Goudie 2017 Abstract IOC122

From Bioblast
Inhibition of mitochondrial fission as a novel treatment for IBD.

Link: Mitochondr Physiol Network 22.01

Goudie L, Mancini NL, Wang A, McKay DM, Shearer J (2017)

Event: IOC122

Inflammatory bowel disease (IBD) encompasses a group of disorders that involve an exaggerated immune response to intestinal microbes. Recently we, and others, have assessed the possibility that excessive mitochondrial fission affects epithelial-microbial interactions, decreases epithelial barrier function and contribute to enteric inflammation. Excessive fission, mediated by DRP1 and Fis1, promotes a remodeling of mitochondrial networks into more punctate mitochondria that generate more reactive oxygen species and can affect energy and cell death pathways. Hypothesising that elevated mitochondrial fission would occur in enteric inflammation, male Balb/c mice were given dextran sulfate sodium (DSS) (5% (w./v.) 5 days, 3 days water) or dinitrobenzene sulfonic acid (DNBS) (3 mg, intrarectally.) Β± an inhibitor of DRP1 and Fis1, P110 (3 mg/Kg, intraperitoneally.) daily. On necropsy DSS and DNBS displayed the characteristic signs of colitis associated with these models. Disease was substantially less in P110-treated mice as gauged by (i) macroscopic disease scores, (ii) shortening of the colon and (iii) colon motility (i.e. bead extrusion) (n=8-12). Analysis of histopathology on H&E stained sections of mid-colon revealed some improvement in P110 treated mice, but this was not a statistically significant result. Thus, systemic administration of a selective inhibitor of mitochondrial fission reduced the severity of disease in two different, commonly used murine models of colitis. Studies are required to define the mechanism of this effect in terms of the target cell (e.g. epithelium vs. macrophage) and systemic vs. local effects of the P110. We conclude that inhibition of DRP1 and Fis1 interaction provides a novel approach to mitigating IBD.

β€’ Bioblast editor: Kandolf G β€’ O2k-Network Lab: CA Calgary Shearer J

Labels: MiParea: mt-Structure;fission;fusion, Exercise physiology;nutrition;life style, mt-Medicine  Pathology: Other 

Organism: Mouse 


Goudie L(1), Mancini NL(2) Wang A(2), McKay DM(2), Shearer J(1,3)
  1. Dept Biomed Engineering, Schulich School Engineering
  2. Dept Physiol Pharmacol, Cumming School Medicine
  3. Fac Kinesiology
Univ Calgary, Canada. - [email protected]
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