PubMed · 2717855
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F J Gala León. 1989. [Suicide].. https://pubmed.ncbi.nlm.nih.gov/2717855/
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Intracellular protein degradation rates decrease with age in many tissues and organs. In cultured cells, chaperone-mediated autophagy, which is responsible for the selective degradation of cytosolic proteins in lysosomes, decreases with age. In this work we use lysosomes isolated from rat liver to analyze age-related changes in the levels and activities of the main components of chaperone-mediated autophagy. Lysosomes from "old" (22-month-old) rats show lower rates of chaperone-mediated autophagy, and both substrate binding to the lysosomal membrane and transport into lysosomes decline with age. A progressive age-related decrease in the levels of the lysosome-associated membrane protein type 2a that acts as a receptor for chaperone-mediated autophagy was responsible for decreased substrate binding in lysosomes from old rats as well as from late passage human fibroblasts. The cytosolic levels and activity of the 73-kDa heat-shock cognate protein required for substrate targeting to lysosomes were unchanged with age. The levels of lysosome-associated hsc73 were increased only in the oldest rats. This increase may be an attempt to compensate for reduced activity of the pathway with age.
We have investigated the age-dependent modifications in the expression of eight different subunits of the gamma-aminobutyric acid, type A (GABA(A)) receptor (alpha1, alpha2, alpha3, alpha5, beta2, beta3, gamma2S, and gamma2L) and all four subunits of the alpha-amino-3-hydroxy-5-methylsoxazole-4-propionate (AMPA) receptor (GluR1-4) in the hippocampus of 24-month-old rats. All aged hippocampi displayed a remarkable increase (aged/adult ratio, 3.53 +/- 0.54) in the mRNA levels of the short version of the gamma2 subunit in parallel with a similar increase in the gamma2 subunit protein (aged/adult ratio, 2.90 +/- 0.62). However, this increase was not observed in the mature receptor. On the other hand, the expression of the different alpha subunit mRNAs increased moderately with aging, displaying a heterogeneous pattern. The most frequent modification consisted in an increase in the expression of the alpha1 subunit mRNA (aged/adult ratio, 1.26 +/- 0.18), in parallel with a similar increase on the alpha1 protein (aged/adult ratio, 1. 27 +/- 0.12) and in the alpha1 incorporated to the assembled GABA(A) receptor (tested by immunoprecipitation; aged/adult ratio, = 1.20 +/- 0.10). However, in the same hippocampal samples, no major modifications were observed on the expression of the AMPA receptor subunits. As a whole, these results indicated the existence of an increased expression of the GABA(A) receptor subunits and a preservation of the AMPA receptor at the hippocampal formation. These modifications could reflect the existence of specific deficiencies (neuronal loss and/or deafferentiation) on the GABAergic system in the aged rats.
The muscles of the eyelids and the extraocular muscles of mysticete whales are poorly described for a variety of reasons, including considerable difficulty in obtaining specimens. Our objective is to provide such a description for the bowhead whale, Balaena mysticetus. This study has examined the gross anatomy of the region in six specimens (five adults, one fetus) of the bowhead whale. Results show that the muscles associated with the eye are well developed and possess several distinctive features. For example, precise limits of each extraocular muscle are difficult to determine along their entire length because these muscles intermingle with one another near their insertion. Furthermore, some fibers from these muscles (except the retractor bulbi) also insert into the eyelids. Pulling on these muscles to simulate contraction results in movement of the eyelids and suggests a role for these muscles in palpebral retraction. Insertion of a large levator palpebrae superioris muscle into the upper eyelid further enhances opening of the palpebral fissure. Another unusual feature is the presence of tunnel-like structures that redirect the dorsal and ventral oblique muscles. The dorsal oblique muscle is redirected caudally about 90 degrees, then directed medially by another 90 degrees. These directional changes are accomplished via a connective tissue tunnel derived in part from the fibrous connective tissue of the dorsal rectus and the levator palpebrae superioris muscles. In most terrestrial mammals, a similar change in direction is accomplished by a cartilaginous trochlea. The ventral oblique muscle originates via a slender tendon from the frontal bone and undergoes a similar radical change in direction. Its tendon of insertion undergoes about a 90-degree change in direction that is accomplished through a tunnel-like structure derived from fibrous connective tissue of the ventral rectus muscle. Based on the morphology of the musculature presented, it is likely that the eyeballs and eyelids of the bowhead whale are quite mobile and appear capable of complex movement. The possibility of retraction and protrusion of the eyeball is discussed.