Modification of alterations in cardiac function and sarcoplasmic reticulum by vanadate in ischemic-reperfused rat hearts

Takeda, Satoshi; Mochizuki, Seibu; Saini, Harjot K.; Elimban, Vijayan; Dhalla, Naranjan S.

doi:10.1152/japplphysiol.00234.2005

Cited by 12 publications

(10 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite the fact that Pten is a known tumor suppressor [15], transient inhibition of Pten is being evaluated to treat other conditions. For example, there has already been work in developing agents that inhibit the activity of Pten to treat diabetes [33], provide cardiac protection against ischemia/reperfusion injury [34], reduce the severity of acute lung injury [35], and accelerate wound closure [36]. Some of these agents are commercially available, and it is crucial to note that such agents have already been used in mouse models with no evidence of deleterious effects.…”

Section: Discussionmentioning

confidence: 99%

Mice Lacking Pten in Osteoblasts Have Improved Intramembranous and Late Endochondral Fracture Healing

et al. 2013

View full text Add to dashboard Cite

The failure of an osseous fracture to heal (development of a non-union) is a common and debilitating clinical problem. Mice lacking the tumor suppressor Pten in osteoblasts have dramatic and progressive increases in bone volume and density throughout life. Since fracture healing is a recapitulation of bone development, we investigated the process of fracture healing in mice lacking Pten in osteoblasts (Ocn-cretg/+;Ptenflox/flox). Mid-diaphyseal femoral fractures induced in wild-type and Ocn-cretg/+;Ptenflox/flox mice were studied via micro-computed tomography (µCT) scans, biomechanical testing, histological and histomorphometric analysis, and protein expression analysis. Ocn-cretg/+;Ptenflox/flox mice had significantly stiffer and stronger intact bones relative to controls in all cohorts. They also had significantly stiffer healing bones at day 28 post-fracture (PF) and significantly stronger healing bones at days 14, 21, and 28 PF. At day 7 PF, the proximal and distal ends of the Pten mutant calluses were more ossified. By day 28 PF, Pten mutants had larger and more mineralized calluses. Pten mutants had improved intramembranous bone formation during healing originating from the periosteum. They also had improved endochondral bone formation later in the healing process, after mature osteoblasts are present in the callus. Our results indicate that the inhibition of Pten can improve fracture healing and that the local or short-term use of commercially available Pten-inhibiting agents may have clinical application for enhancing fracture healing.

show abstract

Section: Discussionmentioning

confidence: 99%

Mice Lacking Pten in Osteoblasts Have Improved Intramembranous and Late Endochondral Fracture Healing

et al. 2013

View full text Add to dashboard Cite

show abstract

“…In addition, marked alterations in different electrocardiographic parameters, including ST segment, QTc interval, number of premature ventricular contraction(PVC), and incidence of tachycardia as well as mortality, observed in animals at 1 day after occluding the coronary artery were attenuated by PLP ( Table 1 performance, isolated perfused hearts were subjected to 30 min of global ischemia followed by reperfusion for 30 min [ 46 ]. The results in Table 2 show that depressions in left ventricle developed pressure (LVDP), rate of pressure development ( + dP/dt), and rate of pressure decay (-dP/ dt) as well as increase in left ventricular end diastolic pressure due to I/R injury were reduced by PLP in a dosedependent manner.…”

Section: Cardioprotective Effects Of Vitamin B6 and Plp In Ischemic Hmentioning

confidence: 99%

“…The results in Table 2 show that depressions in left ventricle developed pressure (LVDP), rate of pressure development ( + dP/dt), and rate of pressure decay (-dP/ dt) as well as increase in left ventricular end diastolic pressure due to I/R injury were reduced by PLP in a dosedependent manner. Because the sarcoplasmic reticulum (SR), by virtue of its ability to regulate intracellular Ca 2 + , plays a central role in determining the status of cardiac contraction and relaxation [ 47 ], SR Ca -release activities of hearts subjected to I/R injury were examined [ 46 ] with or without PLP treatment. The results in Table 2 indicate that the I/R-induced defects in SR Ca 2 + transport were attenuated significantly by PLP treatment.…”

Section: Cardioprotective Effects Of Vitamin B6 and Plp In Ischemic Hmentioning

confidence: 99%

Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease

Dhalla

Takeda²,

Elimban

2013

Clinical Chemistry and Laboratory Medicine

Self Cite

View full text Add to dashboard Cite

Although vitamin B6 and its metabolite, pyridoxal 5 ′ -phosphate (PLP), have been shown to exert bene ficial effects in ischemic heart disease, the mechanisms of their action are not fully understood. Some studies have shown that ventricular arrhythmias and mortality upon the occlusion of coronary artery were attenuated by pretreatment of animals with PLP. Furthermore, ischemia-reperfusion-induced abnormalities in cardiac performance and defects in sarcoplasmic reticular Ca 2 + -transport activities were decreased by PLP. The increase in cardiac contractile activity of isolated heart by ATP was reduced by PLP, unlike propranolol, whereas that by isoproterenol was not depressed by PLP. ATP-induced increase in [Ca ] i in cardiomyocytes was depressed by PLP. Both high-and low-affinity sites for ATP binding in sarcolemmal membranes were also decreased by PLP. These observations support the view that PLP may produce cardioprotective effects in ischemic heart disease by attenuating the occurrence of intracellular Ca 2 + overload due to the blockade of purinergic receptors.

show abstract

“…In view of the strong oxidant property of peroxynitrite and the possibility of high concentrations of peroxynitrite present locally near the SL, SR and MF, it is possible that subcellular alterations in the I/R heart may be due to peroxynitrite-mediated oxidative stress. The role of oxidative stress in I/R-induced cardiac dysfunction is further supported by observations that some agents, such as vanadate and selenium, produce their beneficial effects on the I/R hearts by their antioxidant action [224,225]. Different mechanisms by which oxidative stress is considered to produce subcellular defects and cardiac dysfunction are indicated in Fig.…”

Section: Oxidative Stress and Subcellular Defects In I/r Heartsmentioning

confidence: 77%

Potential role and mechanisms of subcellular remodeling in cardiac dysfunction due to ischemic heart disease

Dhalla

Saini

Tappia

et al. 2007

Journal of Cardiovascular Medicine

View full text Add to dashboard Cite

Several studies have revealed varying degrees of changes in sarcoplasmic reticular and myofibrillar activities, protein content, gene expression and intracellular Ca-handling during cardiac dysfunction due to ischemia-reperfusion (I/R); however, relatively little is known about the sarcolemmal and mitochondrial alterations, as well as their mechanisms in the I/R hearts. Because I/R is associated with oxidative stress and intracellular Ca-overload, it has been indicated that changes in subcellular activities, protein content and gene expression due to I/R are related to both oxidative stress and Ca-overload. Intracellular Ca-overload appears to induce changes in subcellular activities, protein contents and gene expression (subcellular remodeling) by activation of proteases and phospholipases, as well as by affecting the genetic apparatus, whereas oxidative stress is considered to cause oxidation of functional groups of different subcellular proteins in addition to modifying the genetic machinery. Ischemic preconditioning, which is known to depress the development of both intracellular Ca-overload and oxidative stress due to I/R, was observed to attenuate the I/R-induced subcellular remodeling and improve cardiac performance. It is suggested that a combination therapy with antioxidants and interventions, which reduce the development of intracellular Ca-overload, may improve cardiac function by preventing or attenuating the occurrence of subcellular remodeling due to ischemic heart disease. It is proposed that defects in the activities of subcellular organelles may serve as underlying mechanisms for I/R-induced cardiac dysfunction under acute conditions, whereas subcellular remodeling due to alterations in gene expression may explain the impaired cardiac performance under chronic conditions of I/R.

show abstract

Modification of alterations in cardiac function and sarcoplasmic reticulum by vanadate in ischemic-reperfused rat hearts

Cited by 12 publications

References 36 publications

Mice Lacking Pten in Osteoblasts Have Improved Intramembranous and Late Endochondral Fracture Healing

Mice Lacking Pten in Osteoblasts Have Improved Intramembranous and Late Endochondral Fracture Healing

Mechanisms of the beneficial effects of vitamin B6 and pyridoxal 5-phosphate on cardiac performance in ischemic heart disease

Potential role and mechanisms of subcellular remodeling in cardiac dysfunction due to ischemic heart disease

Contact Info

Product

Resources

About