ABSTRACT
Abstract The prolonged entry of large amounts of calcium into the mitochondria through the mitochondrial calcium uniporter complex (MCUC) may cause the permeability transition pore (mPTP) to open, which contributes to the pathogenesis of several diseases. Tissue-specific differences in mPTP opening due to variable expression of MCUC components may contribute to disease outcomes. We designed this study to determine differential mPTP opening in mitochondria isolated from different regions of mouse brain and kidney and to compare it with the expression of MCUC components. mPTP opening was measured using mitochondria isolated from the left/right brain hemispheres (LH/RH, respectively) and from kidney cortex/medulla, while the expression level of MCUC components was assessed from total cellular RNA. Interestingly, LH mitochondria showed less calcium-induced mPTP opening as compared to RH mitochondria at two different calcium concentrations. Conversely, mPTP opening was similar in the renal cortex and renal medulla mitochondria. However, the kidney mitochondria demonstrated bigger and faster mPTP opening as compared to the brain mitochondria. Furthermore, asymmetric mPTP opening in the LH and RH mitochondria was not associated with the expression of MCUC components. In brief, this study demonstrates thus far unreported asymmetric mPTP opening in mouse brain hemispheres that is not associated with the mRNA levels of MCUC components.
Subject(s)
Animals , Male , Female , Mice , Brain , Calcium/agonists , Cerebrum/abnormalities , Mitochondrial Permeability Transition Pore/analysis , Mice , Mitochondria , 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/adverse effects , Kidney CortexABSTRACT
Abstract Ligustrazine is widely used for the treatment of cardiovascular diseases in traditional Chinese medication. It has been reported that Ligustrazine decreases the concentration of intracellular calcium ions (Ca2+); however, the underlying mechanism remains unknown. In the present study, the effect of Ligustrazine on adenosine diphosphate (ADP)-induced platelet aggregation was evaluated using a turbidimetric approach. The changes in concentration of intracellular Ca2+ stimulated by ADP was measured using fluo-4, a fluorescent Ca2+ indicator dye. The mRNA expression of stromal interaction molecule l (STIM1) and Orai1, calcium sensor, was determined using real-time PCR. In addition, the protein expression of STIM1, Orai1, and serum/glucocorticoid-regulated protein kinase 1 (SGK1) was determined using Western blot analysis. The data demonstrated that Ligustrazine significantly suppressed platelet aggregation in a dose-dependent manner and reduced the concentration of intracellular Ca2+ triggered by ADP. Our data showed that Ligustrazine treatment inhibited the expression of STIM1 and Orai1 induced by ADP at both mRNA and protein levels, and suppressed the protein expression of SGK1. Taken together, our data indicated that Ligustrazine suppressed platelet aggregation by partly inhibiting the activities of calcium sensors, thereby suggesting that Ligustrazine may be a promising candidate for the treatment of platelet aggregation.
Subject(s)
Animals , Male , Rats , Protein Kinases , Cardiovascular Diseases/pathology , Platelet Aggregation , Adenosine Diphosphate/pharmacology , Blotting, Western/methods , Calcium/agonists , Asian People/classification , Stromal Interaction MoleculesSubject(s)
Humans , Male , Middle Aged , Coronary Vasospasm/diagnostic imaging , Angina Pectoris, Variant/diagnostic imaging , Angiography , Calcium/agonists , Coronary Vasospasm/physiopathology , Diagnosis, Differential , Isosorbide/therapeutic use , Angina Pectoris, Variant/physiopathology , Angina Pectoris, Variant/drug therapyABSTRACT
The present study was conducted to identify the modification carried out by both calcium agonist [Cacl2] and antagonist [VHcI] and inhibin like material [OTLP4] on the GnRH stimulated release of FSH and LH from male camel pituitary cell culture collected during breeding and non breeding seasons. The data obtained showed that 100 and 200 ul/ ml of GnRH was able to release both FSH and LH from pituitaries collected during the year. OTLP4 as an inhibin-like preparation was able to block FSH release from the pituitary especially during non breeding season. Calcium chloride pretreatment has a pronounced effect on LH release without any effect on FSH. The higher dose of calcium chloride unable to release LH from pituitaries collected during breeding season and it may be due to the calcium desensitizing effect. VHcl has a potent effect in blocking LH release to the media by all doses used. The blocking effect on FSH was obtained only when VHcI was used in a higher dose. The use of VHcl in the field for treatment of cardiovascular diseases and its effect on male reproduction need further in vivo investigation