The development of the vertebrate lens utilizes a sophisticated cell-cell communication network via gap junction channels, which are made up of at least three connexin isoforms, α8 (Cx50), α3 (Cx46) and α1 (Cx43), and which are encoded by three different genes. In a previous study, we reported that, with a disruption of Gja3 (α3 connexin), mice developed nuclear cataracts with a normal sized lens. We show that Gja8tm1 (α8–/–) mice develop microphthalmia with small lenses and nuclear cataracts, while the α8 heterozygous (+/–) mice have relatively normal eyes and lenses. A comparative study of these α3 and α8 knockout mice showed that the protein levels of both α3 and α8 were independently regulated and there was no compensation for either the α3 or α8 protein from the wild-type allele when the other allele was disrupted. More interestingly, western blotting data indicated that the presence of α8 in the lens nucleus is dependent on α3 connexin, but not vice versa. The staining of the knock-in lacZ reporter gene showed the promoter activity of α8 connexin is much higher than that of α3 connexin in embryonic lenses and in adult lens epithelium. More importantly, a delayed denucleation process was observed in the interior fibers of the α8–/– lenses. Therefore, α8 connexin is required for proper fiber cell maturation and control of lens size.
Here, we report the draft genome sequence of
Nereida
sp. strain MMG025, isolated from the surface of giant kelp and assembled and analyzed by undergraduate students participating in a marine microbial genomics course. A genomic comparison suggests that MMG025 is a novel species, providing a resource for future microbiology and biotechnology investigations.
The aged heart is more susceptible to ischemic injury than the young heart. We hypothesized that loss of efficiency via reduced cellular scaffolds leads to this susceptibility. We examined the contribution of caveolin‐3 (Cav‐3), a lipid‐raft scaffolding protein, to ischemic tolerance in aged myocardium. Cav‐3 expression was reduced in aged hearts. Cardiac‐specific expression of Cav‐3 improved ischemic tolerance in both young (3 months) and aged (24 months) hearts. Aged WT hearts exhibited significant dysfunction, recovering only 20–25% of force and exhibiting almost 2‐fold higher diastolic pressure. Overexpression of Cav‐3 profoundly improved outcome in aged hearts with 60–65% recovery of pressure development and end diastolic pressure in the normal range. These data reveal a parallel decline in cardiac ischemic tolerance and Cav‐3 expression, and indicate that increasing Cav‐3 expression can eliminate age‐related ischemic intolerance. Cav‐3 may serve as a novel therapeutic target to limit dysfunction associated with cardiac aging.
Diabetes is a worldwide epidemic with cardiovascular disease being a major complication. Caveolins act as scaffolding molecules for regulating signaling. Overexpression of caveolin protects the heart from cardiovascular stress. We hypothesize that cardiac‐specific caveolin‐3 (Cav‐3) overexpression (OE) will protect the diabetic heart. Transgene negative (TGneg) or Cav‐3 OE mice were given a single dose of streptozotocin (75mg/kg) and then placed on a high fat diet to induce type II diabetes mellitus (T2DM). After 3 months, TGneg T2DM mice and Cav‐3 OE T2DM mice showed an increase in body weight, altered glucose tolerance response, and increased insulin levels compared to controls on normal diet. Cav‐3 OE T2DM mitochondria showed protection from calcium swelling and reactive oxygen species generation similar to controls, when compared to TGneg T2DM mitochondria. Cav‐3 OE controls and Cav‐3OE T2DM showed increased protein expression of OPA‐1 and Mitofusin 2, compared to TGneg controls and TGneg T2DM. Mitochondrial ultrastructure (i.e., mitochondrial swelling and clustering) was preserved in Cav‐3 OE T2DM hearts compared to TGneg T2DM. Our data suggest that Cav‐3 OE in the heart has the ability to limit injury in the setting of diabetes through regulation of mitochondrial structure and function.
Timothy syndrome (TS) is an extremely rare human disorder resulting from a single point mutation (G406R) in the intracellular part of the S6 transmembrane segment of domain 1 of Cav1.2. This region is encoded in a mutually exclusive manner by exons 8/8a.
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