PMID- 38466070
OWN - NLM
STAT- Publisher
LR  - 20240311
IS  - 1078-6791 (Print)
IS  - 1078-6791 (Linking)
DP  - 2024 Mar 8
TI  - Inhibition of Ca2+ induced Macrophage Oxidative Stress Cascade in Mice With 
      Ulcerative Colitis.
LID - AT10508 [pii]
AB  - CONTEXT: In the context of ulcerative coloproctitis (UC), a chronic and 
      non-specific inflammatory condition of the colon and rectum with an elusive 
      etiology, the therapeutic potential of G protein-coupled receptor 109a (GPR109a) 
      has gained prominence. GPR109a is expressed in various cell types including 
      colonic epithelium, adipocytes, neutrophils, and macrophages, positioning it as a 
      promising candidate for pharmacological intervention in colitis. OBJECTIVE: the 
      mechanistic role of GPR109a in a mouse model of UC and to assess its capacity to 
      mitigate the disease's progression. DESIGN: The research team performed an animal 
      study. SETTING: Conducted by a research team in the biomedical setting of the 
      People's Hospital of Dongxihu District in Wuhan, Hubei province of China. 
      ANIMALS: This animal study engaged 16 specific pathogen-free (SPF) male BALB/c 
      mice, aged between 4 to 6 weeks and weighing 20-24 grams each. OUTCOME MEASURES: 
      (1) analysis of rectal lesions via hematoxylin-eosin (HE) staining, (2) the use 
      of transmission electron microscopy to examine suborganelle spatial 
      relationships, (3) Western blot analysis to evaluate a spectrum of protein 
      expressions such as phosphorylated IP3R, p-PERK, p-IRE-1alpha, mitofusins, NADPH 
      oxidases, TNF-alpha, and IL-1beta, and (4) determination of intracellular calcium 
      concentrations to gauge intestinal barrier function impairment involving specific 
      calcium pathway signals. RESULTS: Results from the study painted a picture of 
      significant infiltration by inflammatory cells within the mucosal and submucosal 
      layers, compounded by pronounced endoplasmic reticulum expansion. Abundant 
      interfaces between the ER and the mitochondria formed multiple structures known 
      as mitochondria-associated membranes or MAMs. When evaluated under calcium-rich 
      conditions, the protein levels mentioned earlier were notably elevated in the 
      GPR109a knockdown (KD) group versus the infection control (NC) counterparts. 
      However, this differential expression disappeared under calcium-depleted 
      conditions or when treated with 2-aminoethyl diphenyl borinate (2-APB). 
      Additionally, fluorescence intensity assays showed marked suppression in the 
      GPR109a-KD plus lipopolysaccharide (LPS) group compared to the control. 
      CONCLUSIONS: Drawing these observations to a close, the study concluded that 
      GPR109a has an inhibitory effect on the advancement of ulcerative coloproctitis 
      in mice. This is mediated through the activation of a calcium-induced oxidative 
      stress cascade within macrophages, delineating a promising therapeutic pathway 
      for the management of this inflammatory disease.
FAU - Yan, Hao
AU  - Yan H
FAU - Li, Guohong
AU  - Li G
LA  - eng
PT  - Journal Article
DEP - 20240308
PL  - United States
TA  - Altern Ther Health Med
JT  - Alternative therapies in health and medicine
JID - 9502013
SB  - IM
EDAT- 2024/03/11 12:43
MHDA- 2024/03/11 12:43
CRDT- 2024/03/11 09:44
PHST- 2024/03/11 12:43 [medline]
PHST- 2024/03/11 12:43 [pubmed]
PHST- 2024/03/11 09:44 [entrez]
AID - AT10508 [pii]
PST - aheadofprint
SO  - Altern Ther Health Med. 2024 Mar 8:AT10508.