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Delayed Pulmonary Apoptosis of Diet-Induced Obesity Mice following Escherichia coli Infection through the Mitochondrial Apoptotic Pathway.

ABSTRACT: Escherichia coli (E. coli) is one of pathogens causing nosocomial pneumonia and could induce pulmonary excessive apoptosis. Although much has been learned about metabolic diseases induced by obesity, the information linking bacterial pneumonia to obesity is limited. Accordingly, we investigated the apoptosis of normal (lean) and diet-induced obesity (DIO, fed a high-fat diet) mice after nasal instillation with E. coli. Lung tissues were obtained at 0 (preinfection), 12, 24, and 72?h after infection, and acute pulmonary inflammation was observed at 12?h. Elevated cell apoptosis and percentage of pulmonary cells depolarized with collapse of the mitochondrial transmembrane potential (??m) occurred in response to bacterial infection. The relative mRNA and protein expressions of Bax, caspase-3, and caspase-9 increased, but Bcl-2 decreased in the lung. Interestingly, the apoptotic percentage and most of apoptosis-associated factors mentioned above peaked at 12 or 24?h in the lean-E. coli group, while at 24 or 72?h in the DIO-E. coli group. Taken together, these findings indicated that the E. coli pneumonia caused excessive pulmonary apoptosis through the mitochondria-mediated pathway, and the apoptosis was delayed in the DIO mice with E. coli pneumonia.

SUBMITTER: Wang F

PROVIDER: S-EPMC6854188 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Delayed Pulmonary Apoptosis of Diet-Induced Obesity Mice following Escherichia coli Infection through the Mitochondrial Apoptotic Pathway.

Wang Fengyuan F Zuo Zhicai Z Yang Zhuangzhi Z Chen Kejie K Fang Jing J Cui Hengmin H Shu Gang G Zhou Yi Y Geng Yi Y Ouyang Ping P

Oxidative medicine and cellular longevity 20191022

Escherichia coli (E. coli) is one of pathogens causing nosocomial pneumonia and could induce pulmonary excessive apoptosis. Although much has been learned about metabolic diseases induced by obesity, the information linking bacterial pneumonia to obesity is limited. Accordingly, we investigated the apoptosis of normal (lean) and diet-induced obesity (DIO, fed a high-fat diet) mice after nasal instillation with E. coli. Lung tissues were obtained at 0 (preinfection), 12, 24, ...[more]

PMID: 31772700

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Project description:In bacteria, SOS is a global response to DNA damage, mediated by the recA-lexA genes, resulting in cell cycle arrest, DNA repair, and mutagenesis. Previously, we reported that Escherichia coli responds to DNA damage via another recA-lexA-mediated pathway resulting in programmed cell death (PCD). We called it apoptosis-like death (ALD) because it is characterized by membrane depolarization and DNA fragmentation, which are hallmarks of eukaryotic mitochondrial apoptosis. Here, we show that ALD is an extreme SOS response that occurs only under conditions of severe DNA damage. Furthermore, we found that ALD is characterized by additional hallmarks of eukaryotic mitochondrial apoptosis, including (i) rRNA degradation by the endoribonuclease YbeY, (ii) upregulation of a unique set of genes that we called extensive-damage-induced (Edin) genes, (iii) a decrease in the activities of complexes I and II of the electron transport chain, and (iv) the formation of high levels of OH? through the Fenton reaction, eventually resulting in cell death. Our genetic and molecular studies on ALD provide additional insight for the evolution of mitochondria and the apoptotic pathway in eukaryotes. Importance: The SOS response is the first described and the most studied bacterial response to DNA damage. It is mediated by a set of two genes, recA-lexA, and it results in DNA repair and thereby in the survival of the bacterial culture. We have shown that Escherichia coli responds to DNA damage by an additional recA-lexA-mediated pathway resulting in an apoptosis-like death (ALD). Apoptosis is a mode of cell death that has previously been reported only in eukaryotes. We found that E. coli ALD is characterized by several hallmarks of eukaryotic mitochondrial apoptosis. Altogether, our results revealed that recA-lexA is a DNA damage response coordinator that permits two opposite responses: life, mediated by the SOS, and death, mediated by the ALD. The choice seems to be a function of the degree of DNA damage in the cell.

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Dataset Information

Delayed Pulmonary Apoptosis of Diet-Induced Obesity Mice following Escherichia coli Infection through the Mitochondrial Apoptotic Pathway.

Publications

Delayed Pulmonary Apoptosis of Diet-Induced Obesity Mice following <i>Escherichia coli</i> Infection through the Mitochondrial Apoptotic Pathway.

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