroside 12.5, 50 and 100 mg=mL, the apoptotic rate was 9.5 AE 0.9%, 7.4 AE 0.5%, and 4.5 AE 0.4%, respectively. In addition, our results were confirmed by inspection of cell morphology of PC12 cells. Treatment with salidroside (12.5, 50, 100 mg=mL) significantly prevented the cells from morphologic changes. All the above results showed salidroside could effectively protect PC12 cell against hypoxia=reoxygenation injury.

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Mitochondrial DNA damage and a hypoxic response are induced by CoCl2 in rat neuronal PC12 cells

Cited by 156 publications

References 51 publications

Hsp90 Inhibition Accelerates Cell Lysis

Hsp90 Inhibition Accelerates Cell Lysis

Regulation of hypoxia adaptation: an overlooked virulence attribute of pathogenic fungi?

Protective Effects of Salidroside on Hypoxia/Reoxygenation Injury by Sodium Hydrosulfite in PC12 Cells

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