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Endothelin‐B receptor mediates effect of intravitreal endothelin on mitochondria‐associated anterograde axonal transport
Author(s) -
Stokely M. E.,
Brady S. T.,
Yorio T.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.34_7.x
Subject(s) - axoplasmic transport , endothelin receptor , endocrinology , mitochondrion , medicine , retinal ganglion cell , receptor , endothelins , endothelin 1 , chemistry , optic nerve , endothelin 3 , biology , anatomy , biochemistry
Increased endothelins (ETs) are associated with glaucoma and have been proposed to contribute to development of glaucomatous optic neuropathy. In glaucoma, movement of anterogradely transported material important for ganglion cell survival is impaired, specifically transport of mitochondria. This study characterizes effect(s) of a single bolus of intravitreal endothelin (nonselective ET‐1, or ETb‐receptor selective ET‐3) on the mitochondrial subcomponent of anterograde axonal transport. Standard segmental analysis techniques were used to pulse‐label and analyze newly synthesized proteins undergoing anterograde axonal transport in optic nerves of male Sprague–Dawley rats ( n = 7; 35S‐methionine ± 2 nmols ET‐1 or ET‐3). Injection‐sacrifice intervals (ISIs) of 24, 28, 32, & 36 h were evaluated ( anova ). Effects of intravitreal ET‐1 are biphasic with maximal impact at times normally associated with mitochondrial protein transport (28–36 h). Total newly synthesized protein in the mitochondrial subcomponent was diminished by both ET‐1 treatment (28, 32, 36 h ISIs; p s = <0.001, 0.02, <0.001, respectively) and ET‐3 treatment (28 h, p < 0.01), with no difference between effects of ET‐1 and ET‐3 at 28 h ( p < 0.999). Data from 11 SDS–PAGE protein bands (139, 118, 89, 80, 64, 59, 51, 45, 42, 37, 25 kDa) in the mitochondrial subcomponent, indicate that ET‐1 both diminished (all p 's < 0.05) the amount of protein transported and consistently delayed appearance of labelled protein in the optic nerve by 4 h. These results are consistent with an ETB‐receptor mediated role for endothelins in the pathologic dysregulation of mitochondria‐associated anterograde axonal transport.