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4‐Phenyl butyrate (4‐PBA) alters ERp29 expression, connexin localization and enhances mesenteric artery agonist‐induced constriction
Author(s) -
LooftWilson Robin Christine,
Smith Tekla,
Koval Michael,
Isakson Brant E
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.766.1
Subject(s) - vasoconstriction , mesenteric arteries , chemistry , phenylephrine , electrical impedance myography , constriction , endocrinology , vasodilation , medicine , endoplasmic reticulum , endothelium derived hyperpolarizing factor , connexin , gap junction , artery , intracellular , biochemistry , blood pressure
4‐PBA, an HDAC inhibitor and chemical chaperone, has therapeutic potential for many diseases. Based upon its known effect on protein processing and transport, we hypothesized that treatment of mesenteric arteries with 4‐PBA would alter the expression/distribution of gap junction proteins (connexins) and vasomotor function. Extra‐luminal 4‐PBA (2‐4 mM) treatment for 2 hr increased expression of ERp29, an endoplasmic reticulum chaperone that facilitates Cx43 transport, by ~50% (p<0.05). This coincided with a trend for increased total Cx40 and Cx43 protein, and increased localization of Cx37 to the endothelial cell membrane. Artery constriction (absolute and % diameter change; pressure myography) to phenylephrine (10 −5 M) was significantly greater (p<0.05) after 2 hr extra‐luminal 4‐PBA (2 mM) incubation, and compared to vehicle‐treated arteries, which constricted similarly before and after treatment. There were no significant differences in basal tone or dilation to acetylcholine (10 −5 M) before or after 4‐PBA or vehicle treatment, or between groups, indicating that increased vasoconstriction was not due to endothelial impairment. In conclusion, 4‐PBA alters connexin expression and localization. Whether these molecular changes contribute to the enhanced vasoconstriction remains to be determined. Support: NIH‐R15HL082647, R01HL083120, R01HL088554, AHA‐SDG.