Desire :
Am J Pathol. 2007 Apr 19; [Epub
ahead of print] SRY-Related HMG ¡P
Sumi
E, Iehara
N, Akiyama H,
Matsubara T,
Mima
A, Kanamori
H, Fukatsu
A, Salant
DJ, Kita T, Arai H, Doi
T. From the Departments of Nephrology,* Orthopaedics, Cardiovascular Medicine, and Geriatric
Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan; the
Department of Medicine, Evans Biomedical Research Center, Boston
University Medical Center, Boston, Massachusetts; and the Department of
Clinical Biology and Medicine, Tokushima University School of Medicine,
Tokushima, Japan. Accumulation of alpha1(IV)
and alpha2(IV) collagen is one of the characteristic pathological changes
in glomerulosclerosis. Although the Col4a2 gene
is known to have a 0.3-kb critical enhancer element with the GAACAAT
motif, which transcription factor binds and transactivates
this motif has not been identified. In this study, we found that SRY-related
HMG PMID: 17446313 [PubMed -
as supplied by publisher] BMC
Cardiovasc Disord.
2007 Feb 26;7:6. Sry delivery to the adrenal medulla increases blood
pressure and adrenal medullary tyrosine hydroxylase of normotensive
WKY rats. ¡P
Ely D, Milsted
A, Bertram J,
Ciotti
M, Dunphy
G, Turner ME.
Department of Biology, BACKGROUND: Our laboratory has shown that a
locus on the SHR Y chromosome increases blood pressure (BP) in the SHR
rat and in WKY rats that had the SHR Y chromosome locus crossed into
their genome (SHR/y rat). A potential candidate for this Y chromosome
hypertension locus is Sry, a gene that encodes
a transcription factor that is responsible for testes development and the
Sry protein may affect other target genes.
METHODS: The following study examined if exogenous Sry
would elevate adrenal Th, adrenal catecholamines, plasma catecholamines
and blood pressure. We delivered 10 mug of either the
expression construct, Sry1/pcDNA 3.1, or control vector into the adrenal
medulla of WKY rats by electroporation. Blood
pressure was measured by the tail cuff technique and Th
and catecholamines by HPLC with electrochemical
detection. RESULTS: In the animals receiving Sry
there were significant increases after 3 weeks in resting plasma NE (57%)
and adrenal Th content (49%) compared to vector
controls. BP was 30 mmHg higher in Sry injected
animals (160 mmHg, p < .05) compared to vector controls (130 mmHg)
after 2-3 weeks. Histological analysis showed that the electroporation procedure did not produce
morphological damage. CONCLUSION: These results provide continued support
that Sry is a candidate gene for hypertension.
Also, these results are consistent with a role for Sry
in increasing BP by directly or indirectly activating sympathetic nervous
system activity. PMID: 17324261 [PubMed -
indexed for MEDLINE] Cytogenet Genome Res. 2007;116(3):232-4. Mapping platypus SOX
genes; autosomal location of SOX9 excludes it
from sex determining role. ¡P
Wallis MC,
Delbridge
ML, Pask
AJ, Alsop
AE, Grutzner
F, O'Brien PC,
Rens
W, Ferguson-Smith
MA, Graves JA.
Comparative Genomics Group, In the absence of an SRY orthologue
the platypus sex determining gene is unknown, so genes in the human
testis determining pathway are of particular interest as candidates. SOX9
is an attractive choice because SOX9 deletions cause male-to-female sex
reversal in humans and mice, and SOX9 duplications cause female-to-male
sex reversal. We have localized platypus SOX9, as well as the related
SOX10, to platypus chromosomes 15 and 10, respectively, the first
assignments to these platypus chromosomes, and the first comparative
mapping markers from human chromosomes 17 and 22. The autosomal
localization of platypus SOX9 in this study contradicts the hypothesis
that SOX9 acts as the sex determining switch in platypus. Copyright 2007
S. Karger AG, PMID: 17317965 [PubMed -
indexed for MEDLINE] N-terminal domain of the SRY protein. Herein,
we describe a young girl with pure gonadal dysgenesis and her father
carrying a novel familial mutation in the SRY gene at codon
number 3. This mutation is resulting in a serine (S) to leucine (L) substitution. The secondary structure of
the SRY protein was carried out by protein modelling
studies. This analysis suggests, with high possibility, that the
N-terminal domain of the SRY protein, where we found the mutation, could
form an alpha-helix from amino acid in position 2 to amino acid in
position 13. The secondary structure prediction and the chemical
properties of serine to leucine substitution stands for a potential disruption of this N-terminal
alpha-helix in the SRY protein. This mutation could have some role in
impeding the normal function of the SRY protein. PMID: 17063144 [PubMed -
indexed for MEDLINE] Cip1/Waf1/Kip1-2-family (p21(Cip1/Waf1),
p27(Kip1), p57(Kip2)) are shown both in the context of proliferation
regulators and as contributors to the apoptotic machinery. Bcl2-family
members (i.e. Bcl2, Bcl-X(L)
Mcl-1(L); Bax, Bok/Mtd,
Bak, and Bcl-X(S);
Bad, Bid, Bim(EL), Bmf,
Mcl-1(S)) are highlighted both for their apoptosis-regulating capacity
and also for their effect on the cell cycle progression. The PI3-K/Akt
cell survival pathway is shown as regulator of cell metabolism and cell
survival, but examples are also provided where aberrant activity of the
pathway may contribute to the induction of apoptosis. Myc/Mad/Max
proteins are shown both as a powerful S-phase driving complex and as
apoptosis-sensitizers. We also discuss multifunctional proteins like p53
and Rb (RBL1/p107, RBL2/p130) both in the
context of G(1)-S transition and as apoptotic
triggers. Finally, we reflect on novel therapeutic approaches that would
involve redirecting over-active survival and proliferation pathways
towards induction of apoptosis in cancer cells. PMID: 17303468 [PubMed -
as supplied by publisher
