Biomedical subjects

G Y Koh

Publications and source records attributed to G Y Koh.

At least 37 records · Page 2Linked to original sources

PubMed2000

Coexistence of C-type natriuretic peptide and atrial natriuretic peptide systems in the bovine cornea.

PURPOSE: To determine whether the cornea synthesizes natriuretic peptides and contains their receptors. METHODS: The synthesis of the natriuretic peptides, C-type natriuretic peptide (CNP) and atrial natriuretic peptide (ANP), in the bovine cornea was determined by high-performance liquid chromatography (HPLC) with radioimmunoassay and Southern blot analysis. The presence of natriuretic peptide receptor (NPR)-A and -B and their localizations were measured by reverse transcription-polymerase chain reaction (RT-PCR), in vitro autoradiography, and the activation of particulate guanylyl cyclase by natriuretic peptides in the corneal membrane. RESULTS: The serial dilution curves of corneal extracts were parallel to the standard curves of CNP and ANP. With reversed-phase HPLC, a major immunoreactive peak of CNP or ANP was observed at the elution time corresponding with synthetic CNP(1-53) or atriopeptin III (APIII), respectively. The presence of mRNAs of CNP and ANP was also detected in the cornea by RT-PCR and/or Southern blot analysis. Production of 3',5'-cyclic guanosine monophosphate (cGMP) by the activation of particulate guanylyl cyclase in the corneal membrane was stimulated by ANP, BNP, and CNP. More cGMP was produced by CNP than by the other natriuretic peptides. Specific 125I-[Tyr0]-CNP(1-22) binding sites were localized in the endothelial cell layer of cornea. The apparent dissociation constant (Kd) value of the cornea was 3.06 +/- 0.73 nM and the maximum binding capacity was 3.40 +/- 0.63 femtomoles/mm2. Both NPR-A and NPR-B mRNAs were detected by RT-PCR. CONCLUSIONS: The cornea synthesizes CNP and ANP and contains their receptors. These results suggest that the CNP and ANP systems coexist in the bovine cornea.

Animals↗

PubMed1999

Molecular cloning, expression, and characterization of angiopoietin-related protein. angiopoietin-related protein induces endothelial cell sprouting.

Using degenerate polymerase chain reaction, we isolated a cDNA encoding a novel 493-amino acid protein from human and mouse adult heart cDNAs and have designated it angiopoietin-related protein-2 (ARP2). The NH(2)-terminal and COOH-terminal portions of ARP2 contain the characteristic coiled-coil domain and fibrinogen-like domain that are conserved in angiopoietins. ARP2 has two consensus glycosylation sites and a highly hydrophobic region at the NH(2) terminus that is typical of a secretory signal sequence. Recombinant ARP2 expressed in COS cells is secreted and glycosylated. In human adult tissues, ARP2 mRNA is most abundant in heart, small intestine, spleen, and stomach. In rat embryos, ARP2 mRNA is most abundant in the blood vessels and skeletal muscles. Endothelial and vascular smooth muscle cells also contain ARP2 mRNA. Recombinant ARP2 protein induces sprouting in vascular endothelial cells but does not bind to the Tie1 or Tie2 receptor. These results suggest that ARP2 may exert a function on endothelial cells through autocrine or paracrine action.

Amino Acid Sequence↗

PubMed1999

Angiopoietin-1 is an apoptosis survival factor for endothelial cells.

We examined the effect of angiopoietin-1 (Ang1) on apoptosis in human umbilical vein endothelial cells (HUVECs). Ang1 (5-1000 ng/ml) dose-dependently inhibited apoptosis under a serum-deprived state. A significant apoptotic inhibition occurred with as low as 50 ng/ml. Two hundred ng/ml of Ang1 inhibited to approximately 50% of the control apoptotic rates for 96 h. Furthermore, an augmented antiapoptotic effect of Ang1 by the addition of 20 ng/ml vascular endothelial growth factor was observed. This Ang1-induced strong antiapoptotic effect in endothelial cells is a novel and intriguing finding and could be an additional description of Ang1-induced direct biological function.

Angiopoietin-1↗

PubMed1999

Amplified CDK2 and cdc2 activities in primary colorectal carcinoma.

BACKGROUND: Cyclins are overexpressed in various malignancies, including carcinoma of the colorectum, esophagus, lung, larynx, and breast. However, to the authors' knowledge, the protein levels and activities of cyclin-dependent kinases (CDKs), which are the functional cyclin partners in the cell cycle, have not been investigated previously. METHODS: Eight samples of cancer tissue and adjacent normal tissue were taken from 23 patients with Stage B2-C1 (AJCC/UICC Stage II-III) colorectal carcinoma during curative resection. The protein levels of cyclin and CDKs were determined by Western blot analysis. The activities of CDKs were determined by the phosphorylation amount using specific substrates after immunoprecipitations. RESULTS: The protein expression of cyclin (D1, D3, E, and A) and CDKs (CDK4, CDK2, and cdc2) was higher in primary colorectal carcinoma tissue than in adjacent normal tissue. Whereas only 3 of 8 patients had increased CDK4 activity in cancer tissue, 8 of 8 and 7 of 8 patients had increased CDK2 and cdc2 activities, respectively, in cancer tissue compared with adjacent normal tissue. However, there were no positive correlations among the pathologic staging or differentiation status and the increased ratio of cyclin protein, CDK protein, or CDK activity. CONCLUSIONS: These results indicate that significant activation of S and M phases of the cell cycle occurs in primary colorectal carcinoma.

Aged↗

PubMed1999

Molecular cloning and characterization of a novel angiopoietin family protein, angiopoietin-3.

Using homology-based PCR, we have isolated cDNA encoding a novel member (491 amino acids) of the angiopoietin (Ang) family from human adult heart cDNA and have designated it angiopoietin-3 (Ang3). The NH2-terminal and COOH-terminal portions of Ang-3 contain the characteristic coiled-coil domain and fibrinogen-like domain that are conserved in other known Angs. Ang3 has a highly hydrophobic region at the N-terminus (approximately 21 amino acids) that is typical of a signal sequence for protein secretion. Ang3 mRNA is most abundant in adrenal gland, placenta, thyroid gland, heart and small intestine in human adult tissues. Additionally, Ang3 is a secretory protein, but is not a mitogen in endothelial cells.

Adult↗

PubMed1999

Gene-polymorphisms of angiotensin converting enzyme and endothelial nitric oxide synthase in patients with erectile dysfunction.

AIMS OF THE STUDY: Regulation of the penile smooth muscle tone and contractility is closely related to the activity of vasoactive substances, angiotensin II or nitric oxide. We investigated the relationship between gene polymorphism in the angiotensin converting enzyme (ACE) or endothelial nitric oxide synthase (ecNOS) and development of erectile dysfunction. METHODS: In 84 subjects with organic erectile dysfunction and 63 control subjects, gene polymorphisms in the ACE and ecNOS were determined by the polymerase chain reaction (PCR). RESULTS: The DD genotype of ACE was significantly (P < 0.01) more frequent in subjects with organic erectile dysfunction (54%) than in control subjects (24%). There was no significant difference in the distribution of the genotypes of ecNOS. CONCLUSION: The deletion polymorphism in the ACE gene, the DD genotype, as a marker of general vascular disease, may be seen more frequently in men with a diagnosis of vasculogenic erectile dysfunction.

Adult↗

PubMed1999

Differential changes of cell cycle regulators and activities in kidneys during pre- and postnatal development.

The present study was designed to determine the changes of the cyclin/CDK (cyclin dependent kinase)/CKI (CDK inhibitors) system in kidneys during pre- and postnatal development. All protein levels of cyclins (cyclins D1, D3, E, A, B) and protein levels and activities of CDKs (CDK4, CDK2, cdc2) were high in kidneys during the prenatal period and decreased differently during the postnatal period. As the phosphorylated active form of cyclin D1 decreased, the dephosphorylated inactive form of cyclin D1 increased during the early postnatal development. While CDK4 activities decreased markedly, the activities of CDK2 and cdc2 decreased gradually during the early postnatal period. While the p21(CIP1) protein was barely detectable during the prenatal period, but was not detectable during the postnatal period, the protein level of p27(KIP1) was detectable during pre- and postnatal periods. These results indicate that the cyclin/CDK/CKI system is actively involved in the nephrogenesis during the prenatal period and is closely associated with the withdrawal of the renal cell cycle during the postnatal period.

Age Factors↗

PubMed1998

Programmed changes of cell cycle regulators by serum deprivation regardless of skeletal myocyte differentiation.

Permanent withdrawal of skeletal myoblasts from the cell cycle precedes differentiation. We examined the changes of protein levels of cell cycle regulators and the activities of CDKs in differentiating (by serum deprivation) or in differentiation-inhibited (by serum deprivation + TGF-beta1 treated) C2C12 skeletal myocytes. Regardless of differentiation, protein levels of most cyclins declined over time while this effect was delayed slightly by TGF-beta1 for cyclins D1 and F. Although the protein levels of CDKs gradually decreased over time, the activities of CDK2 and cdc2 decreased dramatically between 0 and 12 h after serum deprivation in both groups. Decreased CDK2 and cdc2 activities were temporally related to decreased DNA synthesis. While the p27KIP1 protein increased in both groups, the p21CIP1 protein increased only in differentiating cells. In vivo, protein expressions of cyclins, CDKs, and p21CIP1 were high in fetal, but almost undetectable in adult skeletal muscle. In contrast, the levels of p27KIP1 protein in skeletal muscle were high throughout development. Thus, changes of cell cycle regulators in differentiating C2C12 myocytes paralleled those during skeletal muscle development of mice. These results suggest that the rapid reduction of DNA synthesis and activities of CDKs slow reduction of protein levels of cyclins and CDKs, and that the increase of p27KIP1 are programmed mechanisms upon mitogen deprivation regardless of differentiation in skeletal myocytes.

Animals↗

PubMed1998

Persistent and heterogenous expression of the cyclin-dependent kinase inhibitor, p27KIP1, in rat hearts during development.

We have previously shown that there were differential and dramatic decreases of cyclin and cyclin-dependent kinase (CDK) activities in cardiomyocytes during the neonatal period. The activity of CDKs control cell cycle progression, and this activity is regulated positively and negatively by association of CDKs with cyclins and cyclin-dependent kinase inhibitors (CKIs), respectively. While the INK family (p15(INK4B)/p16(INK4A)/p18(INK4C)/p19(INK4D)) of CKIs is not detectable in hearts, the KIP/CIP family (p21(CIP1), p27(KIP1) and p57(KIP2)) of CKIs is detectable in most organs including the heart. Differential and dramatic changes of the KIP/CIP family (p21(CIP1), p27(KIP1) and p57(KIP2)) of CKIs were detected in rat hearts during development. The mRNA and protein levels of p21(CIP1) and p57(KIP2) were readily detectable in hearts at gestational and early postnatal periods and decreased thereafter. The mRNA levels of p27(KIP1) in ventricles were high during the gestational period, and did not change until day 30 postnatal, then were decreased slightly in 90-day-old rats. The protein levels of p27(KIP1) increased significantly in the early postnatal period, then were expressed persistently, although levels decreased slightly in the adult period. However, protein levels of p27(KIP1) in atria did not change during development. Variable immuno-staining patterns of p27(KIP1) were observed at different periods of development and in various locations in myocardium. During the gestational period, approximately 35-50% of myocardial cells in the cardiac wall were p27(KIP1) immuno-positive and were distributed diffusely. These p27(KIP1) immunopositive cells increased predominantly in endocardial and mid-portion areas of ventricular myocardium at the early postnatal period. This heterogenous pattern of p27(KIP1) protein expression persisted to adult hearts though the percentage of p27(KIP1) immuno-positive cells decreased slightly. High magnification revealed that more than 50% of adult cardiomyocytes were p27(KIP1) immuno-positive and that p27(KIP1) was located solely in nuclei. These results indicate that p27(KIP1) may be an important inhibitor of CDK activities in cardiomyocytes during early postnatal development and may block the re-entrance of adult cardiomyocytes into the cell cycle after injury.

Animals↗

PubMed1998

Identification of alternatively spliced Na(+)-Ca2+ exchanger isoforms expressed in the heart.

Alternatively spliced isoforms of Na(+)-Ca2+ exchanger were found from various tissues and species. RT-PCR amplification was performed on the basis of our cloned mouse cardiac Na(+)-Ca2+ exchanger and four alternatively spliced isoforms of Na(+)-Ca2+ exchanger were identified. Three (NCX1.3, NCX1.4, and NCX1.12) of them were first identified in the heart, and one isoform (NCX1.12) was a novel spliced variant. These four spliced variants were present in the embryonic and adult atria and ventricles. Different cell types of the heart expressed different spliced isoforms of Na(+)-Ca2+ exchanger. Southern blot analysis indicated that the Na(+)-Ca2+ exchanger gene existed as a single copy in the mouse genome. Thus, the Na(+)-Ca2+ exchanger isoforms expressed in mouse heart are consistent with being produced by alternative splicing and they may have different functions in various cell types in the mouse heart.

Alternative Splicing↗

PubMed1998

Presence and biological activity of C-type natriuretic peptide-dependent guanylate cyclase-coupled receptor in the penile corpus cavernosum.

PURPOSE: To investigate the presence of C-type natriuretic peptide 1-22 (CNP)-dependent guanylyl cyclase (GC)-coupled receptor and its biological function in the penile erectile smooth muscle. MATERIALS AND METHODS: Experiments have been done in rabbit and rat to detect cyclic GMP (cGMP) generation by the activation of particulate GC by natriuretic peptides (NPs) in cavernosal membrane, to localize precise receptor using a quantitative in vitro autoradiography of the snap frozen sections, to define natriuretic peptide receptor (NPR) mRNA using a reverse transcriptase-polymerase chain reaction (RT-PCR) technique and to monitor changes of erectile smooth muscle tone by NPs in the penile tissue strips. RESULTS: Productions of cGMP by particulate GC in the corpus cavernosum membranes of rabbit and rat were stimulated by CNP, atrial natriuretic peptide 1-28 (ANP) and brain natriuretic peptide 1-26 (BNP) with a rank order of potency of CNP > BNP > ANP. HS-142-1, a selective antagonist for the GC-coupled NPR, inhibited the CNP-stimulated cGMP production in corpus cavernosal membrane of rabbit and rat. Specific 125I-(Tyr[0])-CNP bindings were localized in the corpus cavernosal smooth muscle of rabbit with Kd of 19.92+/-3.38 nM. and Bmax of 734.64+/-139.63 amol./mm2. B-subtype of NPR mRNA was detected in the penile corpus cavernosum of rat using RT-PCR technique. CNP relaxed the smooth muscle contracted by Nomega-nitro-L-arginine methylester (L-NAME). CONCLUSIONS: These results suggest for the first time that CNP modulates the erectile smooth muscle tone of penis by predominant activation of B-subtype of NPR with augmentation of cGMP production via particulate GC.

Animals↗

PubMed1998

Cell cycle regulators during human atrial development.

OBJECTIVES: The molecular mechanisms that regulate cardiomyocyte cell cycle and terminal differentiation in humans remain largely unknown. To determine which cyclins, cyclin dependent kinases (CDKs) and cyclin kinase inhibitors (CKIs) are important for cardiomyocyte proliferation, we have examined protein levels of cyclins, CDKs and CKIs during normal atrial development in humans. METHODS: Atrial tissues were obtained in the fetus from inevitable abortion and in the adult during surgery. Cyclin and CDK proteins were determined by Western blot analysis. CDK activities were determined by phosphorylation amount using specific substrate. RESULTS: Most cyclins and CDKs were high during the fetal period and their levels decreased at different rates during the adult period. While the protein levels of cyclin D1, cyclin D3, CDK4, CDK6 and CDK2 were still detectable in adult atria, the protein levels of cyclin E, cyclin A, cyclin B, cdc2 and PCNA were not detectable. Interestingly, p27KIP1 protein increased markedly in the adult period, while p21CIP1 protein in atria was detectable only in the fetal period. While the activities of CDK6, CDK2 and cdc2 decreased markedly, the activity of CDK4 did not change from the fetal period to the adult period. CONCLUSION: These findings indicate that marked reduction of protein levels and activities of cyclins and CDKs, and marked induction of p27KIP1 in atria, are associated with the withdrawal of cardiac cell cycle in adult humans.

Adult↗

PubMed1997

Cytoplasmic localization of cyclin D3 in seminiferous tubules during testicular development.

Using a newly developed polyclonal antibody against murine cyclin D3, we have found that protein levels of cyclin D3 were highly detectable only in thymus and testis in rats. Since testis offer unique opportunities to examine the cell cycle in vivo, we examined the temporal and spatial expression of cyclin D3 and the DNA synthesis indicator, proliferating cell nuclear antigen (PCNA), in the rat testis during development. The protein levels of cyclin D3 protein in testis from 7 days to 3 months old were almost constant and then decreased gradually thereafter. The protein levels of cyclin D1 and PCNA were high in the testis of 7- and 14-day-old rats and decreased during testicular development. In the seminiferous tubules of 7-day-old newborns, cyclin D3 was surprisingly located in cytoplasm of stem cells that had bigger nuclei than the nuclei of surrounding cells. Interestingly, cyclin D3 immunopositive cells did not immunostain with PCNA in nuclei. In the adult testis, anti-cyclin D3 antibody strongly stained the cytoplasm of early stage primary spermatocytes, lightly stained pachytene spermatocytes, but did not stain elongated spermatids. There was no detectable cyclin D3 in Sertoli cells, interstitial cells, or fibroblasts within seminiferous tubules, or in blood vessels within the interstitial matrix. The known cyclin D3 partner, cyclin dependent kinase 4, was located mainly in nuclei of spermatogonia and in early stage primary spermatocytes. Strong PCNA immunopositive staining was located in the nuclei of spermatogonia in adult testis. These results indicate that cyclin D3 is detectable in meiotically active male germ cells (PCNA-negative cells), but is conspicuously absent from mitotically active spermatogonia (PCNA-positive cells). Moreover, in contrast to in vitro reports, cyclin D3 is not located in the nucleus, but rather in the cytoplasm of male germ cells in vivo. Taken together, the presence of cyclin D3 in spermatocytes and its location in the cytoplasm lead us to speculate that cyclin D3 may have functions in male germ cells other than mitosis.

Aging↗

PubMed1997

Cyclins and cyclin dependent kinases during cardiac development.

The molecular mechanisms that regulate the cardiomyocyte cell cycle and its terminal differentiation remain largely unknown. To determine which cyclins or cyclin dependent kinases (CDKs) are important for cardiomyocyte proliferation, we examined the expression of cyclins and CDKs during normal cardiac development. All cyclins and CDKs were highly expressed during embryonic cardiac development, then they decreased at different rates after birth. The mRNAs and proteins of cyclins A and B (G2 and M phase cyclins) were found in embryonic and neonatal hearts, but were not detected in young or adult hearts. In contrast, while the mRNAs of cyclins D1, D2, D3, and E (G1 and S phase cyclins) were observed during all stages of development, the proteins of cyclins D1, D3, and E were observed in hearts at the young growth stage, although the levels decreased differently. Reverse transcriptase-polymerase chain reaction (RT-PCR) using specific cyclin B and D3 primers revealed that cyclins B and D3 originated from cardiomyocytes and noncardiomyocytes. The CDKs (cdc2, CDK2, and CDK4) were highly expressed during embryonic cardiac development and maintained almost constant levels during neonatal periods. However, they were expressed at very low levels at the young and adult stages. The pattern of proliferating cell nuclear antigen (PCNA) expression during cardiac development was similar to the expression of CDKs. These findings suggest that all cyclins and CDKs are involved in the cardiac cell cycle, and that marked and rapid reduction of mitotic cyclins may be associated with the withdrawal of the cardiac cell cycle after birth.

Animals↗

PubMed1997

Cyclin D1 overexpression promotes cardiomyocyte DNA synthesis and multinucleation in transgenic mice.

D-type cyclin/cyclin-dependent kinase (CDK) complexes regulate transit through the restriction point of the cell cycle, and thus are required for the initiation of DNA synthesis. Transgenic mice which overexpress cyclin D1 in the heart were produced to determine if D-type cyclin deregulation would alter myocardial development. Cyclin D1 overexpression resulted in a concomitant increase in CDK4 levels in the adult myocardium, as well as modest increases in proliferating cell nuclear antigen and CDK2 levels. Flow cytometric and morphologic analyses of dispersed cell preparations indicated that the adult transgenic cardiomyocytes had abnormal patterns of multinucleation. Histochemical analyses confirmed a marked increase in number of cardiomyocyte nuclei in sections prepared from the transgenic mice as compared with those from control animals. Tritiated thymidine incorporation analyses revealed sustained cardiomyocyte DNA synthesis in adult transgenic hearts.

Animals↗

PubMed1997

Differential and dramatic changes of cyclin-dependent kinase activities in cardiomyocytes during the neonatal period.

The molecular mechanisms that arrest cardiomyocytes in the cell cycle during the postnatal period remain largely unknown. We have examined changes of the expression of cyclins and CDKs, the activity of each CDK in cardiomyocytes during the postnatal period, and have compared those changes with rate of binucleation formation of cardiomyocytes in rats. The mRNA and protein levels of cyclin D1, A and B in cardiomyocytes were high at day 1, then the levels decreased at different rates during the postnatal period. While the protein levels of cyclin A and B rapidly decreased, the protein level of cyclin D1 was relatively constant. The protein levels of CDK4, CDK2, and cdc2 in cardiomyocytes were high at day 1, then their levels gradually decreased. However, the activity of CDK4, which is responsible for G1 phase of cell cycle, was detectable only at day 1. The activity of CDK2 activity, which is responsible for the S phase of cell cycle, was relatively high at day 1, decreased at day 2, abruptly decreased at day 4, maintained the same low level until day 10, and barely or not detectable thereafter in cardiomyocytes. The activity of cdc2 was high at day 1, increased by 20% at day 2, and then gradually decreased thereafter, although approximately 50% of maximum activity was present at day 6. Most cardiomyocytes were mononucleated during the first 2 days postnatal. The percentage of binucleated cardiomyocytes increased from 2.5% at day 2, 14% at day 4, 50% at day 8, 80% at day 14, and had reached adult levels at day 21 after birth. During active binucleation formation in neonatal (from days 1-14) cardiomyocytes, CDK4 or CDK2 was functionally negligible, while cdc2 was functionally active. These data suggest that there were differential and dramatic decrease of CDK4 and CDK2 activities in cardiomyocytes during neonatal period, and the functionally active cdc2 in neonatal cardiomyocytes may be involved in binucleation formation.

Animals↗

PubMed1997

Temporal expressions of cyclins and cyclin dependent kinases during renal development and compensatory growth.

The family of cyclins and cyclin-dependent kinases (CDKs) are important participants in the regulation of eukaryotic cell cycle. Our purpose was to examine temporal expressions of cyclins and CDKs during renal development and compensatory growth. During embryonic development the mRNA levels of all cyclins were high, and after birth their levels decreased at different rates. G2 and M phase cyclins, cyclin A and B, decreased immediately after birth. G1 and S phase cyclins, cyclins D1, D2, D3, and E, were observed during all stages of development and maintained almost constant levels until seven days after birth. They decreased thereafter and expressed very low levels during the adult period. The protein levels of cdc2, CDK2, and proliferating cell nuclear antigen (PCNA) were high during embryonic renal development and slowly decreased after birth. Their levels were very low during the youth and adult periods. Levels of CDK4 protein were high and did not change during renal development. Compensatory hypertrophic renal growth (CHRG) induced by unilateral nephrectomy (Unx) did not increase any cyclins, CDKs or PCNA. Subtotal nephrectomy (Snx) did not increase any cyclins or CDKs in remaining viable renal tissue (RVRT). However, Snx increased PCNA in RVRT. An immunohistochemical study revealed that PCNA was induced in a limited area adjacent to ischemic areas. Interestingly, Western blot analysis of protein extracts from RVRT showed the induction of a new 40 kDa protein that cross-reacted with the cyclin D3 antibody. These findings suggest that the marked reductions in mitotic cyclins may be associated with the withdrawal of renal cell cycle after birth. In addition, expressions of cyclins and CDKs did not change in the adult kidney during active phase of compensatory hypertrophic growth.

Animals↗

PubMed1997

Renal tubule regeneration after ischemic injury is coupled to the up-regulation and activation of cyclins and cyclin dependent kinases.

Proliferation of renal tubules after acute injury is a reactive process of renal regeneration for recovery of renal function. Molecular and cellular mechanisms of the re-entrance of renal cells into the cell cycle after injury remain largely unknown. We have measured the correlations among the extent of proliferative activity and expression of cyclins and CDKs, and activity of each CDK during the regeneration period in the outer medullae of kidneys after ischemic injury in rats. The ratio of proliferating cell nuclear antigen (PCNA) positively immuno-stained nuclei to total nuclei per each section of the outer medulla of kidney indicated the proliferative index (PI) for this study. PI in the control period was 0.1%. The PI was increased at day 1 (13.4%), remained at a plateau at days 3 and 5 (30.5 and 32.3%), and decreased at day 7 and day 14 (17.3 and 12.2%) after ischemic injury. Proliferative activity was readily detectable in renal tubules, but was hardly detectable in glomeruli or blood vessels. As the PI increased, the mRNA and protein levels of cyclins D1, D3 and B, the mRNA levels of cyclin A, the protein levels of CDK4 and CDK2, and the activities of CDKs (CDK4, CDK2 and cdc2) increased in the outer medullae of kidneys after ischemic injury. These findings suggest that the temporal induction of proliferative activity in outer medullary tubules was closely linked with the cyclin/CDK system for regeneration of kidney after ischemic injury.

Animals↗