Disposition characteristics of the macromolecular prodrug of mito mycin C (MM< '), mitomycin C-dextran conjugate (MMC-D), in normal and tumor (VX2 carcinoma)-bearing rabbit thigh muscles were studied using the in situ vascular perfusion technique. Three types of cationic MMC-D (MMC-D.,,) and two types of anionic MMC-D (MMC-D.,,) with different carrier molecular weights were used. After bolus ar...

OBJECTIVE Amifostine (AMI) has been used for the prevention of doxorubicin-induced cardiotoxicity in several experimental and a few clinical studies. The aim of this study was to investigate the effects of AMI on lipid peroxidation, protective enzymes, and mitoxantrone (MITO)-induced acute cardiotoxicity in the rat heart using biochemical tests and histopathological examinations. METHODS Thir...

Evidence for an intracellular renin-angiotensin system (RAS) in various cell organelles now includes the endoplasmic reticulum, nucleus, and mitochondria (Mito). Indeed, angiotensin (ANG) AT1 and AT2 receptor subtypes were functionally linked to Mito respiration and nitric oxide production, respectively, in previous studies. We undertook a biochemical analysis of the Mito RAS from male and fema...

It has long been known that the mitochondrial genome normally mutates at a higher rate than the nuclear genome. Direct estimates of mitochondrial mutation rates can be made by sequencing individuals from mutation-accumulation lines, for which the evolutionary timescale is known exactly. Using such an approach, estimates of mutation rates have been made for a small number of species (e.g. Denver...

Mitochondrial calcium plays a crucial role in mitochondrial metabolism, cell calcium handling, and cell death. However, some mechanisms concerning mitochondrial calcium regulation are still unknown, especially how mitochondrial calcium couples with cytosolic calcium. In this work, we constructed a novel mitochondrial calcium fluorescent indicator (mito-GCaMP2) by genetic manipulation. Mito-GCaM...

RATIONALE Mitochondrial [Ca(2+)] ([Ca(2+)](mito)) regulates mitochondrial energy production, provides transient Ca(2+) buffering under stress, and can be involved in cell death. Mitochondria are near the sarcoplasmic reticulum (SR) in cardiac myocytes, and evidence for crosstalk exists. However, quantitative measurements of [Ca(2+)](mito) are limited, and spatial [Ca(2+)](mito) gradients have n...

The mechanism(s) of intracellular sterol trafficking among subcellular organelle membranes is not well understood. Relative contributions of vesicular, sterol carrier protein, and membrane sterol domain pathways are not resolved. A sterol kinetic assay was used to resolve multiple sterol domains in microsome (MICRO), mitochondria (MITO), and plasma (PM) membrane: exchangeable, 20-40% of total; ...

The mammalian mitochondrial ribosomes (mitoribosomes) are responsible for synthesizing 13 membrane proteins that form essential components of the complexes involved in oxidative phosphorylation or ATP generation for the eukaryotic cell. The mammalian 55S mitoribosome contains significantly smaller rRNAs and a large mass of mitochondrial ribosomal proteins (MRPs), including large mito-specific a...

Many human diseases have been reported to be associated with mitochondrial dysfunction. Therefore, mitochondrial therapy would be expected to be useful and productive in the treatment of various diseases. To achieve such an innovative therapy, it will be necessary to deliver therapeutic agents into mitochondria. However, only a limited number of methods are available for accomplishing this. We ...