Bcl-2 Protein Interplay on the Outer Mitochondrial Membrane

Edlich, Frank; Martinou, Jean‐Claude

doi:10.1007/978-1-4939-3612-0_4

Cited by 9 publications

(6 citation statements)

References 105 publications

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“…In fact, both the extrinsic and intrinsic apoptotic pathways may be involved in caspase-3 cleavage [ 63 ], but Bcl-2 is implicated only in the intrinsic pathways. Bcl-2 blocks the release of cytochrome c from the mitochondria into the cytosol [ 64 ], inhibiting changes in mitochondrial membrane potential and mitochondrial permeability [ 65 ].…”

Section: Discussionmentioning

confidence: 99%

Future in the Past: Azorella glabra Wedd. as a Source of New Natural Compounds with Antiproliferative and Cytotoxic Activity on Multiple Myeloma Cells

Lamorte

Faraone

Laurenzana

et al. 2018

IJMS

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Multiple myeloma (MM) is the second most common hematologic malignancy and, although the development of novel agents has improved survival of patients, to date, it remains incurable. Thus, newer and more effective therapeutic strategies against this malignancy are necessary. Plant extracts play an important role in anti-tumor drug discovery. For this reason, in the investigation of novel natural anti-MM agents, we evaluated the phytochemical profiles, in vitro antioxidant activity, and effects on MM cells of Azorella glabra (AG) Wedd. Total polyphenols (TPC), flavonoids (TFC), and terpenoids (TTeC) contents were different among samples and the richest fractions in polyphenols demonstrated a higher antioxidant activity in in vitro assays. Some fractions showed a dose and time dependent anti-proliferative activity on MM cells. The chloroform fraction (CHCl3) showed major effects in terms of reduction of cell viability, induction of apoptosis, and cell cycle arrest on MM cells. The apoptosis induction was also confirmed by the activation of caspase-3. Importantly, the CHCl3 fraction exhibited a negligible effect on the viability of healthy cells. These results encourage further investigations on AG extracts to identify specific bioactive compounds and to define their potential applications in MM.

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Section: Discussionmentioning

confidence: 99%

Future in the Past: Azorella glabra Wedd. as a Source of New Natural Compounds with Antiproliferative and Cytotoxic Activity on Multiple Myeloma Cells

Lamorte

Faraone

Laurenzana

et al. 2018

IJMS

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show abstract

“…Apoptosis is a process of programmed cell death that occurs through the regulation of genes, activation of extracellular molecules and external factors ( 16 ). Bcl-2, as one of the cytokines with anti-apoptotic function, can inhibit free radicals to induce intracellular calcium overload, causing blocked mitochondrial membrane permeability and caspase activation, thereby inhibiting apoptosis ( 17 ). Bax is a class of genes that can promote apoptosis through the regulation of cytokine, and studies have shown that the ratio of Bax/Bcl-2 can directly reflect cell apoptosis ( 18 ).…”

Section: Discussionmentioning

confidence: 99%

Therapeutic effect of berberine on renal ischemia-reperfusion injury in rats and its effect on Bax and Bcl-2

Hai-ya

Lei

2018

Exp Ther Med

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This study aimed to investigate the therapeutic effect of berberine on renal ischemia-reperfusion injury in rats and its effect on Bax and Bcl-2. Sixty adult SD rats were randomly divided into four groups: control group A, renal ischemia-reperfusion group B, berberine group C and berberine + exendin-(9–39) treatment group D. In group A, right kidney was resected and left renal pedicle was separated, but left renal artery was not blocked. Renal ischemia-reperfusion model was established in other groups. Rats in group C were not subjected to any treatment after model construction. Rats in group C and D were subjected to intraperitoneal injection of berberine 7 days before the experiment. Besides that, intraperitoneal injection of exendin-(9–39) was performed at day 1 and 4 after model construction. Automatic biochemical analyzer was used to measure serum creatinine (SCr) and blood urea nitrogen (BUN). Malondialdehyde (MDA) in renal cortex was measured by enzyme-linked immunosorbent assay and contents of Bax and Bcl-2 in renal tissue were measured by western blot analysis. Apoptosis of rat renal cells was detected by TUNEL assay. The results showed that levels of SCr, BUN, MDA and Bax were significantly higher in group B than in other groups (P<0.05). Levels of Bcl-2 in group B were significantly higher than those in group A but significantly lower than those in group C and D. Compared with group A, apoptosis of renal cells was more severe in group B. Compared with group B, apoptosis of renal cells was significantly improved in group C and D, but was still more severe than that in group A. In conclusion, berberine can effectively improve renal function in rats with renal ischemia-reperfusion injury by inhibiting Bax expression and promoting Bcl-2 expression.

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“…Bax is a mitochondrial pro-apoptotic protein, the expression of which increases during the activation of the intrinsic apoptotic pathway and leads to mitochondrial injury (51). At the same time, Bcl2 is an anti-apoptotic protein which is produced in order to counteract pro-apoptotic signals and protect from mitochondrial injuries (52). The Bax/Bcl2 ratio is considered a measure of cell susceptibility to apoptosis (53) and in the current study, this ratio was found to be significantly decreased following MS administration in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Magnesium sulfate ameliorates carbon monoxide‑induced cerebral injury in male rats

et al. 2018

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Carbon monoxide (CO) has been shown to induce several cardiovascular abnormalities, as well as necrosis, apoptosis and oxidative stress in the brain. Magnesium sulfate (MS) has been shown to have beneficial activities against hypoxia in the brain. In the present study, the possible protective effects of MS against CO-induced cerebral ischemia were investigated. For this purpose, 25 male Wistar rats were exposed to 3,000 ppm CO for 1 h. The animals were divided into 5 groups (n=5 in each group) as follows: The negative control group (not exposed to CO), the positive control group (CO exposed and treated with normal saline), and 3 groups of CO-exposed rats treated with MS (75, 150 and 300 mg/kg/day) administered intraperitoneally for 5 consecutive days. On the 5th day, the animals were sacrificed and the brains were harvested for the evaluation of necrosis, apoptosis and oxidative stress. Histopathological evaluation revealed that MS reduced the number and intensity of necrotic insults. The Bax/Bcl2 ratio and malondialdehyde (MDA) levels were significantly decreased in a dose-dependent manner in the MS-treated rats compared to the positive control group, while a significant dose-dependent increase in Akt expression, a pro-survival protein, was observed. In addition, MS administration reduced pro-apoptotic indice levels, ameliorated histological insults, favorably modulated oxidative status and increased Akt expression levels, indicating a possible neuroprotective effect in the case of CO poisoning. On the whole, the findings of this study indicate that MS may prove to be useful in protecting against CO-induced cerebral injury.

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Bcl-2 Protein Interplay on the Outer Mitochondrial Membrane

Cited by 9 publications

References 105 publications

Future in the Past: Azorella glabra Wedd. as a Source of New Natural Compounds with Antiproliferative and Cytotoxic Activity on Multiple Myeloma Cells

Future in the Past: Azorella glabra Wedd. as a Source of New Natural Compounds with Antiproliferative and Cytotoxic Activity on Multiple Myeloma Cells

Therapeutic effect of berberine on renal ischemia-reperfusion injury in rats and its effect on Bax and Bcl-2

Magnesium sulfate ameliorates carbon monoxide‑induced cerebral injury in male rats

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