Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0020538 (
hypertension
)
170,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Accumulating studies have argued that the mitochondrial unfolded protein response (UPR
mt
) is a mitochondrial stress response that promotes longevity in model organisms. In the present study, we screened an off-patent drug library to identify compounds that activate UPR
mt
using a mitochondrial chaperone hsp-6::GFP reporter system in Caenorhabditis elegans.
Metolazone
, a diuretic primarily used to treat congestive heart failure and
high blood pressure
, was identified as a prominent hit as it upregulated hsp-6::GFP and not the endoplasmic reticulum chaperone hsp-4::GFP. Furthermore, metolazone specifically induced the expression of mitochondrial chaperones in the HeLa cell line.
Metolazone
also extended the lifespan of worms in a atfs-1 and ubl-5-dependent manner. Notably, metolazone failed to increase lifespan in worms with knocked-down nkcc-1. These results suggested that metolazone activates the UPR
mt
across species and prolongs the lifespan of C. elegans.
...
PMID:Metolazone upregulates mitochondrial chaperones and extends lifespan in Caenorhabditis elegans. 3321 50
