Epithelial-to-mesenchymal transition (EMT) is an orchestrated event where epithelial cells progressively undergo biochemical changes and transition into mesenchymal-like cells by gradually losing their epithelial characteristics. EMT plays a crucial pathologic role in renal abnormalities, especi...

Our previous studies demonstrated that chronic systemic blockade of renin-angiotensin system (RAS) lowered blood pressure (BP) of Ren-2 transgenic rats (TGR) by the attenuation of both angiotensin II-dependent and sympathetic vasoconstriction. Since systemic RAS blockade also inhibits brain RAS,...

The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in the regulation of blood pressure and body fluid homeostasis and is a mainstay for the treatment of cardiovascular and renal diseases. Angiotensin II and aldosterone are the two most powerful biologically active products of t...

In steroid-producing cells, cholesterol transport from the outer to the inner mitochondrial membrane is the first and rate-limiting step for the synthesis of all steroid hormones. Cholesterol can be transported into mitochondria by specific mitochondrial protein carriers like the steroidogenic a...

Proliferation plays a critical role in tumor growth when cell migration is essential to invasion. The effect of Ang III and Ang II was evaluated on these important processes. Changes in the migration potential of prostate cancer cells were investigated using Wound Healing Test and a Transwell Mi...

Septic shock is a life threatening condition and a medical emergency. It is associated with organ dysfunction and hypotension despite optimal volume resuscitation. Refractory septic shock carries a very high rate of mortality and is associated with ischemic and arrhythmogenic complications from ...

Nowadays the adipose tissue is recognized as one of the most critical endocrine organs releasing many adipokines that regulate metabolism, inflammation and body homeostasis. There are several described adipokines, including the renin-angiotensin system (RAS) components that are especially activa...

Adrenodoxin (Adx) is a [2Fe–2S] ferredoxin involved in electron transfer reactions in the steroid hormone biosynthesis of mammals. In this study, we deleted the sequence coding for the complete interaction domain in the Adx cDNA. The expressed recombinant protein consists of the amino acids 1–...

Previously, we have proposed that bovine adrenocortical mitochondrial adrenodoxin reductase may possess a domain structure, based upon the generation of two major peptide fragments from limited tryptic proteolysis. In the present study, kinetic characterization of the NADPH-dependent ferricyanid...

Cortisol is an important intermediate for the production of steroidal drugs and can only be synthesized chemically by rather complicated multi-step procedures. The most critical step is the 11β-hydroxylation of 11-deoxycortisol, which is catalyzed by a mitochondrial enzyme, P-45011β. Various f...

SummaryAdrenodoxin is a component of the electron transfer system for mitochondrial cytochrome P450 in steroidogenic cells. To elucidate whether the steroidogenic state can modulate the amount and the distribution of adrenodoxin in the mitochondria, we determined immunohistochemically the distri...

Adrenodoxin is probably the best characterized member of the vertebrate-type [2Fe–2S]-cluster ferredoxins. It has been in the spotlight of scientific interest for many years due to its essential role in mammalian steroid hormone biosynthesis, where it acts as electron mediator between the NADPH...

Cytochrome P450 (P450) 27A1 catalyzes 27-hydroxylation of cholesterol and 25-hydroxylation of vitamin D3, serving as an important component for the maintenance of lipid homeostasis. In eukaryotic cells P450 27A1 is a membrane-bound protein located on the inner mitochondrial membrane and requires...

Adrenodoxin was purified from the rat adrenal gland. The A414A280 value of the purified rat adrenodoxin was 0.90 and the oxidized spectrum showed absorption maxima at 320, 414 and 455 nm, similar to those of bovine adrenodoxin. On SDS-PAGE, the rat adrenodoxin showed a single band with a molecul...

Excessive production of aldosterone has been implicated in the pathogenesis of hypertension and heart failure. One approach to ameliorate the deleterious effects of aldosterone is to suppress its biosynthesis. The enzyme aldosterone synthase (CYP11B2) is responsible for the final step of aldoste...

In this work, adrenodoxin (Adx) was expressed on the outer membrane of E. coli by autodisplay and then the iron–sulfur cluster was incorporated into apo-Adx by an anaerobic reconstitution process. For the determination of the redox potentials of the iron–sulfur clusters of the autodisplayed Ad...

Many biological functions involve the formation of protein-protein complexes. In the present study, we investigated the interaction of two proteins involved in electron transfer, adrenodoxin (Adx) and adrenodoxin reductase (AdR) by using Raman and infrared spectroscopies. Different shifts and sp...

Sibiromycin, an antitumour antibiotic forming a stable complex with the double-stranded DNA selectively inhibits the incorporation of [3H]thymidine into the H-strand of mtDNA during the incubation of isolated rat liver mitochondria in vitro. A model accounting for this result is presented. It is...

Anthramycin, tomaymycin and sibiromycin are pyrrolo(1,4)benzodiazepine antitumor antibiotics. These compounds react with DNA and other guanine-containing polydeoxynucleotides to form covalently bound antibiotic · polydeoxynucleotide complexes.Experiments utilizing radiolabelled antibiotics have...

A description of pyrrolo[1,4]benzodiazepine (PBD) biosynthesis is a prerequisite for engineering production of analogs with enhanced antitumor activity. Predicted dioxygenases Orf12 and SibV associated with dihydropyrrole biosynthesis in PBDs anthramycin and sibiromycin, respectively, were expre...