Promotion of NAD+ recycling by the hypoxia-induced shift in the lactate dehydrogenase isozyme profile reduces the senescence of human bone marrow-derived endothelial progenitor cells.

Expansion of bone marrow-derived endothelial progenitor cells (EPCs) in vitro to obtain required cell numbers for therapeutic applications faces the challenge of growing cell senescence under the traditional normoxic culture condition. We previously found that 1% O2 hypoxic culture condition is favorable for reducing senescence of EPCs, but the mechanisms underlying the favorability are still unclear. Here, we found that, compared with normoxia, hypoxia induced a shift in lactate dehydrogenase (LDH) isozyme profile, which manifested as decreased LDH2 and LDH1 and increased LDH5, LDH4 and total LDHs. Moreover, under hypoxia, EPCs presented higher LDH activity, which could promote the conversion of pyruvate to lactate, as well as a higher level of NAD+, Bcl2 interacting protein 3 (BNIP3) expression and mitophagy. Additionally, under hypoxia, knock-down of the LDHA subunit increased the LDH2 and LDH1 levels and knock-down of the LDHB subunit increased the LDH5 level, while the simultaneous knock-down of LDHA and LDHB reduced total LDHs and NAD+ level. Inhibition of NAD+ recycling reduced BNIP3 expression and mitophagy and promoted cell senescence. Taken together, these data demonstrated that 1% O2 hypoxia induces a shift in the LDH isozyme profile, promotes NAD+ recycling, increases BNIP3 expression and mitophagy, and reduces EPC senescence. Our findings contribute to a better understanding of the connection between hypoxic culture conditions and the senescence of bone marrow-derived EPCs and provide a novel strategy to improve in vitro expansion of EPCs.

Relationship between the activity of serum lactate dehydrogenase(LDH) and serum vitamin C in Japanese men and women in their middle and old age / 日本農村医学会雑誌

The effects of the serum vitamin C levels on the activity and isozyme pattern of serum lactate dehydrogenase (LDH) in males and females in their middle and old age were examined.<BR>There was no siginificant correlation among the total serum, LDH activity and serum vitamin C levels in the 87 male and 83 female ranging from 45 to 84 years of age. However, high inverse correlations were found among the percentage of LDH-4 and LDH-5 and serum vitamin C levels all of age groups (45-59 years of age group, 60-69 years of age group and over 70 years of age group) of males and females.<BR>These results suggest that the percentage of LDH-4 and LDH-5 are influenced by the vitamin C intake in males and females in their middle and old age.

Epidemiological study on the relation of serum lactate dehydrogenase (LDH) isozymes and activity to protein intake in man / 日本農村医学会雑誌

This paper reports the changes in the activity and isozyme pattern of serum LDH in healthy young men given a low protein diet (0.73-0.75/kg body weight; 40-50g/day) for 21 days.<BR>Serum total LDH activity showed no significant change in eight healthy young volunteers who received low protein diet for 21 days. However, the percentages of LDH-5 and LDH-4 increased significantly (P<0.01) from basal levels of 5.9±2.3 and 7.1±1.4 to 10.6±2.9% and 10.1±0.9%, respectively on day 14.<BR>These results suggest that measurements of the percentages of LDH-4 and LDH-5 isozymes can be used to evaluate the protein intake, but serum LDH activity cannot be used as an index of nutrition.